摘要
目的探讨中药复方抗纤灵治疗阿霉素诱导的大鼠肾纤维化的作用及机理。方法雄性SD大鼠45只随机分为4组,正常组(7只)、假手术组(8只)、模型组(15只)、抗纤灵治疗组(15只)。用单侧肾切除并2次阿霉素诱导法建立大鼠肾纤维化模型,手术第4周和第8周检测尿素氮、血肌酐含量和内生肌酐清除率等指标,同时称量大鼠体重;抗纤灵治疗72天后取肾组织,HE染色、六胺银染色和免疫组化观察肾组织病变;采用Western印迹分别检测转化生长因子β受体Ⅰ(TβRⅠ)、转化生长因子β受体Ⅱ(TβRⅡ)、Smad2、Smad7的蛋白表达。结果与正常组比较,模型组大鼠尿素氮、肌酐均有明显上升,内生肌酐清除率下降;模型组大鼠肾小球基底膜增厚、节段性硬化和玻璃样变,硬化的肾小球周围所属肾小管萎缩,部分肾小管消失;部分肾小球肥大,周围肾小管扩张严重;肾小球集中现象明显;肾小管上皮细胞变性,蛋白管型严重;肾间质纤维组织增生和大量炎细胞浸润。模型组肾组织TβRⅠ、Smad2蛋白表达显著上调,而TβRⅡ、Smad7蛋白表达水平无明显变化。中药干预后,血尿素氮及血肌酐含量显著降低,内生肌酐清除率有所升高。抗纤灵治疗组大鼠的上述病理改变明显轻于模型组,肾组织TβRⅠ、Smad2蛋白表达明显减少。结论抗纤灵可抑制肾组织TβRⅠ、Smad2蛋白表达,从而改善阿霉素诱导的肾纤维化及肾功能。
Objective To study the effect and mechanism of Kangxianling （KXL, a Chinese compound recipe） in treating adriamycin （ADR） induced renal fibrosis rats. Methods Forty-five male SD rats were randomly divided into 4 groups, the normal group （ n = 7）, the sham operative group （ n = 8）, the model group （ n = 15）, and the treatment group （n = 15）. Model of renal interstitial fibrosis was established in rats by unilateral nephrectomy and intravenous injection of ADR twice at a 30-day interval, and the rats in the treatment group treated with KXL once a day for 72 days. Body weight, serum creatinine （SCr）, blood urea nitrogen （BUN） levels and endogenous creatinine clearance rate （CCr） of animals were analyzed at the end of the 4th and the 8th week after operation. Rats were sacrificed after 72 days of treatment and their kidney obtained for pathological examination with HE and PASM staining. And protein expression levels of transforming growth factor β（TGF-β） receptor Ⅰ （TβRⅠ ）, TGF-i3 receptor Ⅱ （TβRⅡ ）, Smad2 and Smad7 were determined by Western blotting. Results Levels of SCr and BUN in animals of the model group were significantly higher and CCr lower than those in the normal group （P 〈 0.05）. Pathological examination of kidney in the model group showed thickened glomerular/tubular basement membrane with segmental sclerosis and hyaline degeneration; atrophy of the renal tubule around the sclerotic glomeruli and part of them disappeared; hypertrophy of partial glomeruli with sur-rounding severe dilated tubules; obvious glomeruli centering phenomena; severe tubular epithelial cell degeneration, necrosis with protein cast; fibrous tissue proliferation and large amount of inflammatory cell interstitial infiltration. The protein expression of TβRⅠ and Smad2 in kidney tissue of the model group were significantly upregulated, while that of TβRⅡ and Smad7 unchanged. After KXL intervention, level of BUN lowered, SCr tended to normal and the endogenous SCr was raised to some degree. The renal pathological status in the treatment group was significantly improved and with markedly lowering of TβRⅠ and Smad2 protein expression. Conclusion KXL could inhibit the protein expression of TβRⅠ and Smad2 in kidney tissue, so as to alleviate the renal fibrosis induced by adriamycin and improve the renal function.
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2007年第12期1094-1098,共5页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金(No.30371834)
上海市高等学校科学技术发展基金项目(No.02CK10)
上海市重点学科建设资助项目(No.Y0302)
作者简介
通讯作者：张悦，Tel：021-51322391，E-mail：yuezhang-shanghai@yahoo．com．cn
