Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological pr...Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.展开更多
AIM： To generate a SV40Tag transgenic tumor animal model and to study the mechanism underlying tumorigenesis. METHODS： A mammary gland expression vector containing SV40Tag DNA was generated. Transgene fragments were...AIM： To generate a SV40Tag transgenic tumor animal model and to study the mechanism underlying tumorigenesis. METHODS： A mammary gland expression vector containing SV40Tag DNA was generated. Transgene fragments were microinjeted into fertilized eggs of FVB mice. The genetically manipulated embryos were transferred into the oviducts of pseudo-pregnant female mice. PCR and Northern blot analysis were used for genotype analysis of F1 and F2 mice. Transgene expression was detected by RT-PCR and immunohistochemistry. RESULTS： SV40Tag gene was detected in two lines of transgenic mice. One of them delivered the transgene to F1 and a tumor was found in the pancreas of these mice. RT-PCR and immunohistochemistry showed that SV40Tag gene was expressed in the tumor. Pathological characterization of the transgenic mice demonstrated that the tumor belonged to pancreatic cystic neoplasm. CONCLUSION： SV40Tag transgenic mouse model can be successfully established. The transgenic mice develop a pancreatic tumor, which can be used for investigation of the molecular mechanism of tumorigenesis in vivo.展开更多
Alzheimer's disease(AD) is an increasingly common neurodegenerative disease.Since the intestinal microbiome is closely related to nervous system diseases, alterations in the composition of intestinal microbiota co...Alzheimer's disease(AD) is an increasingly common neurodegenerative disease.Since the intestinal microbiome is closely related to nervous system diseases, alterations in the composition of intestinal microbiota could potentially contribute to the pathophysiology of AD. However, how the initial interactions with intestinal microbes alter events later in life, such as during neurodegenerative diseases, is still unclear. This review summarizes what is known about the relationship between the intestinal microbiome and AD.展开更多
Background: 24-dehydrocholesterol reductase(Dhcr24) catalyzes the last step of cholesterol biosynthesis, which is required for normal development and antiapoptotic activities of tissues. We found that Dhcr24 expressio...Background: 24-dehydrocholesterol reductase(Dhcr24) catalyzes the last step of cholesterol biosynthesis, which is required for normal development and antiapoptotic activities of tissues. We found that Dhcr24 expression decreased in the cTnTR141 Wdilated cardiomyopathy(DCM) transgenic mice. Therefore, we tested whether rescued expression of Dhcr24 could prevent the development of DCM and its possible mechanism.Methods: Heart tissue specific transgenic overexpression mice of Dhcr24 was generated, then was crossed to c TnTR141 Wmouse to obtain the double transgenic mouse(DTG). The phenotypes were demonstrated by the survival, cardiac geometry and function analysis, as well as microstructural and ultrastructural observations based on echocardiography and histology examination. The pathway and apoptosis were analysed by western blotting and TUNEL assay in vivo and in vitro.Results: We find that Dhcr24 decreased in hearts tissues of cTnTR141 Wand LMNAE82 KDCM mice. The transgenic overexpression of Dhcr24 significantly improves DCM phenotypes in cTnTR141 Wmice, and activates PI3K/Akt/HKII pathway, followed by a reduction of the translocation of Bax and release of cytochrome c, caspase-9 and caspase-3 activation and myocyte apoptosis. Knockdown the expression of Dhcr24 reduces the activation of PI3K/Akt/HKII pathway and inhibition of the mitochondrial-dependent apoptosis. The anti-apoptotic effect of Dhcr24 could be completely removed by the inhibition of PI3K pathway and partly removed by the HKII inhibitor in H9c2 cell line.Conclusion: Compensatory expression of Dhcr24 protect against DCM through activated PI3K/Akt/HKII pathway and reduce Bax translocation. This is the first investigation for the molecular mechanism of Dhcr24 participate in development of DCM.展开更多
