Background:Heat and Blood Stasis Syndrome(HBSS),a syndrome in traditional Chinese medicine is intrinsically linked to vascular endothelial injury.Taohe Chengqi Decoction(THCQT)is considered to treat diseases related t...Background:Heat and Blood Stasis Syndrome(HBSS),a syndrome in traditional Chinese medicine is intrinsically linked to vascular endothelial injury.Taohe Chengqi Decoction(THCQT)is considered to treat diseases related to HBSS by improving inflammatory response,oxidative stress,and blood circulation disorder.This study aimed to elucidate the therapeutic effects and underlying mechanisms of THCQT on vascular endothelial injury induced by HBSS.Methods:LC-MS/MS was used to analyze the chemical components of THCQT.The intervention involved administering saline and appropriate drugs to rats via gavage for 21 days,followed by 24-h repeated tail vein injections of LPS to replicate the HBSS model.Pharmacodynamic assessments included measuring rat body temperature,hemorheology,coagulation function,fever mediators,inflammatory factors,vascular endothelial injury factors,and aortic histopathology to evaluate the preventive effect of THCQT on vascular endothelial injury caused by HBSS.Additionally,proteomics and transcriptomics analyses elucidated THCQT’s impact on mRNA and protein expression levels,further validated by quantitative real-time PCR and Western blot analysis.Results:THCQT was detected to contain 293 chemical components,and some active ingredients with high levels have anti-inflammatory,antioxidant,and inhibiting platelet aggregation properties.Pharmacodynamic results demonstrated that H-THCQT significantly suppressed the elevation of body temperature and downregulated TNF-α,cAMP,and PGE2 expression levels.Additionally,it attenuated the increase in WBV and PV,and prolonged APTT,PT,and TT.It enhanced the expression of NO and PGI2 in plasma,inhibiting ET-1 and TXA2 expression,thus ameliorating aortic pathological injury.Combined transcriptomics and proteomics analyses of the KEGG pathway suggest that the MAPK pathway is crucial in mitigating vascular endothelial injury induced by HBSS through THCQT administration.Furthermore,quantitative real-time PCR and Western blot analyses of the aorta indicated that THCQT inhibits the mRNA and protein phosphorylation levels of p38MAPK,ERK,and JNK in the MAPK signaling pathway of HBSS rats.Conclusion:Our work not only helps explore the common mechanism of THCQT in treating multi-system diseases induced by vascular endothelial injury due to HBSS but also provides a valuable research method for investigating the mechanisms underlying traditional Chinese medicine syndromes.展开更多
Objective:To systematically evaluate the efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis,and to provide evidence-based reference for clinical medication.Methods:The...Objective:To systematically evaluate the efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis,and to provide evidence-based reference for clinical medication.Methods:The randomized controlled trials of Xuebijing injection combined with conventional treatment(experimental group)versus conventional treatment(control group)for sepsis were collected by computer search of Chinese CNKI database,WANFANG database,and VIP database.Literature screening was performed according to the inclusion and exclusion criteria.According to the Cochrane International Collaboration Evaluator Workbook procedure,the quality evaluation and bias analysis were performed for the literatures included in the meta-analysis.Revman 5.3 software was used for systematic meta-analysis.Results:A total of 15 clinical randomized controlled trials with a total of 930 patients were included.Meta-analysis showed that Xuebijing injection combined with conventional therapy could reduce 28-day mortality in sepsis[OR=0.52,95%CI(0.38,0.71),P<0.0001],APACHEⅡintegral[WMD=-2.65,95%CI(-3.23,-2.08),P<0.00001];be effective in decreasing D-dimer[WMD=-0.79,95%CI(-1.17,-0.40),P<0.0001],TNF-α[WMD=-36.71,95%CI(-43.04,-30.39),P<0.00001],vWF[WMD=-15.94,95%CI(-27.60,-4.28),P=0.007],sE-selectin[WMD=-118.30,95%CI(-139.65,-96.95),P<0.00001],ESM-1[WMD=-135.44,95%CI(-186.30,-84.57),P<0.00001],sTM[WMD=-56.46,95%CI(-66.39,-46.53),P<0.00001];can effectively increase platelets[WMD=30.78,95%CI(25.65,35.92),P<0.00001].Conclusion:Xuebijing injection can not only effectively reduce the release of inflammatory factors,thereby improving vascular endothelial injury,reducing coagulation disorders and blocking coagulation-inflammation network;it can also increase the level of platelets,thereby repairing injured vascular endothelial cells,which has a certain value to reduce the condition of sepsis and improve the prognosis.It also provides some basis for the treatment of sepsis secondary to novel coronavirus pneumonia.展开更多
