山药多糖对糖尿病肾病小鼠肾功能和醛糖还原酶通路的影响

Effects of Dioscorea opposita Polysaccharide on Renal Function and Aldose Reductase Pathway in Mice with Diabetic Nephropathy

目的:研究山药多糖对四氧嘧啶诱导的糖尿病肾病(DN)小鼠肾功能的保护作用及其对醛糖还原酶通路的影响。方法:采用腹腔注射四氧嘧啶方法复制DN小鼠模型。随机分为正常对照组、模型组、二甲双胍(0.1 g/kg)阳性对照组及山药多糖低(0.05 g/kg)、高(0.1 g/kg)剂量组。给药3 w后,检测小鼠血糖及血肌酐(Scr)、尿素氮(BUN)等肾功能指标;HE染色观察肾脏及胰腺组织形态学变化;Masson染色观察肾脏纤维化;Western blot法检测肾脏醛糖还原酶(aldose reductase,AR)、磷酸化P38丝裂原活化蛋白激酶(p-P38MAPK)、磷酸化cAMP反应元件结合蛋白(p-CREB)等蛋白表达。结果:与正常对照组比较,模型组小鼠血糖、Scr、BUN均显著升高(P<0.01);与模型组比较,各给药组小鼠血糖、Scr、BUN水平显著降低(P<0.05),胰腺和肾脏的病理损伤明显改善,胰岛体积和数目及肾小球肿胀和肾脏纤维化程度明显改善。与正常对照组比较,模型组小鼠肾脏AR、p-P38MAPK、p-CREB蛋白表达显著升高(P<0.01),与模型组比较,山药多糖低、高剂量组AR、p-CREB蛋白表达及高剂量组p-P38MAPK蛋白表达显著降低(P<0.01)。结论:山药多糖对DN小鼠肾功能有一定的保护作用,其机制可能与抑制高糖激活的AR/P38MAPK/CREB信号通路有关。

Objective:To investigate the protective effect of Dioscorea opposita polysaccharide on renal function and aldose reductase pathway in alloxan-induced diabetic nephropathy(DN)mice.Methods:The model of DN mice was replicated by intraperitoneal injection of alloxan.The DN mice were randomly divided into normal control group,model group,metformin positive control group(0.1 g/kg)and low and high dose Dioscorea opposita polysaccharide group(0.05,0.1 g/kg).The mice were given gavage for 3 w.The blood glucose and renal function parameters including serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.The morphological changes of kidney and pancreas were observed by HE staining.The renal fibrosis was observed by Masson staining.The protein expressions of AR,p-P38 MAPK and p-CREB were detected by Western blot.Results:Compared with the normal control group,the blood glucose,Scr and BUN of the model group were significantly increased(P<0.01).Compared with the model group,the blood glucose,Scr and BUN levels of the mice in each administrated group were significantly decreased(P<0.05).The pathological damage of pancreas and kidney were significantly improved.The volume and numbers of pancreas islet and the degrees of glomerular swelling and renal fibrosis were dramatically improved.Compared with the normal control group,the protein expressions of AR,p-P38 MAPK and p-CREB in model group were significantly increased(P<0.01).Compared with the model group,the protein expressions of AR,p-CREB in low and high dose Dioscorea opposita polysaccharide group and p-P38 MAPK protein in the high dose group were significantly decreased(P<0.01).Conclusion:Dioscorea opposita polysaccharide has a protective effect on renal function of DN mice,which may be related to inhibit the high glucose-activated AR/P38 MAPK/CREB signaling pathway.