联合用药延缓阿霉素肾病大鼠肾间质纤维化的研究

山东大学学报(医学版)

联合用药延缓阿霉素肾病大鼠肾间质纤维化的研究

李锋¹，甄军辉²，范晓红¹，江蓓¹，李宪花¹，郭玲¹，胡昭¹

山东大学齐鲁医院 1. 肾内科; 2.病理科, 山东济南 250012

收稿日期:2007-04-13 修回日期:1900-01-01 出版日期:2007-06-24 发布日期:2007-06-24
通讯作者: 胡昭

Combination drugs delay renal interstitial fibrosis of rats with Adriamycin nephropathy

LI Feng¹，ZHEN Jun-hui²，FAN Xiao-hong¹，JIANG Bei¹，LI Xian-hua¹，GUO Ling¹，HU Zhao¹

1. Department of Nephrology; 2. Department of Pathology， Qilu Hospital of Shandong University， Jinan 250012， Shandong, China

Received:2007-04-13 Revised:1900-01-01 Online:2007-06-24 Published:2007-06-24
Contact: HU Zhao

摘要/Abstract

摘要： 目的：探讨贝那普利和蝙蝠蛾拟青酶Cs-4联合应用对阿霉素肾病模型大鼠肾纤维化的保护作用及调节机制。方法：将60只SD大鼠随机分为模型组（M组）、贝那普利组（B组）、联合治疗组（U组）3组，每组20只。8周后观察各组大鼠24h尿蛋白定量、血脂、血浆总蛋白（TP）、血浆白蛋白(ALB)、尿素氮(BUN)、肌酐(Scr)的水平及肾脏病理改变，免疫组化检测肾层粘连蛋白（LN）、肾组织中纤连蛋白(FN)、胶原蛋白Ⅳ(Col Ⅳ)、转化生长因子β1(TGF-β1)的表达，RTPCR方法测定肾皮质转化生长因子β1（TGF-β1）和纤溶酶原激活物抑制物（PAI-1）、组织性金属蛋白酶抑制物1(TIMP1)mRNA的表达。结果：U组、B组分别和M组相比，24h尿蛋白定量、BUN、Scr、甘油三脂(TG)、总胆固醇(Cho)明显降低（P＜0.01），TP和ALB明显升高（P＜0.01）,U组和B组相比，BUN、Scr、TG、Cho亦明显降低（P＜0.05）；M组肾脏病理肾间质纤维化较重，而B组较轻，U组最轻；免疫组化可见B组和U组中LN、FN、Col Ⅳ、TGF-β1的表达明显低于M组（P＜0.01），并且U组和B组相比，Col Ⅳ、TGF-β1的表达明显降低（P＜0.05）；RTPCR显示B组、U组TGF-1mRNA、PAI-1mRNA、TIMP-1mRNA的表达，均较M组降低（P＜0.01），U组较B组亦明显降低（P＜0.05）。结论：蝙蝠蛾拟青酶Cs-4和贝那普利联合应用有相加作用，能有效的延缓肾间质纤维化。

关键词: 肾间质纤维化, 蝙蝠蛾拟青酶Cs-4 , 阿霉素肾病

Abstract: Objective: To investigate the protective effect and regulating mechanism of Benazepril combined with Paecilomyces hepiali Chen on rats with renal interstitial fibrosis. Methods: Rats were randomly divided into three groups： the model group(M group), the Benazepril group(B group) and the combination drugs group(U group). 24hour urinary protein excretion and renal function were determined at 8 weeks． Renal pathology and immunohistochemistry were assayed to measure the expression of fibronectin(FN)， collagenⅣ(ColⅣ)， and the transformor growth factorβ1(TGF-β1)． RT-PCR was used to examine the TGF-β1 mRNA, plasminogen activator inhibitor-1(PAI-1)mRNA, and tissue inhibitors of metalloproteinase-1(TIMP-1)mRNA. Results: Combination drugs and Benazepril effectively reduced the levels of 24hour urinary protein excretion, Bun, Scr, TG and Cho（P＜0.01）, but the levels of TP and ALB were significantly increased（P＜0.01）compared with the M group. Furthermore, the levels of BUN, Scr, TG and Cho were also significantly reduced in the U group compared with the B group（P＜0.05）. The levels of 24hour urinary protein excretion, Bun, Scr, TG and Cho were significantly decreased（P＜0.01） and the expression of LN, FN, ColⅣ, TGF-β1, TIMP-1 and PAI-1 was decreased by the combination drugs. Conclusions: Paecilomyces hepiali Chen combined with Benazepril can effectively delay the development of renal interstitial fibrosis.

Key words: Adriamycin nephropathy, Renal interstitial fibrosis, Paecilomyces hepiali Chen

中图分类号:

R692

李锋,甄军辉,范晓红,江蓓,李宪花,郭玲,胡昭 . 联合用药延缓阿霉素肾病大鼠肾间质纤维化的研究[J]. 山东大学学报(医学版), 2007, 45(6): 599-603.

LI Feng,ZHEN Jun-hui,FAN Xiao-hong,JIANG Bei,LI Xian-hua,GUO Ling,HU Zhao. Combination drugs delay renal interstitial fibrosis of rats with Adriamycin nephropathy[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(6): 599-603.

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