Background: The time-related decline in regenerative capacity and organ homeostasis is a major feature of aging. Rehmannia glutinosa and Astragalus membranaceus have been used as traditional Chinese herbal medicines f...Background: The time-related decline in regenerative capacity and organ homeostasis is a major feature of aging. Rehmannia glutinosa and Astragalus membranaceus have been used as traditional Chinese herbal medicines for enhanced immunity and prolonged life. However, the mechanism by which this herbal medicine slows aging is unknown. In this study, we investigated the mechanism of the herbal anti-aging effect.Methods: Mice were fed diets supplemented with R. glutinosa or A. membranaceus for 10 months; the control group was fed a standard diet. The phenotypes were evaluated using a grading score system and survival analysis. The percentages of the senescence phenotypes of hematopoietic stem cells(HSCs) were determined by fluorescence-activated cell sorting analysis. The function and the mechanism of HSCs were analyzed by clonogenic assay and the real-time polymerase chain reaction.Results: The anti-aging effect of R. glutinosa is due to the enhanced function of HSCs. Mice fed with R. glutinosa displayed characteristics of a slowed aging process,including decreased senescence and increased rate of survival. Flow cytometry analysis showed decreased numbers of Lin–Sca1^+c-kit–(LSK) cells, long-term HSCs(LT-HSCs) and short-term HSCs(ST-HSCs) in the R. glutinosa group. In vitro, clonogenic assays showed increased self-renewal ability of LT-HSCs from the R. glutinosa group as well as maintaining LSK quiescence through upregulated p18 expression. The R. glutinosa group also showed decreased reactive oxygen species levels and the percentage of β-gal^+ cells through downregulation of the cellular senescence-associated protein p53 and p16.Conclusion: Rehmannia glutinosa exerts anti-aging effects by maintaining the quiescence and decreasing the senescence of HSCs.展开更多
AIM： To study the gene expression changes in pancreatic cystic neoplasm in SV40Tag transgenic mice model and to provide information about the prevention, clinical diagnosis and therapy of pancreatic cancer. METHODS：...AIM： To study the gene expression changes in pancreatic cystic neoplasm in SV40Tag transgenic mice model and to provide information about the prevention, clinical diagnosis and therapy of pancreatic cancer. METHODS： Using the pBC-SV40Tag transgenic mice model of pancreatic cystic neoplasm, we studied the gene expression changes by applying high-density microarrays. Validation of part gene expression profiling data was performed using real-time PCR.RESULTS： By using high-density oligonucleotide microarray, of 14113 genes, 453 were increased and 760 decreased in pancreatic cystic neoplasm, including oncogenes, cell-cycle-related genes, signal transduction-related genes, skeleton-related genes and metabolism-related genes. Among these, we confirmed the changes in Igf, Shh and Wnt signal pathways with real-time PCR. The results of real-time PCR showed similar expression changes in gene chip.CONCLUSION： all the altered expression genes are associated with cell cycle, DNA damage and repair, signal pathway, and metabolism. SV40Tag may cooperate with several proteins in promoting tumorigenesis.展开更多
Background： Murine model of coronary arterial inflammation has been widely accepted as an animal model of and used in Kawasaki disease （KD）. This study sought to evaluate the developmental changes of coronary arter...Background： Murine model of coronary arterial inflammation has been widely accepted as an animal model of and used in Kawasaki disease （KD）. This study sought to evaluate the developmental changes of coronary arteries and cardiac function in a murine model of KD with a high-frequency ultrasound system and to provide evidence for the preparation of the model of KD. Methods： Lactobacillus case~ cell wall extract was prepared and injected into C57BL/6 mice intraperitoneally （i.p.） to induce KD. A total of 120 mice were grouped into three groups. The intravenous immunoglobulin （IVIG） treatment group was i.p. injected with IVIG （2 g/kg）, while the KD model and normal control groups were i.p. injected with 0.5 ml of phosphate buffered