Wang Chunmei, Li Jing, Lv Xiaoyan, Zhang Ming, Song Yanfang, Chen Li, Liu Yanjun
Department of Pharmacology, Bethune Medical College of Jilin University, Changchun, PR China.
Eur J Pharmacol. 2009 Oct 12;620(1-3):131-7. doi: 10.1016/j.ejphar.2009.07.027. Epub 2009 Aug 15.
Berberine can improve insulin resistance, lower blood glucose, and regulate lipid metabolism disorders which cause endothelial dysfunction, leading to vascular complications of type 2 diabetes mellitus. The aim of the present study was to investigate the effects of berberine on endothelial dysfunction of aortas in type 2 diabetes mellitus rats and its mechanism. Wistar rats were randomly divided into four groups: diabetic rats, control rats, diabetic rats treated with berberine (100 mg/kg), and control rats treated with berberine. The serum fasting blood glucose, insulin, total cholesterol, triglyceride and nitric oxide (NO) levels were tested. Acetylcholine-induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. The expression of endothelial nitric oxide synthase (eNOS) mRNA was measured by RT-PCR, and the protein expressions of eNOS and NADPH oxidase (NOX4) were analyzed by western blot. The results showed that berberine significantly decreased fasting blood glucose, and triglyceride levels in diabetic rats. Berberine also improved endothelium-dependent vasorelaxation impaired in aorta. The expressions of eNOS mRNA and protein were significantly increased, while NOX4 protein expression was decreased in aortas from diabetic rats with berberine treatment. Moreover, serum NO levels were elevated after berberine treatment. In conclusion, berberine restores diabetic endothelial dysfunction through enhanced NO bioavailability by up-regulating eNOS expression and down-regulating expression of NADPH oxidase.
黄连素可改善胰岛素抵抗、降低血糖,并调节导致内皮功能障碍的脂质代谢紊乱,进而引发2型糖尿病的血管并发症。本研究旨在探讨黄连素对2型糖尿病大鼠主动脉内皮功能障碍的影响及其机制。将Wistar大鼠随机分为四组:糖尿病大鼠、对照大鼠、用黄连素治疗的糖尿病大鼠(100 mg/kg)和用黄连素治疗的对照大鼠。检测血清空腹血糖、胰岛素、总胆固醇、甘油三酯和一氧化氮(NO)水平。在主动脉中测量乙酰胆碱诱导的内皮依赖性舒张和硝普钠诱导的非内皮依赖性舒张,以评估内皮功能。通过RT-PCR检测内皮型一氧化氮合酶(eNOS)mRNA的表达,通过蛋白质印迹分析eNOS和NADPH氧化酶(NOX4)的蛋白质表达。结果表明,黄连素显著降低糖尿病大鼠的空腹血糖和甘油三酯水平。黄连素还改善了主动脉中受损的内皮依赖性血管舒张。在用黄连素治疗的糖尿病大鼠的主动脉中,eNOS mRNA和蛋白质的表达显著增加,而NOX4蛋白质表达降低。此外,黄连素治疗后血清NO水平升高。综上所述,黄连素通过上调eNOS表达和下调NADPH氧化酶表达来增强NO生物利用度,从而恢复糖尿病性内皮功能障碍。