抗纤灵方对阿霉素肾病大鼠肾纤维化作用机制的研究  

Mechanism of Kangxianling Decoction on renal fibrosis in rats with adriamycin nephropathy

作　　者：蒋宇峰[1,2] 朱尧焓 唐英 何立群[1,2] JIANG Yufeng;ZHU Yaohan;TANG Ying;HE Liqun(Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021,China;Shanghai Key Laboratory of Clinical Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院西院肾内科,上海200021 [2]上海市中医临床重点实验室,上海201203

出　　处：《上海中医药杂志》2018年第12期72-77,共6页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81473626)

摘　　要：目的观察抗纤灵方对阿霉素肾病模型大鼠肾纤维化的作用机制。方法将SD雄性大鼠随机分为7组,每组8只。其中正常组不做处理,假手术组仅于右侧肾切除,注射0.9%NaCl溶液,余下40只SD大鼠均采取右侧肾切除加尾静脉注射阿霉素制备大鼠阿霉素肾病模型。将造模成功后的大鼠分成模型组,科素亚组,抗纤灵低、中、高剂量组,分别给予相应药物共8周。观察大鼠血清肌酐、尿素氮、24 h尿蛋白定量、α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)表达,HE染色观察肾组织病理。结果抗纤灵方能抑制模型大鼠α-SMA的表达,并减少FN的生成,差异有统计学意义(P<0.05);同时降低24 h蛋白尿,降低血清肌酐、尿素氮,改善肾功能,延缓肾纤维化发展,差异有统计学意义(P<0.05);随着抗纤灵剂量增加,其抗纤维化效应更明显,差异有统计学意义(P<0.05)。结论抗纤灵方能降低24 h尿蛋白定量,改善肾功能,使肾脏病理组织形态学改善,并且呈剂量效应。其机制可能是通过下调α-SMA的表达,抑制FN的生成,从而改善肾纤维化。Objective To observe the mechanisms of Kangxianling Decoction on renal fibrosis in rats with adriamycin nephropathy. Methods SD male rats were randomly divided into 7 groups,8 rats in each group. The normal group was treated with no surgery,and the sham operation group was treated with 0.9% NaCl solution after right nephrectomy. The other 40 SD rats were treated with right nephrectomy and intravenous injection of adriamycin to establish the adriamycin nephropathy model. After successful modeling,the model rats were randomly divided into the model group,Cozaar group,Kangxianling Decoction groups with low- ,medium-and high-dose. The rats were treated with the corresponding drugs for 8 weeks. The serum creatinine,urea nitrogen,24 h urinary protein excretion, mRNA expressions of α-smooth muscle actin (α-SMA) and fibronectin (FN) in kidney tissue were detected,and the renal pathology was observed after HE staining. Results Compared with the model group,the α-SMA expression and the FN level were significantly decreased in Kangxianling Decoction group,with statistically significant differences (P<0.05) . Meanwhile,the levels of 24 h urinary protein excretion,serum creatinine and urea nitrogen were decreased after Kangxianling Decoction treatment,the renal function was improved and the development of renal fibrosis was delayed,with statistically significant differences (P<0.05) . The anti-fibrosis effects of Kangxianling Decoction was enhanced with the increase of dosage,with statistically significant differences (P<0.05) . Conclusion Kangxianling Decoction can decrease 24 h urinary protein excretion,improve the renal function and pathological histomorphology in a dose-dependent manner. Its mechanism on improving renal fibrosis may be down-regulating the expression of α-SMA and inhibiting the production of FN.

关 键 词：抗纤灵方 肾纤维化 阿霉素肾病 大鼠 

分 类 号：R285.5[医药卫生—中药学]