吡格列酮对DM2大鼠肝脏及MCP-1表达的影响

Effect of Pioglitazone on Liver and MCP-l Expression in Type 2 Diabetic Rats

目的:观察吡格列酮对2型糖尿病(Type 2 diabetes mellitus,DM2)大鼠血、尿单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)表达及肝脏组织结构和功能的影响。方法:正常对照组(NC组)以普通饲料喂养;DM2 SD大鼠模型采用高糖高脂饲料喂养联合小剂量链脲佐菌素(streptozotocin,STZ)注射的方法建立。将模型组大鼠随机分为糖尿病组(DM组)和吡格列酮组(PIO组),后者采用吡格列酮对PIO组大鼠进行干预治疗。8周后检测血糖、糖化血红蛋白(HbA1c)水平、生化指标及肝脏组织病理的改变情况,同时检血、尿MCP-1水平、尿白蛋白/尿肌酐(urinary albumin/creatinine ratio,ACR)、尿视黄醇结合蛋白(urinaryretinol binding protein,URBP)的变化。结果:与NC组比较,DM组和PIO组第8周空腹血糖及HbAlc水平均明显升高,但DM组及PIO组间差异无统计学意义(P>0.05);第8周DM组与PIO组的尿ACR、URBP、血及尿MCP-1和肝脏纤维化程度均高于NC组(P<0.05),而PIO组4项指标较DM组明显降低,且UMCP-1与ACR呈正相关;病理显示,PIO组大鼠肝脏病变程度均较DM组明显减轻,肝组织MCP-1表达减少。结论:吡格列酮对DM2大鼠肝脏有明显的保护作用,其保护作用是独立于降糖作用之外的。其机制可能与其抑制肝组织MCP-1表达及其合成有关。

Objective To observe the effect of pioglitazone on monocyte chemoattractant protein-1 （MCP-I） level in the serum and urine, on MCP-1 expression in the liver, and on liver constitution and function in type 2 diabetic （DM2） rats. Methods The normal control group （ NC group） fed with normal diet. The model of DM2 rat was established by fed with high-sucrose-high-fat diet and injected low dose of strep tozotocin （STZ）. For the pioglitazone （PIO） group, the DM2 rats received PIO intervention. After 8 weeks, blood glu-cose levels, glycated hemoglobin Alc（HbAlc）, biochemical regular indices, and liver pathological changes were examined, the serum and urinary MCP-1 index , urinary albumin / creatinine ratio （ACR）, and urinary retinol binding protein （URBP） were also detected. Results Compared with the NC group, fasting blood glucose and HbAlc were obviously increased in the diabetes group （DM group）. There was no significant difference between the DM group and the PIO group. The ACR, URBP , UMCP-I ,and the degree of hepatic fi- brosis in the DM and the PIO group were higher than those in the NC group（ P 〈 0. 05）. Whereas the four above mentioned indicators were notably lower in the PIO group compared with the DM group. The UMCP-1 positively correlated with ACR, URBP. Pathological re- suhs showed that the extent of liver disease in the PIO group was significantly reduced and MCP-1 expression was decreased, compared with that in the DM group. Conclusion Pioglitazone has protective effect on the kidney in type 2 diabetic rat, which is independent on the hypoglycemic effect. It may be related to the inhibitory effect on MCP-1 expression and synthesis.