Objective:To investigate the therapeutic potential of octaarginine(R8)-modified essential oil from Fructus Alpiniae zerumbet(EOFAZ)lipid microspheres(EOFAZ@^(R8)LM)for cardiovascular therapy.Methods:EOFAZ@^(R8)LM was ...Objective:To investigate the therapeutic potential of octaarginine(R8)-modified essential oil from Fructus Alpiniae zerumbet(EOFAZ)lipid microspheres(EOFAZ@^(R8)LM)for cardiovascular therapy.Methods:EOFAZ@^(R8)LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM,followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury.The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential(MMP),intracellular reactive oxygen species(ROS)levels,as well as inflammatory factors interleukin-6(IL-6)and interleukin-1β(IL-1β)levels.Results:EOFAZ@^(R8)LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells,thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels.Moreover,it attenuated the expression levels of IL-6 and IL-1β,exerting protective effects on the vascular endothelium.Conclusion:Our findings highlight the significant therapeutic potential of EOFAZ@^(R8)LM in cardiovascular therapy,providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.展开更多
Objective To observe the prevention of Fangshuan Capsule(FC)on percutaneous coronary intervention(PCI)induced myocardial damage and vascular endothelial injury in patients with unstable angina pectoris(UAP).Methods To...Objective To observe the prevention of Fangshuan Capsule(FC)on percutaneous coronary intervention(PCI)induced myocardial damage and vascular endothelial injury in patients with unstable angina pectoris(UAP).Methods Totally 100 UAP patients undergoing PCI were assigned to the control group and the展开更多
BACKGROUND： Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor （VEGF） on in...BACKGROUND： Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor （VEGF） on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic. OBJECTIVE： To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia /reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia. DESIGN： A randomized controlled animal tria SETTNG： Department of Medical Imaging, Second Hospital of Hebei Medical University MATERIALS： Sixty-five healthy male New Zealand rabbits of clean degree, weighing （2.6±0.2） kg, aged 4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia （Beijing Zhongshan Company）, recombinant VEGF165 （Peprotech Company, USA）, biotinylated second antibody and ABC compound （Wuhan Boster Company） were applied. METHODS： The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy, Second Hospital of Hebei Medical University from May to August in 2005. （1） The rabbits were randomly divided into three groups： sham-operated group （n=15）, control group （n=25） and VEGF-treated group （n=-25）. In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion （MCAO） induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165 （2.5 mg/L） was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabbits in the sham-operated group were only drilled but not administrated. （2） The experimental indexes were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The brain tissues in the surrounding regions of the infarcted sites were collected. The positive expressions of the factors of vascular pseudohemophilia in vascular endothelial cells were analyzed with immunohistochemical method. The microvessels in unit statistical field were counted with the imaging analytical software. MAIN OUTCOME MEASURES： The changes of microvascular density in the brain tissue and the positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of the infarcted sites were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment. RESULTS： All the 65 New Zealand rabbits were involved in the analysis of results without deletion. Changes of the number of microvessels at different time points in each group： There were no obvious changes at different time points in the sham-operated group. The numbers of microvessels at 7 and 14 days were obviously more in the control group than in the sham-operated group [（6.0±1.1）, （9.0±0.9） microvessels; （3.0±1.1）, （3.0±1.1） microvessels; P〈 0.05-0.01], and those at 3, 7, 14 and 28 days were obviously more in the VEGF-treated group than in the control group [（8.3±2.0）, （13.4±1.4）, （15.5±2.3）, （6.8± 1.0） microvessels; （3.4±0.6）, （6.0±1.1）, （9.0±0.9）, （3.2±0.8） microvessels; P 〈 0.01]. （2） Positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of infarcted sites： There were no obvious changes at different time points in the sham-operated group. In the control group, the changing law of the expressions was the same as that for the number of microvessels that the expression began to mildly increase at 7 days, reached the peak value at 14 days, and began to reduce at 28 days. In the VEGF-treated group, the expression was obviously increased at 3 days, also reached the peak value at 14 days, and reduced to the normal level at 70 days, but the expressions were obviously stronger than those in the control group at the same time points. CONCLUSION： Angiogenesis can be obviously induced in rabbits after the focal cerebral ischemia/reperfusion injury is treated with VEGF for 18 days.展开更多
