AIM:To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices.METHODS:Experimental rats were fed a modified Lieber-De Carli alcohol(6%) and high-fat(65%...AIM:To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices.METHODS:Experimental rats were fed a modified Lieber-De Carli alcohol(6%) and high-fat(65%) diet(AHF) for 10 wk while control animals received a regular rodent chow diet.Weekly behavioral tests determinedmechanical and heat sensitivity.In week 10 a fasting glucose tolerance test was performed,measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal(i.p.) injection of glucose.Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin.Pancreas sections were also stained with Sirius red and fast green to quantify collagen content.Insulinexpressing cells were identified immunohistochemically in separate sections.Tissue staining density was quantified using Image J software.After mechanical and heat sensitivity became stable(weeks 6-10) in the AHF-fed animals,three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity:a Group Ⅱ metabotropic glutamate receptor specific agonist(2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate(APDC,3 mg/kg,ip; Tocris,Bristol,United Kingdom),nociceptin(20,60,200 nmol/kg,ip; Tocris),and morphine sulfate(3 mg/kg,μ-opioid receptor agonist; Baxter Healthcare,Deerfield,IL,United States).RESULTS:Histological analysis of pancreas and liver determined that unlike control rats,AHF fed animals had pancreatic fibrosis,acinar and beta cell atrophy,with steatosis in both organs.Fat vacuolization was significantly increased in AHF fed rats(6.4% ± 1.1% in controls vs 23.8% ± 4.2%,P < 0.05).Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls(127.4 ± 9.2 mg/d L in controls vs 161.0 ± 8.6 mg/d L,P < 0.05).This concurred with a 3.5 fold higher incidence of single and small 2-10 cell insulin-positive cell clusters(P < 0.05).Insulin expressing islet of Langerhans cells appeared hypertrophied while islet number and area measurements were not different from controls.Weekly behavioral tests determined that mechanical and heat sensitivities were significantly increased by 4 wk on AHF diet compared to controls.Hypersensitivitywas attenuated with efficacy similar to morphine with single dose treatment of either metabotropic glutamate receptor 2/3 agonist APDC,or nociceptin,the endogenous ligand for opioid-receptor-like 1 receptor.CONCLUSION:The AHF diet induces a chronic alcoholic pancreatitis in rats with measurable features resembling clinical patients with chronic pancreatitis and type 3c diabetes mellitus.展开更多
Hypoxia is closely related to many diseases and often leads to death.Early detection andidentification of the hypoxia causes may help to promptly determine the right rescue plan andreduce the mortality.We proposed a n...Hypoxia is closely related to many diseases and often leads to death.Early detection andidentification of the hypoxia causes may help to promptly determine the right rescue plan andreduce the mortality.We proposed a new multiparametric monitoring method employingmitochondrial reduced nicotinamide adenine dinucleotide(NA DH)fluorescence,regional reflectance,regional cerebral blood flow(CBF),electrocardiography(ECG),and respiration under sixkinds of acute hypoxia in four categories to investigate a correlation bet ween the parametervariances and the hypoxia causes.The variation patterns of the paramet ers were discussed,andthe combination of NADH and CBF may contribute to the identification of the causes of hypoxia.展开更多
基金Supported by National Institutes of Health,No.NINDS R01 NS39041
文摘AIM:To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices.METHODS:Experimental rats were fed a modified Lieber-De Carli alcohol(6%) and high-fat(65%) diet(AHF) for 10 wk while control animals received a regular rodent chow diet.Weekly behavioral tests determinedmechanical and heat sensitivity.In week 10 a fasting glucose tolerance test was performed,measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal(i.p.) injection of glucose.Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin.Pancreas sections were also stained with Sirius red and fast green to quantify collagen content.Insulinexpressing cells were identified immunohistochemically in separate sections.Tissue staining density was quantified using Image J software.After mechanical and heat sensitivity became stable(weeks 6-10) in the AHF-fed animals,three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity:a Group Ⅱ metabotropic glutamate receptor specific agonist(2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate(APDC,3 mg/kg,ip; Tocris,Bristol,United Kingdom),nociceptin(20,60,200 nmol/kg,ip; Tocris),and morphine sulfate(3 mg/kg,μ-opioid receptor agonist; Baxter Healthcare,Deerfield,IL,United States).RESULTS:Histological analysis of pancreas and liver determined that unlike control rats,AHF fed animals had pancreatic fibrosis,acinar and beta cell atrophy,with steatosis in both organs.Fat vacuolization was significantly increased in AHF fed rats(6.4% ± 1.1% in controls vs 23.8% ± 4.2%,P < 0.05).Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls(127.4 ± 9.2 mg/d L in controls vs 161.0 ± 8.6 mg/d L,P < 0.05).This concurred with a 3.5 fold higher incidence of single and small 2-10 cell insulin-positive cell clusters(P < 0.05).Insulin expressing islet of Langerhans cells appeared hypertrophied while islet number and area measurements were not different from controls.Weekly behavioral tests determined that mechanical and heat sensitivities were significantly increased by 4 wk on AHF diet compared to controls.Hypersensitivitywas attenuated with efficacy similar to morphine with single dose treatment of either metabotropic glutamate receptor 2/3 agonist APDC,or nociceptin,the endogenous ligand for opioid-receptor-like 1 receptor.CONCLUSION:The AHF diet induces a chronic alcoholic pancreatitis in rats with measurable features resembling clinical patients with chronic pancreatitis and type 3c diabetes mellitus.
基金supported bythe 111 Project of China(B07038)alsosupported by the Ph.D.Programs Foundation of the Mimnistry of Education of China(Grant_No.20110142130006)the Director Fund of Wuhan National Laboratory for Optoelectronics(WNLO,2009,Z.H.ZHANG).
文摘Hypoxia is closely related to many diseases and often leads to death.Early detection andidentification of the hypoxia causes may help to promptly determine the right rescue plan andreduce the mortality.We proposed a new multiparametric monitoring method employingmitochondrial reduced nicotinamide adenine dinucleotide(NA DH)fluorescence,regional reflectance,regional cerebral blood flow(CBF),electrocardiography(ECG),and respiration under sixkinds of acute hypoxia in four categories to investigate a correlation bet ween the parametervariances and the hypoxia causes.The variation patterns of the paramet ers were discussed,andthe combination of NADH and CBF may contribute to the identification of the causes of hypoxia.
