摘要
目的 探讨噻唑烷二酮类药吡格列酮对糖尿病 (DM )大鼠肾脏中转化生长因子 β1(TGF β1)及Ⅳ型胶原 (CⅣ)蛋白表达的作用。 方法 5 4只SD大鼠分为正常对照组 (NC组 ) ;糖尿病组 (DM组 ) :链脲佐菌素 70mg/kg腹腔注射 ;吡格列酮治疗组 (DP组 ) :吡格列酮 2 0mg·kg-1·d-1灌胃。检测各组第 2、4、8周的尿白蛋白排泄率 (UAER)及肾脏肥大指数 ,免疫组化观察肾皮质内TGF β1和CⅣ 表达水平。 结果 DM组及DP组TGF β1及CⅣ 表达显著高于NC组 (P <0 0 1) ,DP组TGF β1低于DM组 ,在第 4周差异有显著意义 (P <0 0 5 ) ,DP组CⅣ 亦低于DM组 ,在第 4、8周时差异均有显著意义 (P <0 0 5 )。DP组的UAER、肾脏肥大指数 ,在各时段均略低于DM组 ,但未达到统计学意义。 结论 DM大鼠肾脏中TGF β1及CⅣ 表达增加 ,吡格列酮可能通过下调TGF β1,减少CⅣ 细胞外基质合成增加 。
Objective To investigate the effect of pioglita zo ne on the expression of transforming growth factorβ 1(TGF-β 1 )and type Ⅳ collagen (C Ⅳ) in kidney of diabetic rats. Methods 54 Sprag ue-Dawley rats were randomized into 3 groups:normal control rats (group NC), st reptozotocin(STZ) induced diabetic rats(group DM) and diabetic rats treated with pioglitazone(group DP). Urinary albumin excretion and kidney hypertrop hy index were measured after 2,4,8 weeks of treatment,while TGF-β 1 and C Ⅳ expression in kidney cortex were observed by immunohistochemistry. Results The expression of TGF-β 1 and C Ⅳ were elevated in kidney of group DM and group DP(P<0.01). TGF-β 1 expression in group DP was si gnificantly lower than that in group DM at 4 weeks(P<0.05),while C Ⅳ was significantly lower than that in group DM at the 4 and 8 weeks(P<0.05) . Urinary albumin excretion and kidney hypertrophy index of group DP were slightly lower (P>0.05) than those of group DM at all time points. Conclusions There are increased expression of TGF-β 1 and C Ⅳ in kidney of STZ induced diabetic rats. Pioglitazone probably has some protec ting effect on diabetic kidney by inhibiting the expression of TGF-β 1 an d decreasing the synthesis of C Ⅳ.
基金
浙江省自然科学基金 ( 3 0 0 5 0 6)
浙江省卫生厅科研基金 ( 2 0 0 2A0 3 8)