Background It＇s established that Lectin-like involved in intimal hyperplasia after balloon injury oxidized low-density lipoprotein receptor-l（LOX-1） is The recent evidence also suggests that valsartan has an antia...Background It＇s established that Lectin-like involved in intimal hyperplasia after balloon injury oxidized low-density lipoprotein receptor-l（LOX-1） is The recent evidence also suggests that valsartan has an antiatheroscletic effect. In this study, the expression of LOX-1 and the effect of valsartan on its expression was investigated in rat aorta after balloon injury. Methods Rat model of aortic endothelial denudation was induced by 2F balloon catheter. Rats were randomly divided into three groups： control, operationand valsartan treatment. The aortic tissues were taken from rats in each group on days 14 and 28 after surgery. The thickness of vascular wall was measured with HE stain, LOX-1 mRNA and protein were determined by reverse transcription-polymerse chain reaction （RT-PCR） and immunohistochemistry, respectively. Results Compared with the control group, significant intimal thickening was observed at day 14 and 28 after injury. Compared with the operation group, intimal thickness of each time point was significantly decreased in valsartan treatment group. At day 14 and 28 after balloon injury, the expression levels of LOX-1 mRNA and protein were significantly increased, and were greatly decreased after valsartan treatment. Conclusions The expression of LOX-1 is increased after endothelial injury. Valsartan inhibits aortic intimal thickening induced by endothelial denudation, which is associated with the downregulation of LOX-1 expression.展开更多
基金supported by the National Natural Science Foundation of China(grant No.81973592)the Shaanxi Provincial Administration of Traditional Chinese Medicine Project(grant No.2021-GJ-JC004).
文摘Background:Heat and Blood Stasis Syndrome(HBSS),a syndrome in traditional Chinese medicine is intrinsically linked to vascular endothelial injury.Taohe Chengqi Decoction(THCQT)is considered to treat diseases related to HBSS by improving inflammatory response,oxidative stress,and blood circulation disorder.This study aimed to elucidate the therapeutic effects and underlying mechanisms of THCQT on vascular endothelial injury induced by HBSS.Methods:LC-MS/MS was used to analyze the chemical components of THCQT.The intervention involved administering saline and appropriate drugs to rats via gavage for 21 days,followed by 24-h repeated tail vein injections of LPS to replicate the HBSS model.Pharmacodynamic assessments included measuring rat body temperature,hemorheology,coagulation function,fever mediators,inflammatory factors,vascular endothelial injury factors,and aortic histopathology to evaluate the preventive effect of THCQT on vascular endothelial injury caused by HBSS.Additionally,proteomics and transcriptomics analyses elucidated THCQT’s impact on mRNA and protein expression levels,further validated by quantitative real-time PCR and Western blot analysis.Results:THCQT was detected to contain 293 chemical components,and some active ingredients with high levels have anti-inflammatory,antioxidant,and inhibiting platelet aggregation properties.Pharmacodynamic results demonstrated that H-THCQT significantly suppressed the elevation of body temperature and downregulated TNF-α,cAMP,and PGE2 expression levels.Additionally,it attenuated the increase in WBV and PV,and prolonged APTT,PT,and TT.It enhanced the expression of NO and PGI2 in plasma,inhibiting ET-1 and TXA2 expression,thus ameliorating aortic pathological injury.Combined transcriptomics and proteomics analyses of the KEGG pathway suggest that the MAPK pathway is crucial in mitigating vascular endothelial injury induced by HBSS through THCQT administration.Furthermore,quantitative real-time PCR and Western blot analyses of the aorta indicated that THCQT inhibits the mRNA and protein phosphorylation levels of p38MAPK,ERK,and JNK in the MAPK signaling pathway of HBSS rats.Conclusion:Our work not only helps explore the common mechanism of THCQT in treating multi-system diseases induced by vascular endothelial injury due to HBSS but also provides a valuable research method for investigating the mechanisms underlying traditional Chinese medicine syndromes.
