消瘀泄浊饮对慢性肾衰竭营养不良大鼠残肾组织保护作用机制研究  

Study on the Mechanism of the Protective Effect of Xiaoyu Xiezhuo Decoction on Remnant Renal Tissue in Rats with Chronic Renal Failure and Malnutrition

作　　者：鲁科达[1] 张冰冰[2] 张培培[1] 何灵芝[1] 陈方明[2] 寿旗扬[2] 

机构地区：[1]浙江中医药大学附属第一医院,杭州310006 [2]浙江中医药大学

出　　处：《浙江中医药大学学报》2016年第2期137-142,共6页Journal of Zhejiang Chinese Medical University

基　　金：浙江省自然科学基金项目(LY12H27003)Fund project:Zhejiang Provincial Natural Science Foundation(LY12H27003)

摘　　要：[目的]观察消瘀泄浊饮对慢性肾衰竭(chronic renal failure,CRF)营养不良大鼠残肾组织基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶组织抑制因子-1(tissue inhibitor of matrix metalloproteinase-1,TIMP-1)及纤维连接蛋白(fibronectin,FN)、Ⅳ型胶原(collagenⅣ,ColⅣ)的影响。[方法]46只SD雄性大鼠,随机选取10只为正常组,其余大鼠采用5/6肾切除同时予以低蛋白饮食制作CRF营养不良大鼠模型,观察营养不良发生时间,随机分成模型组、复方ɑ-酮酸组(开同组)、消瘀泄浊饮组,每组12只,治疗4周后检测血肌酐(serum creatinine,Scr)、尿素氮(blood urea nitrogen,BUN)、白蛋白(albumin,ALB)水平,应用光学显微镜(HE染色)观察肾组织病理学变化,用免疫组化法检测残肾组织MMP-9、TIMP-1、FN、ColⅣ的表达。[结果]CRF大鼠在术后10周出现营养不良。与治疗后模型组比,消瘀泄浊饮组大鼠血清ALB明显增加(P<0.05),营养状况和肾功能明显改善(P<0.05),消瘀泄浊饮组对于肾功能的改善要优于开同组(P<0.05),消瘀泄浊饮组肾脏病理组织损害轻于开同组;与正常组比,模型组TIMP-1、FN、ColⅣ表达增强,MMP-9表达减少(P<0.05);与模型组比,消瘀泄浊饮组MMP-9的表达明显增强,TIMP-1、FN、ColⅣ表达明显减弱(P<0.05)。[结论]消瘀泄浊饮可通过上调MMP-9、下调TIMP-1表达,减少FN、ColⅣ在肾组织中沉积,从而起到保护CRF营养不良大鼠残肾组织的作用。[Objective]To observe the effect of Xiaoyu Xiezhuo Decoction on MMP-9, TIMP-1, FN, CollV of rats with chronic renal failure（CRF） and malnutrition（MN）. [Methods] 10 rats were randomly selected from the forty-six male SD rats as the normal group, the rest rats were established into CRF- MN by 5/6 nephrectomy and low protein diet, the happening time of MN in them was recorded. Rats successfully modeled were randomly divided into 3 groups： 12 rats in model group, 12 rats in control group treated with composite a-keto acid and 12 rats in Xiaoyu Xiezhuo Decoction treated group. After being treated for 4 weeks, serum creatinine（Scr）, blood urea nitrogen（BUN）, albumin were detected; renal histopathotogical changes were examined by light microscopy（HE staining）; immunohistochemistry was applied to measure the expression of MMP-9, TIMP-1, COIN, FN in remnant renal tissue. [Results] CRF rats revealed MN at the end of lOth week after modeling, after treatment, compared with the model group, the condition of MN and renal function of Xiaoyu Xiezhuo Decoction treated group was significantly impreved（P〈0.05）, The improvement in renal function and histopathological changes of Xiaoyu Xiezhuo Decoction treated group was better than control group; Compared with normal group, the model group had a significant higher level expression of TIMP-1, Col IV, FN, while the expression of MMP-9 decreased; compared with model group, the expression of MMP-9 of Xiaoyu Xiezhuo Decoction treated group increased, the expression of TIMP-1, Col, FN IV decreased significantly（P〈0.05）. [Conclusion] Xiaoyu Xiezhuo Decoction can decrease accumulation of FN, Col IV as well as protecting the remnant kidney function in rats with chronic renal failure and malnutrition by up-regulating of expression of MMP-9 and down-regulating of expression of TIMP-1 in renal tissues.

关 键 词：消瘀泄浊饮 慢性肾衰竭 营养不良 基质金属蛋白酶-9 基质金属蛋白酶组织抑制因子-1 纤维连接蛋白 Ⅳ型胶原 

分 类 号：R692[医药卫生—泌尿科学]