氨基胍、牛蒡对糖尿病大鼠肾脏组织非酶糖化和细胞凋亡的影响

The effect of amioguanidine and arctium lappa on renal tissue nonenzymatic glycation and apoptosis in diabetic rats

目的探讨非酶糖化与糖尿病肾病(DN)的关系,以及非酶糖化抑制剂氨基胍和具有非酶糖化抑制作用的牛蒡干预治疗对DN的治疗作用。方法雄性Wistar大鼠40只,随机分为4组,正常对照组、糖尿病组、糖尿病氨基胍(100mg·kg-1·d-1)治疗组(氨基胍组)、糖尿病牛蒡(150mg·kg-1·d-1)治疗组(牛蒡组),除正常对照组外,其他3组腹腔注射链脲佐菌素诱发糖尿病。16周后,处死大鼠,分离肾脏,测定组织非酶糖化,取部分肾脏皮质电镜观察细胞凋亡的形态学变化。结果治疗16周结束时,糖尿病各组大鼠体质量低于正常对照组(P<0.01),糖尿病各组间体质量比较差异无统计学意义(P>0.05);血糖水平均高于正常对照组(P<0.01);氨基胍组和牛蒡组血糖与治疗前比较,差异无统计学意义(P>0.05);糖尿病组大鼠肾组织肾皮质糖化终产物(AGEs)含量高于正常对照组(P<0.01),氨基胍组和牛蒡组AGEs含量低于糖尿病组(P<0.01),氨基胍组和牛蒡组比较差异无统计学意义(P>0.05)。透射电镜下见糖尿病组肾脏肾小管上皮细胞呈典型的凋亡形态学改变,氨基胍组和牛蒡组大鼠肾组织细胞凋亡改变明显减轻。糖尿病组肾小球基底膜增厚,系膜区域扩大。结论非酶糖化抑制剂氨基胍、牛蒡通过抑制非酶糖化、抑制细胞凋亡,明显改善糖尿病大鼠肾脏结构与功能,延缓DN的发展。

Objective To study the relationship between tissue nonenzymatic glycation and diabetic nephropathy（DN）,and explore the treatment effect of amioguanidine and arctium lappa in DN.Methods 40 male Wistar rats were randomly divided into following groups：control group,diabetic group,diabetic group treated with aminoguanidine（100mg·kg-1·d-1）,diabetic group treated with arctium lappa（150mg·kg-1·d-1）.These rats were induced hyperglycemia by intraperitoneal injection of streptozotocin.In the end of 16 weeks treatment,the rats were sacrificed and to measure renal tissue nonenzymatic glycation and to observe apoptosis by transmission electron microscope.Results The end of 16 weeks of treatment,body weight of diabetic group was lower than that of control group（P0.01）;Body weight among the diabetic groups was no significant difference（P0.05）.Blood glucose of diabetic group were higher than that of control group,the difference were statistically significant（P0.01）;Blood glucose of two treatment groups compared with before treatment,the difference was no statistically significant（P0.05）.Renal tissue AGEs in diabetic group was higher than that of control group（P0.01）,AGEs content of the two treatment groups was lower than that of diabetic group（P0.01）,treatment groups was no significant（P0.05）.The renal apoptosis changes of diabetic group were observed in transmission electron microscope and those morphology changes was lessening in two treatment groups.The glomerular basement membrane of diabetic group was thickening and mesangial region was enlarged,and was lessen in treatment groups.Conclusion Aminoguanidine and arctium lappa can inhibit the cell apoptosis,improve the kidney structure and function of diebetic rats,then to delay the development of DN.