基金Shaanxi Provincial Administration of Traditional Chinese Medicine 2020 Special Project of Pneumonia Scientific Research on Prevention and Treatment of Novel Coronavirus with Traditional Chinese Medicine(No.SZY-KJCYC-2020-YJ001)Shaanxi Provincial Department of Science and Technology Key Research and Development Project(No.2017ZDXM-SF-109)Shaanxi Provincial Infectious Diseases Clinical Medicine Research Center(Integrated Traditional Chinese and Western Medicine)Project(No.2020LCZX-02)。
文摘Objective:To systematically evaluate the efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis,and to provide evidence-based reference for clinical medication.Methods:The randomized controlled trials of Xuebijing injection combined with conventional treatment(experimental group)versus conventional treatment(control group)for sepsis were collected by computer search of Chinese CNKI database,WANFANG database,and VIP database.Literature screening was performed according to the inclusion and exclusion criteria.According to the Cochrane International Collaboration Evaluator Workbook procedure,the quality evaluation and bias analysis were performed for the literatures included in the meta-analysis.Revman 5.3 software was used for systematic meta-analysis.Results:A total of 15 clinical randomized controlled trials with a total of 930 patients were included.Meta-analysis showed that Xuebijing injection combined with conventional therapy could reduce 28-day mortality in sepsis[OR=0.52,95%CI(0.38,0.71),P<0.0001],APACHEⅡintegral[WMD=-2.65,95%CI(-3.23,-2.08),P<0.00001];be effective in decreasing D-dimer[WMD=-0.79,95%CI(-1.17,-0.40),P<0.0001],TNF-α[WMD=-36.71,95%CI(-43.04,-30.39),P<0.00001],vWF[WMD=-15.94,95%CI(-27.60,-4.28),P=0.007],sE-selectin[WMD=-118.30,95%CI(-139.65,-96.95),P<0.00001],ESM-1[WMD=-135.44,95%CI(-186.30,-84.57),P<0.00001],sTM[WMD=-56.46,95%CI(-66.39,-46.53),P<0.00001];can effectively increase platelets[WMD=30.78,95%CI(25.65,35.92),P<0.00001].Conclusion:Xuebijing injection can not only effectively reduce the release of inflammatory factors,thereby improving vascular endothelial injury,reducing coagulation disorders and blocking coagulation-inflammation network;it can also increase the level of platelets,thereby repairing injured vascular endothelial cells,which has a certain value to reduce the condition of sepsis and improve the prognosis.It also provides some basis for the treatment of sepsis secondary to novel coronavirus pneumonia.
基金supported by the National Natural Science Foundation of China(Nos.82260827 and U1812403-4-4)the Guizhou Provincial Science Technology Project(No.ZK[2022]380)+3 种基金the Guizhou Provincial Natural Science Foundation(Nos.[2020]1Z069 and[2020]1Y210)the Guizhou Provincial Scientific and Technologic Innovation Base(No.[2023]003)the Cultivation Project of National Natural Science Foundation of Guizhou Medical University(Nos.21NSFCP47 and 20NSP053)the High level Innovation Talents(No.GCC[2023]048)。
文摘Objective:To investigate the therapeutic potential of octaarginine(R8)-modified essential oil from Fructus Alpiniae zerumbet(EOFAZ)lipid microspheres(EOFAZ@^(R8)LM)for cardiovascular therapy.Methods:EOFAZ@^(R8)LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM,followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury.The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential(MMP),intracellular reactive oxygen species(ROS)levels,as well as inflammatory factors interleukin-6(IL-6)and interleukin-1β(IL-1β)levels.Results:EOFAZ@^(R8)LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells,thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels.Moreover,it attenuated the expression levels of IL-6 and IL-1β,exerting protective effects on the vascular endothelium.Conclusion:Our findings highlight the significant therapeutic potential of EOFAZ@^(R8)LM in cardiovascular therapy,providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.
