目的:观察左归复方干预治疗对骨骼肌胰岛素样生长因子-1及胰岛素双受体功能缺失(Mouse overexpressing a dominant-negative IGF-I receptor specifically in muscle,MKR mouse)转基因2型糖尿病小鼠的糖代谢及相关炎症因子细胞间黏附分...目的:观察左归复方干预治疗对骨骼肌胰岛素样生长因子-1及胰岛素双受体功能缺失(Mouse overexpressing a dominant-negative IGF-I receptor specifically in muscle,MKR mouse)转基因2型糖尿病小鼠的糖代谢及相关炎症因子细胞间黏附分子、血管细胞黏附分子的影响。方法:由美国国立卫生研究院(NIH)授权使用引进的MKR鼠,经自然交配后繁殖的子代作为研究对象。MKR小鼠经繁殖鉴定后,以左归复方给药30d进行干预治疗。结果:MKR鼠后代能稳定遗传。左归复方给药30天后,其高剂量具有显著的改善MKR鼠糖耐量异常、降低空腹血糖和改善高胰岛素血症的作用(P<0.05,P<0.01),并具有降低细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子(VCAM-1)水平的作用(P<0.01)。结论:我们成功地引进了MKR模型,MKR鼠是目前一种非常良好的2型糖尿病的动物模型。左归复方具有显著的改善MKR鼠糖代谢的作用,并具有降低与炎症反应相关的细胞间黏附分子和血管细胞黏附分子水平的作用。展开更多
Objective:To investigate apoptotic effects of berberine,a significant alkaloids component existing in Rhizoma coptidis,and its possible acting mechanism in insulinoma cells.Methods:Different concentrations of berberin...Objective:To investigate apoptotic effects of berberine,a significant alkaloids component existing in Rhizoma coptidis,and its possible acting mechanism in insulinoma cells.Methods:Different concentrations of berberine were used to treat mouse insulinoma(MIN6)cells for various period of time.The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay,flow cytometry and enzyme-linked immuno sorbent assay.Changes in the relating pro-and anti-apoptosis proteins were detected by western-blotting.Results:The half-maximal inhibitory concentration(IC50)of berberine was 5.7μmol/L on MIN6 cells viability for 16 h.Berberine caused a 20%reduction(P<0.05)in cell number after only 4-h incubation;which reached 50%after 24 h(P<0.01).Berberine treatment for 16 h significantly increased the level of DNA fragmentation.The flow cytometry showed the apoptotic rate increased 2.9-and 4.6-fold after treating with berberine(5μmol/L)for 8 and 16 h,while 3-and 8.7-fold after 10μmol/L treatment for 8 and 16 h(P<0.01).Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2.Meanwhile,berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm.Apoptotic protease-activating factor 1(Apaf-1)was subsequently activated after cytochrome C release.Furthermore,caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade.Conclusion:High concentration(5 and 10μmol/L)of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor(AIF)pathway.展开更多
文摘目的:观察左归复方干预治疗对骨骼肌胰岛素样生长因子-1及胰岛素双受体功能缺失(Mouse overexpressing a dominant-negative IGF-I receptor specifically in muscle,MKR mouse)转基因2型糖尿病小鼠的糖代谢及相关炎症因子细胞间黏附分子、血管细胞黏附分子的影响。方法:由美国国立卫生研究院(NIH)授权使用引进的MKR鼠,经自然交配后繁殖的子代作为研究对象。MKR小鼠经繁殖鉴定后,以左归复方给药30d进行干预治疗。结果:MKR鼠后代能稳定遗传。左归复方给药30天后,其高剂量具有显著的改善MKR鼠糖耐量异常、降低空腹血糖和改善高胰岛素血症的作用(P<0.05,P<0.01),并具有降低细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子(VCAM-1)水平的作用(P<0.01)。结论:我们成功地引进了MKR模型,MKR鼠是目前一种非常良好的2型糖尿病的动物模型。左归复方具有显著的改善MKR鼠糖代谢的作用,并具有降低与炎症反应相关的细胞间黏附分子和血管细胞黏附分子水平的作用。
基金Supported by the National Natural Science Foundation of China(No.NSFC81274041 and No.NSFC81273995)the International Cooperation Projects of Ministry of Education(No.2011DFA30920)the Key Drug Development Program of Ministry of Science an Technology(No.20122X09103201-005)
文摘Objective:To investigate apoptotic effects of berberine,a significant alkaloids component existing in Rhizoma coptidis,and its possible acting mechanism in insulinoma cells.Methods:Different concentrations of berberine were used to treat mouse insulinoma(MIN6)cells for various period of time.The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay,flow cytometry and enzyme-linked immuno sorbent assay.Changes in the relating pro-and anti-apoptosis proteins were detected by western-blotting.Results:The half-maximal inhibitory concentration(IC50)of berberine was 5.7μmol/L on MIN6 cells viability for 16 h.Berberine caused a 20%reduction(P<0.05)in cell number after only 4-h incubation;which reached 50%after 24 h(P<0.01).Berberine treatment for 16 h significantly increased the level of DNA fragmentation.The flow cytometry showed the apoptotic rate increased 2.9-and 4.6-fold after treating with berberine(5μmol/L)for 8 and 16 h,while 3-and 8.7-fold after 10μmol/L treatment for 8 and 16 h(P<0.01).Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2.Meanwhile,berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm.Apoptotic protease-activating factor 1(Apaf-1)was subsequently activated after cytochrome C release.Furthermore,caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade.Conclusion:High concentration(5 and 10μmol/L)of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor(AIF)pathway.
