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目的:观察吡格列酮对2型糖尿病(Type 2 diabetes mellitus,T2DM)大鼠血、尿单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)表达及肾脏组织结构和功能的影响。方法:正常对照组(NC组)喂以常规饲料;采用高糖高脂膳食、小剂量链脲佐菌素(streptozotocin,STZ)注射的方法建立2型糖尿病大鼠模型,将成模的大鼠随机分为糖尿病(DM组)和吡格列酮(PIO组),后用吡格列酮对PIO组大鼠进行干预治疗。8周后检测血糖水平、尿生化结果、肾脏组织病理的改变情况,同时检测尿MCP-1指标的变化。结果:与NC组比较,DM组和PIO组第8周空腹血糖及糖化血红蛋白水平均明显升高,但DM组、PIO组间差异无统计学意义(P<0.05);第8周DM组、PIO组尿白蛋白/尿肌酐(urinary albumin/creatinine ratio,ACR)、尿视黄醇结合蛋白(urinary retinol binding-pro-tein,URBP)、尿MCP-1(urinary monocyte chemoattractant protein-1,UMCP-1)和肾脏肥大指数均高于NC组,PIO组4项指标较DM组明显降低,且UMCP-1与ACR,URBP及肾脏肥大指数呈正相关;病理显示PIO组大鼠肾小球病变程度均较DM组明显减轻,MCP-1表达减少。结论:吡格列酮对2型糖尿病大鼠肾脏有明显的保护作用,这种保护作用是独立于降糖作用之外的。其机制可能与其抑制肾组织MCP-1表达及其排泄有关。
Objective: To observe the effects of pioglitazone on the expression of monocyte chemoattractant protein-1 (MCP-1) and the structure and function of kidney in type 2 diabetes mellitus (T2DM) rats. Methods: The normal control group (NC group) was fed with normal diet. The model rats with type 2 diabetes were established by injecting low-dose high-sugar and high-fat diet and low dose streptozotocin (STZ) Divided into diabetes (DM group) and pioglitazone (PIO group), after pioglitazone intervention in the PIO group of rats. After 8 weeks, blood glucose level, urine biochemical result and renal histopathological changes were detected, and the changes of urine MCP-1 index were also detected. Results: Compared with NC group, the levels of fasting blood glucose and glycosylated hemoglobin in DM group and PIO group were significantly increased at the 8th week, but there was no significant difference between DM group and PIO group (P <0.05) Urinary albumin / creatinine ratio (ACR), urinary retinol binding-pro-tein (URBP), urinary monocyte chemoattractant protein-1 (UMCP- 1) and renal hypertrophy index were higher than NC group, 4 indicators of PIO group was significantly lower than DM group, and UMCP-1 and ACR, URBP and renal hypertrophy index were positively correlated; pathological findings of PIO group glomerular lesions were Compared with DM group, the expression of MCP-1 decreased significantly. Conclusion: Pioglitazone significantly protects the kidneys of type 2 diabetic rats. This protective effect is independent of the hypoglycemic effect. The mechanism may be related to its inhibition of renal tissue MCP-1 expression and its excretion.