文摘Objective To observe the prevention of Fangshuan Capsule(FC)on percutaneous coronary intervention(PCI)induced myocardial damage and vascular endothelial injury in patients with unstable angina pectoris(UAP).Methods Totally 100 UAP patients undergoing PCI were assigned to the control group and the
文摘BACKGROUND： Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor （VEGF） on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic. OBJECTIVE： To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia /reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia. DESIGN： A randomized controlled animal tria SETTNG： Department of Medical Imaging, Second Hospital of Hebei Medical University MATERIALS： Sixty-five healthy male New Zealand rabbits of clean degree, weighing （2.6±0.2） kg, aged 4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia （Beijing Zhongshan Company）, recombinant VEGF165 （Peprotech Company, USA）, biotinylated second antibody and ABC compound （Wuhan Boster Company） were applied. METHODS： The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy, Second Hospital of Hebei Medical University from May to August in 2005. （1） The rabbits were randomly divided into three groups： sham-operated group （n=15）, control group （n=25） and VEGF-treated group （n=-25）. In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion （MCAO） induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165 （2.5 mg/L） was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabbits in the sham-operated group were only drilled but not administrated. （2） The experimental indexes were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The brain tissues in the surrounding regions of the infarcted sites were collected. The positive expressions of the factors of vascular pseudohemophilia in vascular endothelial cells were analyzed with immunohistochemical method. The microvessels in unit statistical field were counted with the imaging analytical software. MAIN OUTCOME MEASURES： The changes of microvascular density in the brain tissue and the positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of the infarcted sites were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment. RESULTS： All the 65 New Zealand rabbits were involved in the analysis of results without deletion. Changes of the number of microvessels at different time points in each group： There were no obvious changes at different time points in the sham-operated group. The numbers of microvessels at 7 and 14 days were obviously more in the control group than in the sham-operated group [（6.0±1.1）, （9.0±0.9） microvessels; （3.0±1.1）, （3.0±1.1） microvessels; P〈 0.05-0.01], and those at 3, 7, 14 and 28 days were obviously more in the VEGF-treated group than in the control group [（8.3±2.0）, （13.4±1.4）, （15.5±2.3）, （6.8± 1.0） microvessels; （3.4±0.6）, （6.0±1.1）, （9.0±0.9）, （3.2±0.8） microvessels; P 〈 0.01]. （2） Positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of infarcted sites： There were no obvious changes at different time points in the sham-operated group. In the control group, the changing law of the expressions was the same as that for the number of microvessels that the expression began to mildly increase at 7 days, reached the peak value at 14 days, and began to reduce at 28 days. In the VEGF-treated group, the expression was obviously increased at 3 days, also reached the peak value at 14 days, and reduced to the normal level at 70 days, but the expressions were obviously stronger than those in the control group at the same time points. CONCLUSION： Angiogenesis can be obviously induced in rabbits after the focal cerebral ischemia/reperfusion injury is treated with VEGF for 18 days.
基金supported by Science and Technology sponsor project of Shandong Province(No.2012G0021851)
文摘Background It＇s established that Lectin-like involved in intimal hyperplasia after balloon injury oxidized low-density lipoprotein receptor-l（LOX-1） is The recent evidence also suggests that valsartan has an antiatheroscletic effect. In this study, the expression of LOX-1 and the effect of valsartan on its expression was investigated in rat aorta after balloon injury. Methods Rat model of aortic endothelial denudation was induced by 2F balloon catheter. Rats were randomly divided into three groups： control, operationand valsartan treatment. The aortic tissues were taken from rats in each group on days 14 and 28 after surgery. The thickness of vascular wall was measured with HE stain, LOX-1 mRNA and protein were determined by reverse transcription-polymerse chain reaction （RT-PCR） and immunohistochemistry, respectively. Results Compared with the control group, significant intimal thickening was observed at day 14 and 28 after injury. Compared with the operation group, intimal thickness of each time point was significantly decreased in valsartan treatment group. At day 14 and 28 after balloon injury, the expression levels of LOX-1 mRNA and protein were significantly increased, and were greatly decreased after valsartan treatment. Conclusions The expression of LOX-1 is increased after endothelial injury. Valsartan inhibits aortic intimal thickening induced by endothelial denudation, which is associated with the downregulation of LOX-1 expression.
