鲤鱼汤对阿霉素肾病大鼠肾脏MMP-2和TIMP-2表达的影响

Effect of cyprinus carpio decoction on the expression of MMP-2 and TIMP-2 in kidney of rats with adriamycin-induced nephropathy

目的探讨鲤鱼汤对阿霉素肾病的治疗作用及机制。方法选择40只Wistar大鼠,随机取10只作为对照组;其余30只尾静脉注射阿霉素6.2 mg/kg制作阿霉素肾病模型后随机分为模型组、厄贝沙坦组及鲤鱼汤组各10只。鲤鱼汤组以300%鲤鱼汤9 mL/kg灌胃,厄贝沙坦组以厄贝沙坦50 mg/kg灌胃,模型组及对照组以9mL/kg饮用水灌胃,均1次/d。每周收集一次12 h尿液,测尿蛋白定量。干预8周后处死大鼠,检测血清总蛋白(TP)、白蛋白(ALB)、尿素氮(BUN)、肌酐(Cr)水平,取肾组织行HE染色观察病理改变,免疫组化法检测肾组织基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶抑制剂-2(TIMP-2)表达。结果与对照组比较,模型组MMP-2与TIMP-2表达均降低,BUN、Cr升高,TP、ALB降低(P均<0.05),出现肾小管损害、肾小球体积增大;与模型组比较,鲤鱼汤组MMP-2和TIMP-2表达增加,肾小球截面积、肾小球体积及肾小管损害率降低,BUN、Cr降低,TP、ALB升高(P均<0.05)。结论鲤鱼汤对降低尿蛋白、缓解肾小球细胞外基质蓄积及肾脏纤维化有积极作用。其机制可能为调节MMP-2/TIMP-2平衡。

Objective To investigate the mechanism of cyprinus carpio decoction on adriamycin nephrosis. Methods A total of 40 male Wistar rats were involved in this study, of which 10 rats were divided into control group and the other 30 rats were injected by doxorubicin in a dose of 6.2 mg/kg through tail vein to induce adriamycin nephrosis model. The 30 adriamycin nephrosis model rats were then divided equally into 3 group which was named as model group, irbesartan group and cyprinus carpio decoction group. Rats in cyprinus carpio decoction group were intragastric administrated with 300% cyprinus carpio decoction in a dose of 9 mL/kg perday. Rats in irbesartan group were intragastric administrated with irbe- sartan in a dose of 50 mL/kg perday. Rats in model group and control group were intragastric administrated with water in a dose of 9 mL/kg perday. Urine in 12 hours of each group was collected weekly to measure urinary protein. All rats were killed after the intervening of 8 weeks to observe their pathological changes of kidney, detect TP, ALB, BUN, Cr and de- tect the expression of MMP-2 and TIMP-2 in kidney by method of immunohistochemistry. Results Compare with control group, the levels of MMP-2 and TIMP-2 of model group decreased, BUN and Cr increased, TP and ALB decreased （P 〈 0.05 ） , as well as interstitial fibrosis appeared, glomerular volume increased. Compared with model group, the levels of MMP-2 and TIMP-2 in eyprinus carpio decoction group increased, Cr and BUN decreased, TP and ALB increased（P 〈 0.05）. Conclusion Cyprinus carpio decoction was positive in the reduction of urinary albumin excretion rate, remission of glomerular extracellular matrix accumulate and renal fibrosis. The mechanism may be associated with the regulate balance of MMP-2/TIMP-2.