solution on day 5. All high-resolution echocardiography detection of mouse heart was performed by the same senior technician. Animal echocardiography was performed by measuring the coronary artery dimensions and cardiac function on days 0, 7, 14, 28, and 56 （high-resolution small animal ultrasound [Vevo770 pattem; VisualSonic, Canada] with broadband probe [RMVTM707B; frequency, 30 mHz; depth of focus, 1.2 cm]） which were measured and analyzed with Vevo770 software. Results： Pathological studies revealed focal inflammatory infiltrate asymmetrically distributed around the coronary artery trunk in the KD model group. Echocardiographic study including coronary dimension and cardiac function measurements was successfully performed in all subjects. The KD model and IVIG treatment groups showed left coronary artery dilation on days 7, 14, 28, and 56. The diameter of left coronary artery in the KD model group （0.53 ± 0.09 mm; 0.36 ± 0.07 mm; 0.34 ±0.05 mm; 0.34±0.04 mm） was significantly larger than those of 1VIG treatment group （0.22± 0.02 mm; 0.28 ± 0.03 mm; 0.26± 0.03 mm; 0.27 ±0.05 mm; 0.26 ± 0.03 mm; all P〈 0.01） and the normal control group （0.21 ±0.02 mm; 0.22 ±0.03 mm; 0.22± 0.02 mm; 0.23 ± 0.02 mm; 0.27± 0.04 mm; all P 〈 0.01） on days 7, 14, 28, and 56. No significant differences were observed in the measurements of cardiac fimction among the groups on days 0, 7, 14, 28, and 56 （all P〉 0.05）. Conclusions： Echocardiography could identify the consecutive changes of coronary artery in KD mice. Echocardiography is more convenient and direct in evaluating the coronary abnormalities in this animal model.展开更多
Background： Myocardial infarction （MI） is a major disease burden. Wild-type p53-induced phosphatase 1 （Wipl） has been studied extensively in the context of cancer and the regulation of different types of stem cel...Background： Myocardial infarction （MI） is a major disease burden. Wild-type p53-induced phosphatase 1 （Wipl） has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wipl in cardiac adaptation to M I is unknown. We investigated the significance of Wipl in a mouse model of MI. Methods： The study began in June 2014 and was completed in July 2016. We compared Wipl-knockout （Wipl-KO） mice and wild-type （WT） mice to deternline changes in cardiac function and survival in response to MI. The heart weight/body weight （HW/BW） ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending （LAD） coronary artery under 1.5% isoflurane anesthesia. After M1, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin （H＆E） staining was used to determine the infarct size. Gene expression of interleukin-6 （IL-6）, turnor necrosis factor-α （TNF-α）, and interleukin-1β （IL-1β） was assessed by quantitative real-time polymerase chain reaction （qPCR）, and the levels of signal transducers and activators of transcription 3 （stat3） and phosphor-stat3 （p-stat3） were also analyzed by Western blotting. Kaplan-Meier survival analysis, log-rank test, unpaired l-test, and one-way analysis of variance （ANOVA） were used for statistical analyses. Results： Wipl-KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac fiinction before LAD ligation. Alter MI, Wipl-deficient mice exhibited increased mortality （57.14% vs. 29.17%; n = 24 [WT], n - 35 [WipI-KO], P 〈 0.05）, increased cardiac hypertrophy （HW/BW ratio： 7 days： 7.25±0.36 vs. 5.84 ± 0.18, n cross-sectional area： 7 days： 311.80 ± 8.29 vs. 268.90 ± 11.15, n P 〉 0.05）, and reduced cardiac function （ejection fraction： 7 days 10, p〈 0.01, and 4 weeks： 6.05± 0.17 vs. 5.87 ±0.24, n= 10, P〉0.05; P 〈 0.05, and 4 weeks： 308.80 ± 11.26 vs. 317.00 ±13.55, n = 6 29.37± 1.38 vs. 34.72 ± 1.81, P 〈 0.05, and 4 weeks： 19.06 ± 2.07 vs 26.37 ± 2.95, P〈 0.05; fractional shortening： 7 days： 13.72 ± 0.71 vs. 16.50 ± 0.94, P〈 0.05, and 4 weeks： 8.79 ±1.00 vs. 12.48 ±1.48, P 〈 0.05; n = l0 [WT], n = 15 [Wipl-KO]）. H＆E staining revealed a larger infarct size in Wipl-KO mice than in WT mice （34.79% ± 2.44% vs. 19.55% ± 1.48%, n = 6, P 〈 0.01 ）. The expression oflL-6 and p-stat3 was downregulated in Wipl-KO mice （IL-6：1.71 ± 0.27 vs. 4.46 ± 0.79, n = 6, P 〈 0.01 ; and p-stat3/stat3：1.15 ±0.15 vs. 1.97 ± 0.23, n = 6, P 〈 0.05）. Conclusion： The results suggest that Wipl could protect the heart from MI-induced ischemic injury.展开更多
