川芎嗪联合贝那普利对GK大鼠肾间质巨噬细胞浸润及肿瘤坏死因子-α表达的影响

Effect of tertramethylpyrazine combined with benazepril on tubulointerstitial macrophage infiltration and tumor necrosis factor-α in GK rats

目的观察川芎嗪联合贝那普利对GK大鼠肾间质巨噬细胞(ED-1)浸润及肿瘤坏死因子-α(TNF-α)表达的影响。方法将造模成功的GK大鼠随机分为模型组、贝那普利组、川芎嗪组、川芎嗪+贝那普利组,另设Wistar大鼠为正常对照组,共计5组,分别予生理盐水、贝那普利、川芎嗪、川芎嗪联合贝那普利灌服,共16周。实验第0、12、16周监测空腹血糖(FBG);实验第8、12、16周测定24小时尿蛋白定量;16周后,免疫组化法(IH)检测肾间质中ED-1、TNF-α表达。结果模型组大鼠24小时尿蛋白定量较正常组明显升高(P<0.01),肾间质中ED-1浸润及TNF-α表达明显增加(P<0.01);各治疗组24小时尿蛋白含量均不同程度降低(P<0.05或P<0.01),肾间质ED-1浸润及TNF-α表达降低(P<0.05)。结论川芎嗪联合贝那普利能够改善GK大鼠肾脏功能,减轻肾间质病变,其机制可能与降低蛋白尿排泄、减轻肾间质ED-1浸润,下调TNF-α等的表达有关。

Objective To observe the effect of Tertramethylpyrazine （TMP） combined with Benazepril on tubulointerstitial macrophage infiltration and the expression of tumor necrosis factor-α （ TNF-α） in the renal interstitium of GK rats. Methods After being successfully modeled, GK rats were randomized into 4 groups ： model group, Benazepril group, TMP group, TMP combined with Benazepril group. Wistar rats were set as normal group. Except the rats in normal group and model group were treated with physiological saline, other rats received corresponding medicines according to the experimental design for 16 weeks. Random blood glucose （RBG） was examined at baseline, 12th and 16th week. Volume of urine protein within 24 hours was examined in the 8th, 12th and 16th week. At the end of the 16th week, the expression of TNF-α and ED-1 in renal tubulointerstitium was detected by immunohistochemistry. Results Compared with normal group, the volume of 24h urine protein rised obviously （ P 〈 0. 05 ） in the model group,so was the expression of TNF-αand ED-1 in renal tubulointerstitium （ P 〈 0. 01 ）. Each therapeutic group can reduce the volume of 24h urine protein at different levels（ P 〈 0.05 or P 〈 0. 01 ） ,and can decrease the expression of TNF-α and ED-1 in renal tubulointerstitium （ P 〈 0. 05 ）. Conduslons TMP combined with Benazepril can improve renal function and reduce interstitial pathological changes of GK rats. The mechanism may be related to decreasing excretion of proteinuriay alleviating tubulointerstitial macrophages infiltration and downregulating the expression of TNF-α in renal interstitium.