白细胞介素-10和肿瘤坏死因子-α在肾小球硬化模型大鼠中的表达与意义

Expression and implication of IL-10 and TNF-α in model rats of glomerulosclerosis

目的观察白细胞介素(IL)-10和肿瘤坏死因子(TNF)-α在肾小球硬化模型大鼠中的表达,探讨其与肾小球硬化发生的关系。方法将20只SPF级雄性SD大鼠随机分为正常组(5只)、假手术组(5只)和模型组(10只)。模型组于大鼠右背行右肾切除术,术后第7天,尾静脉注射阿霉素(ADR)5 mg/kg,间隔21 d后再次注射ADR 3 mg/kg,建立大鼠肾小球硬化模型;假手术组剥离右肾包膜,尾静脉注射等剂量生理盐水;正常组仅尾静脉注射等剂量生理盐水。分别于术后1,3,5,7,9,11周检测24 h尿蛋白定量;于术后11周心脏采血处死大鼠,采用全自动生化分析仪检测血清尿素氮(BUN)、肌酐(Scr),并计算大鼠脾脏指数(SI)、胸腺指数(TI);采用ELISA法检测血清IL-10,TNF-α;HE染色观察肾脏病理改变,并计算肾小球硬化指数(GSI)。结果与正常组比较,假手术组各项指标均无明显变化,差异无统计学意义(P>0.05);与正常组和假手术组比较,模型组造模后大鼠体质量、SI、TI、血清IL-10表达量显著降低,24 h尿蛋白定量、GSI、血清BUN及Scr含量、血清TNF-α表达量显著升高,差异均有统计学意义(P<0.05)。病理结果显示,模型组肾小球呈局灶节段性硬化,间质内有明显淋巴细胞浸润,并有纤维化。结论大鼠肾小球硬化的发生与I L-10和TNF-α的异常表达有关。

Objective To observe the expression of IL-10 and explore their correlativity. Methods 20 male SD rats were randol cases） ,sham-operated group （5 cases） and model group （10 cases）. The in model rats of glomerulosclerosis and ed into three groups： normal group （5 models were established by adriamyein （ADR） injection with unilateral nephropathy and were injected ADR again after 21 days; the sham-operated group was injected saline with decapsulation of kidney; the normal group was only injected equal saline. 24 h urinary pro- tein was detected respectively on 1^st ,3^rd ,5^th ,7^th ,9^th and 11^th week after operation; the rats were killed with blood- collecting from heart and spleen index （ SI）, thymus index （TI） were detected at the end of 11^th week, BUN and Scr in serum were examined by automatic biochemistry analyzer; IL-10,TNF-ot in serum were measured by ELISA; re- nal pathological changes were observed by HE staining as well as GSI was calculated. Results All indexes bad no statistical significance between sham-operated group and normal group （P〉0.05）. Compared with normal group and sham-operated group, body weight, SI ,TI and IL-10 in model group decreased （P〈0.05） ; the results of 24 h urinary protein, GSI, BUN, Scr and TNF-a increased, the differences were significant （P 〈 0.05 ）. In the model group, the pathological results showed that the glomerulus had focal segmental sclerosis and there were obvious lym- phocyte infiltration and fibrosis in the interstitial. Conclusion The occurrence of glomerulosclerosis in rats is rela- ted to the abnormal expression of IL-10 and TNF-α.