Background Cholecystokinin （CCK） is one of the richest neuropeptides in the mammalian brain, which is mainly distributed in the cerebral cortex, hippocampus, thalamus and caudate-putamen. CCK is implicated in a vari...Background Cholecystokinin （CCK） is one of the richest neuropeptides in the mammalian brain, which is mainly distributed in the cerebral cortex, hippocampus, thalamus and caudate-putamen. CCK is implicated in a variety of behavioral functions such as food intake, learning, memory, anxiety, pain and neuroprotection. The current research results for CCK are obtained mainly through injection of CCK peptide into the body. The key issues of whether CCK can regulate diet by a central pathway and whether there are long-term regulation effects on diet are still unresolved. In this study, the effects of CCK on food intake in transgenic mice were investigated. Methods Transgenic mice were created by microinjection of the PDGF-CCK construct into male pronucleus of the zygotes. The genomic phonetype of transgenic mice were identified by PCR. The expression of PDGF-CCK was analyzed by Western blotting. Body weight, plasma glucose, cholesterol and triglycerides were assayed and analyzed. Results Two PDGF-CCK transgenic independent lines were established and exhibited a high-levels brain-specific transgene expression compared with that of nontransgenic littermate controls. The food intake of male CCK transgenic mice was decreased by 5%-10% with the same levels of water consumed compared with wild type mice. The food intake in female mice was not obviously changed. In the transgenic mice the bodyweight was lower and plasma glucose was higher compared with the nontransgenic littermate controls. Conclusions The high expression of the CCK gene in the brain can decrease body weight and increase plasma glucose. The differences in food intake between the males and females require further study. Chin Med J 2009; 122（17）：2022-2026展开更多
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2017-I2M-2-005 and 2016-I2M-2-006Beijing Natural Science Foundation,Grant/Award Number:5171001
文摘Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.
基金Supported by the National Key Technologies Research and Development Program of China during The 10th Five-Year Plan Period, No2001BA70113.
文摘AIM： To generate a SV40Tag transgenic tumor animal model and to study the mechanism underlying tumorigenesis. METHODS： A mammary gland expression vector containing SV40Tag DNA was generated. Transgene fragments were microinjeted into fertilized eggs of FVB mice. The genetically manipulated embryos were transferred into the oviducts of pseudo-pregnant female mice. PCR and Northern blot analysis were used for genotype analysis of F1 and F2 mice. Transgene expression was detected by RT-PCR and immunohistochemistry. RESULTS： SV40Tag gene was detected in two lines of transgenic mice. One of them delivered the transgene to F1 and a tumor was found in the pancreas of these mice. RT-PCR and immunohistochemistry showed that SV40Tag gene was expressed in the tumor. Pathological characterization of the transgenic mice demonstrated that the tumor belonged to pancreatic cystic neoplasm. CONCLUSION： SV40Tag transgenic mouse model can be successfully established. The transgenic mice develop a pancreatic tumor, which can be used for investigation of the molecular mechanism of tumorigenesis in vivo.
基金CAMS Innovation Fund for Medical Science,Grant/Award Number:2016-12M-1-010,2017-12M-2-005National Science Fund for Young Scholars,Grant/Award Number:81500938International Science and Technology Cooperation Program of China,Grant/Award Number:2015DFG32230
文摘Alzheimer's disease(AD) is an increasingly common neurodegenerative disease.Since the intestinal microbiome is closely related to nervous system diseases, alterations in the composition of intestinal microbiota could potentially contribute to the pathophysiology of AD. However, how the initial interactions with intestinal microbes alter events later in life, such as during neurodegenerative diseases, is still unclear. This review summarizes what is known about the relationship between the intestinal microbiome and AD.
