丹酚酸B对糖尿病血糖波动模型大鼠胰岛细胞的保护作用

Protective effect of salvianolic acid B on pancreatic islet cells in diabetic rats with fluctuating blood glucose

目的观察丹酚酸B对糖尿病血糖波动模型大鼠胰岛细胞的保护作用,并探讨其可能的作用机制。方法采用高糖高脂饮食合并ip链脲佐菌素(STZ)的方法建立大鼠糖尿病模型,并在此基础上通过错时给予胰岛素或葡萄糖建立糖尿病血糖波动模型,丹酚酸B各组分别给予丹酚B 160、80 mg/kg。血糖波动6周后,检测大鼠空腹血糖(FBG)、空腹胰岛素(FINS)和糖化血红蛋白(GHb)水平,并检测大鼠血清和胰腺组织总抗氧化能力(TAC)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平,HE染色法观察大鼠胰岛组织病理学改变,TUNEL染色法检测大鼠胰岛细胞凋亡情况,Western blotting法检测胰腺组织胰十二指肠同源盒-1(PDX-1)蛋白表达水平。结果糖尿病大鼠FBG、GHb及血清和胰腺组织MDA水平较对照组明显升高,而FINS水平及血清和胰腺组织TAC、SOD活性显著下降(P<0.01)。同时,糖尿病大鼠胰岛数量减少,胰岛体积缩小,胰岛细胞凋亡明显增多(P<0.01),胰腺组织PDX-1蛋白表达水平显著下降(P<0.01)。给予丹酚酸B 6周后,大鼠FINS水平,血清及胰腺组织中TAC、SOD活性均明显升高,而FBG、GHb、血清及胰腺组织中MDA水平明显下降(P<0.05、0.01)。丹酚酸B明显改善大鼠胰岛病理学改变,减少胰岛细胞凋亡,增加PDX-1蛋白表达水平(P<0.05、0.01)。结论丹酚酸B可明显减轻糖尿病血糖波动模型大鼠胰岛病变,改善胰岛功能,其作用机制可能与改善氧化应激、上调PDX-1蛋白表达水平,进而抑制胰岛细胞凋亡有关。

Objective To observe the protective effect of salvianolic acid B（Sal B） on pancreatic islet cells in diabetic rats with fluctuating blood glucose and the possible mechanisms implicated. Methods Diabetes model in rats was established by feeding with high-sugar and high-fat diets combined with ip injection of streptozotocin（STZ）. Then the rats were subjected to ip injection of insulin and/or ig administration of glucose at indicated time for 6 weeks to induce blood glucose fluctuation, with those in Sal B groups ig supplemented with Sal B 160 or 80 mg/kg. The contents of fasting blood glucose（FBG）, fasting serum insulin（FINS）, and glycosylated hemoglobin（GHb） and the levels of total anti-oxidant capacity（TAC）, superoxide dismutase（SOD） activity, and malondialdehyde（MDA） in both serum and pancreatic tissues were determined with commercially available kits. Pathological changes and cell apoptosis in pancreatic islets were evaluated by HE staining and TUNEL staining, respectively. Protein levels of PDX-1 in pancreatic tissues were examined by Western blotting analysis. Results Compared with the control group, the contents of FBG, GHb, and MDA in diabetic rats were increased significantly, while the levels of FINS, TAC, and SOD activity were decreased markedly（P 〈 0.01）. Pancreatic islets in diabetic rats became decreased in size and number, while cell apoptosis in islets increased notably（P 〈 0.01）. Protein level of PDX-1 was significantly decreased in pancreas of diabetic rats（P 〈 0.01）. Supplementation with Sal B resulted in a significant decrease in FBG, GHb, and MDA contents and increase in FINS, TAC, and SOD activity in diabetic rats（P 〈 0.05, 0.01）. Sal B significantly attenuated pathological changes and reduced cell apoptosis in pancreatic islets of diabetic rats, with the expression of PDX-1 protein up-regulated evidently（P 〈 0.05 or 0.01）. Conclusion Sal B can significantly ameliorate pancreatic pathological changes and improve pancreatic islet function in diabetic rats with fluctuating blood glucose, which might be attributed to attenuation of oxidative stress, up-regulation of PDX-1 expression, and suppression of islet cell apoptosis.