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目的研究小檗碱及8-羟基二氢小檗碱对2型糖尿病大鼠血管内皮功能的影响。方法采用高脂喂养并尾静脉注射小剂量链脲佐菌素的方法制备2型糖尿病动物模型,将2型糖尿病大鼠随机分为模型组、小檗碱组、8-羟基二氢小檗碱组(低、中、高剂量组),另设正常对照组。药物干预治疗前后对各组动物进行口服糖耐量实验(OGTT),干预治疗6周之后检测血清胰岛素(Ins)、血管活性因子(ET-1,NO,PGI2,TXA2)、von Willy Brand因子(vWF)、血管紧张素-2(AngⅡ)、凝血-纤溶系统因子(Fg,PAI-1)等水平。结果小檗碱组及8-羟基二氢小檗碱各剂量组OGTT,血脂较模型组均改善;INS、ET、AngⅡ、TXA2、vWF因子、Fg、PAI-1水平低于模型组(均P<0.01),而NO、PGI2水平高于模型组(均P<0.01)。与小檗碱组相比,8-羟基二氢小檗碱各剂量组治疗后OGTT、血脂、血管活性因子、vWF、AngⅡ及凝血-纤溶系统因子改善情况均优于小檗碱组。结论小檗碱及8-羟基二氢小檗碱能够降糖,降脂,改善胰岛素抵抗,调节血管内皮,对2型糖尿病早期出现的血管内皮损伤有良好的保护作用,且8-羟基二氢小檗碱比小檗碱更有优势。
Objective To study the effects of berberine and 8-hydroxy-2-dihydroberberine on vascular endothelial function in type 2 diabetic rats. Methods Animal model of type 2 diabetes mellitus was established by feeding high fat diet and injecting small dose of streptozotocin intravenously. The type 2 diabetic rats were randomly divided into model group, berberine group, 8-hydroxy-dihydroberberine Group (low, medium and high dose group), another set of normal control group. Oral glucose tolerance test (OGTT) was performed on each group before and after drug intervention. Serum insulin, vasoactive factors (ET-1, NO, PGI2, TXA2) and von Willy Brand factor (vWF ), Angiotensin-2 (AngⅡ), coagulation-fibrinolysis system factor (Fg, PAI-1) and other levels. Results The levels of OGTT and blood lipids in berberine group and 8-hydroxy-2-dihydroberberine groups were significantly improved compared with those in model group. The levels of INS, ET, AngⅡ, TXA2, vWF, Fg and PAI- <0.01), while the levels of NO and PGI2 were higher than those in model group (all P <0.01). Compared with the berberine group, the improvement of OGTT, blood lipids, vasoactive factors, vWF, AngⅡ and coagulation-fibrinolysis system in the 8-hydroxy-2-dihydroberberine groups were better than those in the berberine group. Conclusion Berberine and 8-hydroxy-dihydroberberine can hypoglycemic, lipid-lowering and insulin resistance, regulate the vascular endothelium, and have a good protective effect on early vascular endothelial injury in type 2 diabetes mellitus, and 8-hydroxy-dihydro Berberine is more advantageous than berberine.