基金The present work was supported by the National Science and Technology Support Project(2015BAI08B01)CAMS Innovation Fund for Medical Sciences(CAMS-I2M,2016-I2M-1-015)Beijing Natural Science Foundation(5172027)
文摘Background: 24-dehydrocholesterol reductase(Dhcr24) catalyzes the last step of cholesterol biosynthesis, which is required for normal development and antiapoptotic activities of tissues. We found that Dhcr24 expression decreased in the cTnTR141 Wdilated cardiomyopathy(DCM) transgenic mice. Therefore, we tested whether rescued expression of Dhcr24 could prevent the development of DCM and its possible mechanism.Methods: Heart tissue specific transgenic overexpression mice of Dhcr24 was generated, then was crossed to c TnTR141 Wmouse to obtain the double transgenic mouse(DTG). The phenotypes were demonstrated by the survival, cardiac geometry and function analysis, as well as microstructural and ultrastructural observations based on echocardiography and histology examination. The pathway and apoptosis were analysed by western blotting and TUNEL assay in vivo and in vitro.Results: We find that Dhcr24 decreased in hearts tissues of cTnTR141 Wand LMNAE82 KDCM mice. The transgenic overexpression of Dhcr24 significantly improves DCM phenotypes in cTnTR141 Wmice, and activates PI3K/Akt/HKII pathway, followed by a reduction of the translocation of Bax and release of cytochrome c, caspase-9 and caspase-3 activation and myocyte apoptosis. Knockdown the expression of Dhcr24 reduces the activation of PI3K/Akt/HKII pathway and inhibition of the mitochondrial-dependent apoptosis. The anti-apoptotic effect of Dhcr24 could be completely removed by the inhibition of PI3K pathway and partly removed by the HKII inhibitor in H9c2 cell line.Conclusion: Compensatory expression of Dhcr24 protect against DCM through activated PI3K/Akt/HKII pathway and reduce Bax translocation. This is the first investigation for the molecular mechanism of Dhcr24 participate in development of DCM.
基金National Science Foundation for China,Grant/Award Number:31672374PUMC Youth Fund,Grant/Award Number:2017310018CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2016-12M-1-012
文摘Background: The time-related decline in regenerative capacity and organ homeostasis is a major feature of aging. Rehmannia glutinosa and Astragalus membranaceus have been used as traditional Chinese herbal medicines for enhanced immunity and prolonged life. However, the mechanism by which this herbal medicine slows aging is unknown. In this study, we investigated the mechanism of the herbal anti-aging effect.Methods: Mice were fed diets supplemented with R. glutinosa or A. membranaceus for 10 months; the control group was fed a standard diet. The phenotypes were evaluated using a grading score system and survival analysis. The percentages of the senescence phenotypes of hematopoietic stem cells(HSCs) were determined by fluorescence-activated cell sorting analysis. The function and the mechanism of HSCs were analyzed by clonogenic assay and the real-time polymerase chain reaction.Results: The anti-aging effect of R. glutinosa is due to the enhanced function of HSCs. Mice fed with R. glutinosa displayed characteristics of a slowed aging process,including decreased senescence and increased rate of survival. Flow cytometry analysis showed decreased numbers of Lin–Sca1^+c-kit–(LSK) cells, long-term HSCs(LT-HSCs) and short-term HSCs(ST-HSCs) in the R. glutinosa group. In vitro, clonogenic assays showed increased self-renewal ability of LT-HSCs from the R. glutinosa group as well as maintaining LSK quiescence through upregulated p18 expression. The R. glutinosa group also showed decreased reactive oxygen species levels and the percentage of β-gal^+ cells through downregulation of the cellular senescence-associated protein p53 and p16.Conclusion: Rehmannia glutinosa exerts anti-aging effects by maintaining the quiescence and decreasing the senescence of HSCs.
