目的探讨槲皮素对高糖培养海马神经元凋亡影响的可能作用机制。方法新生24 h Sprague-Dawley大鼠,取海马神经元原代培养,分为正常对照组、高糖组、槲皮素组、槲皮素+Akt抑制剂组和Akt激动剂组。各组在不同条件培养基中培养72 h后流式细...目的探讨槲皮素对高糖培养海马神经元凋亡影响的可能作用机制。方法新生24 h Sprague-Dawley大鼠,取海马神经元原代培养,分为正常对照组、高糖组、槲皮素组、槲皮素+Akt抑制剂组和Akt激动剂组。各组在不同条件培养基中培养72 h后流式细胞仪检测细胞凋亡率,Western blotting检测各组神经元p-Akt、Akt、Bcl-2和Bax蛋白表达。结果与正常对照组相比,高糖组细胞凋亡率明显升高(P<0.01),p-Akt/Akt和Bcl-2/Bax均明显减少(P<0.01);与高糖组比较,槲皮素组、Akt激动剂组细胞凋亡率明显下降(P<0.01),p-Akt/Akt和Bcl-2/Bax均明显升高(P<0.01)。与槲皮素+Akt抑制剂组比较,槲皮素组细胞凋亡率明显下降(P<0.01),p-Akt/Akt和Bcl-2/Bax均明显升高(P<0.01)。结论槲皮素能够减少高糖培养下海马神经元的凋亡,其作用机制与增加Akt信号通路中Akt蛋白磷酸化的程度,进而增加Bcl-2蛋白的表达、抑制Bax蛋白的表达有关。展开更多
Objective:To assess the efficacy and safety of mulberry twig alkaloids(Sangzhi alkaloids,SZ-A)for treatment of type 2 diabetes in a randomized,double-blind,placebo-controlled multicenter clinical trial.Methods:A total...Objective:To assess the efficacy and safety of mulberry twig alkaloids(Sangzhi alkaloids,SZ-A)for treatment of type 2 diabetes in a randomized,double-blind,placebo-controlled multicenter clinical trial.Methods:A total of 200 patients were randomized to receive SZ-A(n=100)or placebo(n=100)for 16 weeks.The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs.The primary outcome was the change in glycosylated hemoglobin(Hb A1c)level.The secondary outcome included the proportions of cases with Hb A1c<7.0%and Hb A1c<6.5%,fasting blood glucose(FBG),postprandial blood glucose(PBG),area under curve for the PBG(AUC_(0-2h)),body weight,and body mass index(BMI).Adverse events(AEs),severe adverse events(SAEs),treatment-related adverse events(TAEs),gastrointestinal disorders(GDs),blood pressure,routine blood tests,and liver and kidney function were monitored.Results:Compared with baseline,the change of Hb A1c at week 16 was-0.80%(95%CI:-0.98%to-0.62%)and-0.09%(95%CI:-0.27%to 0.09%)in SZ-A group and placebo group,respectively.The proportion of patients with Hb A1c<7%and<6.5%was higher in the SZ-A group than in the placebo group(46.8%vs.21.6%and 29.9%vs.10.8%).The observed values and changes in FBG,1 h-PBG,2 h-PBG,and AUC_(0-2h) differed significantly between groups(P<0.001),but differences were not significant in body weight and BMI(P>0.05).The incidence rates of AEs,TAEs,and GDs differed significantly between groups(P=0.010,P=0.005,and P=0.006,respectively),whereas the incidence rates of SAEs showed no significant differences between groups(P=1.000).Conclusion:SZ-A are effective and safe for treatment of type 2 diabetes.展开更多
文摘目的探讨槲皮素对高糖培养海马神经元凋亡影响的可能作用机制。方法新生24 h Sprague-Dawley大鼠,取海马神经元原代培养,分为正常对照组、高糖组、槲皮素组、槲皮素+Akt抑制剂组和Akt激动剂组。各组在不同条件培养基中培养72 h后流式细胞仪检测细胞凋亡率,Western blotting检测各组神经元p-Akt、Akt、Bcl-2和Bax蛋白表达。结果与正常对照组相比,高糖组细胞凋亡率明显升高(P<0.01),p-Akt/Akt和Bcl-2/Bax均明显减少(P<0.01);与高糖组比较,槲皮素组、Akt激动剂组细胞凋亡率明显下降(P<0.01),p-Akt/Akt和Bcl-2/Bax均明显升高(P<0.01)。与槲皮素+Akt抑制剂组比较,槲皮素组细胞凋亡率明显下降(P<0.01),p-Akt/Akt和Bcl-2/Bax均明显升高(P<0.01)。结论槲皮素能够减少高糖培养下海马神经元的凋亡,其作用机制与增加Akt信号通路中Akt蛋白磷酸化的程度,进而增加Bcl-2蛋白的表达、抑制Bax蛋白的表达有关。
基金Supported by the National Major Science and Technology Projects of China(No.2013ZX09101005)。
文摘Objective:To assess the efficacy and safety of mulberry twig alkaloids(Sangzhi alkaloids,SZ-A)for treatment of type 2 diabetes in a randomized,double-blind,placebo-controlled multicenter clinical trial.Methods:A total of 200 patients were randomized to receive SZ-A(n=100)or placebo(n=100)for 16 weeks.The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs.The primary outcome was the change in glycosylated hemoglobin(Hb A1c)level.The secondary outcome included the proportions of cases with Hb A1c<7.0%and Hb A1c<6.5%,fasting blood glucose(FBG),postprandial blood glucose(PBG),area under curve for the PBG(AUC_(0-2h)),body weight,and body mass index(BMI).Adverse events(AEs),severe adverse events(SAEs),treatment-related adverse events(TAEs),gastrointestinal disorders(GDs),blood pressure,routine blood tests,and liver and kidney function were monitored.Results:Compared with baseline,the change of Hb A1c at week 16 was-0.80%(95%CI:-0.98%to-0.62%)and-0.09%(95%CI:-0.27%to 0.09%)in SZ-A group and placebo group,respectively.The proportion of patients with Hb A1c<7%and<6.5%was higher in the SZ-A group than in the placebo group(46.8%vs.21.6%and 29.9%vs.10.8%).The observed values and changes in FBG,1 h-PBG,2 h-PBG,and AUC_(0-2h) differed significantly between groups(P<0.001),but differences were not significant in body weight and BMI(P>0.05).The incidence rates of AEs,TAEs,and GDs differed significantly between groups(P=0.010,P=0.005,and P=0.006,respectively),whereas the incidence rates of SAEs showed no significant differences between groups(P=1.000).Conclusion:SZ-A are effective and safe for treatment of type 2 diabetes.
