黄芪三七合剂通过影响p38 MAPK的表达改善CKD大鼠肾脏纤维化

The effects of astragalus and radix notoginseng on kidneys in CKD rats via p38 MAPK signal pathway

目的探讨黄芪三七合剂通过调控p38 MAPK的表达改善慢性肾脏疾病(CKD)大鼠肾脏纤维化的作用。方法将雄性SD大鼠60只分为3组:健康组(NOR,n=20)、模型组(CKD,n=20)、黄芪三七合剂组(A&R,n=20)。CKD组和A&R组采用腺嘌呤灌胃方法建立大鼠CKD模型,建模后A&R组予以黄芪三七合剂(3mL/d)灌胃,NOR组和CKD组予以同等体积生理盐水灌胃,连续4周。于建模后2、4周分别处死各组大鼠10只,检测肾功能,行肾脏HE和Masson染色观察肾脏病理及纤维化改变;免疫组织化学法测定肾脏p38 MAPK蛋白表达水平。结果与NOR组相比,CKD组的血尿素氮及血肌酐水平均显著升高(P<0.01),与CKD组比较,A&R组大鼠肾功能指标明显改善(P<0.05)。CKD组大鼠肾脏出现肾小管管腔扩张,坏死,大量炎性细胞浸润,大量肾间质纤维化及肾间质胶原沉积的改变,与CKD组比较,A&R组肾脏病理损害减轻,胶原沉积面积比明显减少(P<0.05)。免疫组织化学结果提示CKD组和A&R组的p38 MAPK蛋白表达均显著高于NOR组(P<0.01),而A&R组低于CKD组(P<0.05)。结论黄芪三七合剂对大鼠肾脏损伤具有保护作用,其改善纤维化的作用可能是通过减弱p38MAPK蛋白表达发挥。

Objective To investigate the effects of astragalus and radix notoginseng on the renal fibrosis in rats with chronic kidney disease（CKD）by regulating the p38 MAPK signaling pathway.Methods Sixty rats were divided randomly into three groups,which were NOR group,CKD group and AR group.All the rats in CKD group and AR group were given adenine by gavage.AR group received AR（3mL/d）;the NOR group and CKD group received corresponding amount of saline.Renal function was examined with automatic biochemical analyzer;renal pathological damage was detected with HE staining and Masson staining;the expression of p38 MAPK was assessed with immunohistological staining.Results The level of serum creatinine and blood urea nitrogen in CKD group were significantly higher than NOR group（P〈0.01）,and in AR group was lower than CKD group（P〈0.05）.Various degrees of luminal expansion,degeneration and necrosis,and interstitial inflammatory cell infiltration and congestion as well as edema appeared in renal tubules in CKD groups.And the collagen volume in AR group was higher than those in NOR group（P〈0.05）.The expression ratio of p38 MAPK in CKD group and AR group was both much higher than those in NOR group（P〈0.01）,but the expression in AR group was significantly lower than those in CKD group（P〈0.05）.Conclusion The astragalus and radix notoginseng has a significant protective effect on kidney disease,the mechanism of which may inhibit the activation of p38 MAPK,thus improving fibrosis of kidneys.