基金Supported by the National Key Technologies Research and Development Program of China during the 10th Five-Year Plan Period, No. 2001BA70113
文摘AIM： To study the gene expression changes in pancreatic cystic neoplasm in SV40Tag transgenic mice model and to provide information about the prevention, clinical diagnosis and therapy of pancreatic cancer. METHODS： Using the pBC-SV40Tag transgenic mice model of pancreatic cystic neoplasm, we studied the gene expression changes by applying high-density microarrays. Validation of part gene expression profiling data was performed using real-time PCR.RESULTS： By using high-density oligonucleotide microarray, of 14113 genes, 453 were increased and 760 decreased in pancreatic cystic neoplasm, including oncogenes, cell-cycle-related genes, signal transduction-related genes, skeleton-related genes and metabolism-related genes. Among these, we confirmed the changes in Igf, Shh and Wnt signal pathways with real-time PCR. The results of real-time PCR showed similar expression changes in gene chip.CONCLUSION： all the altered expression genes are associated with cell cycle, DNA damage and repair, signal pathway, and metabolism. SV40Tag may cooperate with several proteins in promoting tumorigenesis.
文摘Background： Murine model of coronary arterial inflammation has been widely accepted as an animal model of and used in Kawasaki disease （KD）. This study sought to evaluate the developmental changes of coronary arteries and cardiac function in a murine model of KD with a high-frequency ultrasound system and to provide evidence for the preparation of the model of KD. Methods： Lactobacillus case~ cell wall extract was prepared and injected into C57BL/6 mice intraperitoneally （i.p.） to induce KD. A total of 120 mice were grouped into three groups. The intravenous immunoglobulin （IVIG） treatment group was i.p. injected with IVIG （2 g/kg）, while the KD model and normal control groups were i.p. injected with 0.5 ml of phosphate buffered solution on day 5. All high-resolution echocardiography detection of mouse heart was performed by the same senior technician. Animal echocardiography was performed by measuring the coronary artery dimensions and cardiac function on days 0, 7, 14, 28, and 56 （high-resolution small animal ultrasound [Vevo770 pattem; VisualSonic, Canada] with broadband probe [RMVTM707B; frequency, 30 mHz; depth of focus, 1.2 cm]） which were measured and analyzed with Vevo770 software. Results： Pathological studies revealed focal inflammatory infiltrate asymmetrically distributed around the coronary artery trunk in the KD model group. Echocardiographic study including coronary dimension and cardiac function measurements was successfully performed in all subjects. The KD model and IVIG treatment groups showed left coronary artery dilation on days 7, 14, 28, and 56. The diameter of left coronary artery in the KD model group （0.53 ± 0.09 mm; 0.36 ± 0.07 mm; 0.34 ±0.05 mm; 0.34±0.04 mm） was significantly larger than those of 1VIG treatment group （0.22± 0.02 mm; 0.28 ± 0.03 mm; 0.26± 0.03 mm; 0.27 ±0.05 mm; 0.26 ± 0.03 mm; all P〈 0.01） and the normal control group （0.21 ±0.02 mm; 0.22 ±0.03 mm; 0.22± 0.02 mm; 0.23 ± 0.02 mm; 0.27± 0.04 mm; all P 〈 0.01） on days 7, 14, 28, and 56. No significant differences were observed in the measurements of cardiac fimction among the groups on days 0, 7, 14, 28, and 56 （all P〉 0.05）. Conclusions： Echocardiography could identify the consecutive changes of coronary artery in KD mice. Echocardiography is more convenient and direct in evaluating the coronary abnormalities in this animal model.
