盐酸小檗碱对2型糖尿病大鼠血清炎症因子及胰腺β细胞形态的影响

目的观察盐酸小檗碱对2型糖尿病大鼠血清炎症因子水平的干预,以及对血糖、血清胰岛素、胰岛素敏感指数（insulin sensitive index,ISI）及胰腺β细胞形态学的影响,探讨盐酸小檗碱对改善糖尿病大鼠胰岛素抵抗的作用机理。方法健康雄性SD大鼠60只随机分为正常对照组、模型对照组、盐酸小檗碱组和二甲双胍组,每组15只,后三组在高脂饲料喂养30 d后,予以链脲佐菌素（streptozotocin,STZ）40 mg/kg制备2型糖尿病大鼠模型。成模后,盐酸小檗碱组予以盐酸小檗碱180 mg/（kg·d）灌胃30 d,二甲双胍组予以二甲双胍180 mg/（kg·d）灌胃30 d,检测实验大鼠的血清炎症因子水平、血糖、空腹胰岛素（fasting insulin,FINS）及ISI,并在光学显微镜和电子显微镜下观察各组胰腺β细胞的病理改变。结果模型对照组大鼠较正常对照组大鼠空腹血糖及空腹胰岛素水平均明显增高（P〈0.05）,血清炎症因子C反应蛋白（C-reactive protein,CRP）、IL-6,TNF-α亦明显增高（P〈0.05）。而二甲双胍组和盐酸小檗碱组的各项指标均较模型对照组明显下降（P〈0．05），但两药物治疗组之间无显著性差异（P〉0．05）。光学显微镜下HE染色，免疫组化染色及电子显微镜下观察胰腺β细胞形态，显示用药组较模型对照组均有不同程度的改善。结论盐酸小檗碱可通过降低2型糖尿病大鼠血清炎症因子水平而起到降低血糖、改善胰岛素抵抗的作用。

Effect of Berberine on serum inflammatory mediators and patho-morphology of beta cells in rats with type 2 diabetes

Objective To observe the interventional effect of Berberine on the serum levels of CPR, IL-6, TNF-α, bloodsugar, insulin and insulin sensitivity index in rat models with type 2 diabetes mellitus and to explore the mechanism of it＇ s function of improving rat insulin resistance. Methods Type 2 diabetes mellitus rat model was induced by intravenous injection of a low dose of streptozotocin （40 mg/kg） and high fat and high caloric diet. After the disease was successfully induced, the model rats were then randomized into three groups： the model control group （n = 15 ）, the Berberine group （n = 15 ） and the metformin group （n = 15 ）. Meanwhile 15 normal rats were assigned as the normal control group. The Berberine group was administrated with Berberine 180 mg/（kg · d） for 30 days, the metformin group was administrated with meuormm 180 mg/（ kg · d） for 30 days. At the end of the experiment, blood sample was collected and centrifugalized. Bloodsugar, serum insulin, CRP, IL-6 and TNF-α were measured and compared, and ISI was calculated. The pathological changes in β cells were observed under light microscope and electron microscope. Results Compared with rats in the normal control group, bloodsugar, serum insulin, CRP, IL-6 and TNF-α in rats of the model control group were significantly higher （ P 〈 0.05 ）. Compared with model control group, these indexes in Berberine group and metformin group were significantly lower （ P 〈 0.05 ）. No significant index difference between the Berberine group and the metformin group was found （ P 〉 0.05 ）. HE staining of pancreatic tissue showed that Berberine could ameliorate pancreatic injuries such as decreased pancreatic islets, deformed pancreatic cells, degranulation, collapse or absence of β cells. Immunohistochemistry study of β cell also confirmed this observation. Conclusion by decreasing the level of inflammatory mediators Berberine can lower bloodsugar and ease insulin resistance （CPR, IL-6, TNF-α） in type 2 diabetic r