文摘Background： Myocardial infarction （MI） is a major disease burden. Wild-type p53-induced phosphatase 1 （Wipl） has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wipl in cardiac adaptation to M I is unknown. We investigated the significance of Wipl in a mouse model of MI. Methods： The study began in June 2014 and was completed in July 2016. We compared Wipl-knockout （Wipl-KO） mice and wild-type （WT） mice to deternline changes in cardiac function and survival in response to MI. The heart weight/body weight （HW/BW） ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending （LAD） coronary artery under 1.5% isoflurane anesthesia. After M1, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin （H＆E） staining was used to determine the infarct size. Gene expression of interleukin-6 （IL-6）, turnor necrosis factor-α （TNF-α）, and interleukin-1β （IL-1β） was assessed by quantitative real-time polymerase chain reaction （qPCR）, and the levels of signal transducers and activators of transcription 3 （stat3） and phosphor-stat3 （p-stat3） were also analyzed by Western blotting. Kaplan-Meier survival analysis, log-rank test, unpaired l-test, and one-way analysis of variance （ANOVA） were used for statistical analyses. Results： Wipl-KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac fiinction before LAD ligation. Alter MI, Wipl-deficient mice exhibited increased mortality （57.14% vs. 29.17%; n = 24 [WT], n - 35 [WipI-KO], P 〈 0.05）, increased cardiac hypertrophy （HW/BW ratio： 7 days： 7.25±0.36 vs. 5.84 ± 0.18, n cross-sectional area： 7 days： 311.80 ± 8.29 vs. 268.90 ± 11.15, n P 〉 0.05）, and reduced cardiac function （ejection fraction： 7 days 10, p〈 0.01, and 4 weeks： 6.05± 0.17 vs. 5.87 ±0.24, n= 10, P〉0.05; P 〈 0.05, and 4 weeks： 308.80 ± 11.26 vs. 317.00 ±13.55, n = 6 29.37± 1.38 vs. 34.72 ± 1.81, P 〈 0.05, and 4 weeks： 19.06 ± 2.07 vs 26.37 ± 2.95, P〈 0.05; fractional shortening： 7 days： 13.72 ± 0.71 vs. 16.50 ± 0.94, P〈 0.05, and 4 weeks： 8.79 ±1.00 vs. 12.48 ±1.48, P 〈 0.05; n = l0 [WT], n = 15 [Wipl-KO]）. H＆E staining revealed a larger infarct size in Wipl-KO mice than in WT mice （34.79% ± 2.44% vs. 19.55% ± 1.48%, n = 6, P 〈 0.01 ）. The expression oflL-6 and p-stat3 was downregulated in Wipl-KO mice （IL-6：1.71 ± 0.27 vs. 4.46 ± 0.79, n = 6, P 〈 0.01 ; and p-stat3/stat3：1.15 ±0.15 vs. 1.97 ± 0.23, n = 6, P 〈 0.05）. Conclusion： The results suggest that Wipl could protect the heart from MI-induced ischemic injury.
文摘Background Cholecystokinin （CCK） is one of the richest neuropeptides in the mammalian brain, which is mainly distributed in the cerebral cortex, hippocampus, thalamus and caudate-putamen. CCK is implicated in a variety of behavioral functions such as food intake, learning, memory, anxiety, pain and neuroprotection. The current research results for CCK are obtained mainly through injection of CCK peptide into the body. The key issues of whether CCK can regulate diet by a central pathway and whether there are long-term regulation effects on diet are still unresolved. In this study, the effects of CCK on food intake in transgenic mice were investigated. Methods Transgenic mice were created by microinjection of the PDGF-CCK construct into male pronucleus of the zygotes. The genomic phonetype of transgenic mice were identified by PCR. The expression of PDGF-CCK was analyzed by Western blotting. Body weight, plasma glucose, cholesterol and triglycerides were assayed and analyzed. Results Two PDGF-CCK transgenic independent lines were established and exhibited a high-levels brain-specific transgene expression compared with that of nontransgenic littermate controls. The food intake of male CCK transgenic mice was decreased by 5%-10% with the same levels of water consumed compared with wild type mice. The food intake in female mice was not obviously changed. In the transgenic mice the bodyweight was lower and plasma glucose was higher compared with the nontransgenic littermate controls. Conclusions The high expression of the CCK gene in the brain can decrease body weight and increase plasma glucose. The differences in food intake between the males and females require further study. Chin Med J 2009; 122（17）：2022-2026
