苦参碱对腺嘌呤致大鼠肾小管-间质纤维化的影响

Effects of matrine on adenine-induced chronic tubulointerstitial fibrosis in rats

目的采用腺嘌呤诱导大鼠肾间质纤维化的模型,进一步了解苦参碱在肾小管-间质纤维化中的防治作用及其机制方法60只雄性大鼠随机分为3组:①正常对照组8只;②病理组28只;③治疗组24只按250 mg·kg-1·d-1给大鼠灌服腺嘌呤,连续21 d灌暇腺嘌呤1周后,治疗组每天还按20 mg·kg-1·d-1的剂量用苦参碱腹腔注射,分别观察治疗2,3,4周,3个不同时间点,正常对照、病理组和治疗组的血清肌酐、尿素氯、血清IL-6和肾小管间质的TGF-β1表达和肾组织病理改变等指标的变化,用放射免疫法检测血清IL-6的水平,免疫组化SABC法检测肾小管间质中的TGF-β1蛋白的表达和分布,采用HPIAS- 1000型全自动彩色图像分析系统,对免疫组化染色阳性信号进行扫描,半定量分析各组阳性表达面积百分比,肾组织HE染色丰定量分析各组肾小管-间质损伤指数结果苦参碱治疗组大鼠的血清肌酐、尿素氮与同期病理组比较,有明显的改善(P <0.05);血清IL-6水卓、肾小管间质的TGF-β1蛋白表达显著低于同期病理组(P<0.05),但均高于正常对照组(P<0.01) 苦参碱治疗的各组肾小管间质损伤指数低于病理组(P<0 05)。结论在腺嘌呤诱导的大鼠肾间质纤维化过程中,苦参碱能降低其血清BUN,Scr,IL-6水平和TGF-β1蛋白在肾小管间质中的表达,阻抑肾间质纤维化的进展,并有相应的时效关系。说明苦参碱对腺嘌呤导致肾间质纤维化大鼠模型的肾功能有一定保护作用,并可减轻肾间质纤维化的改变。

OBJECTIVE To study the mechanism relative to therapeutic effects of matrine on adenine-induced renal interstitial fibrosis in rats. METHODS Sixty male Wistar rats were selected and randomly divided into 3 groups. ① Eight rats were designed in normal control group; ②Tweenty-eight rats were designed in the pathological group; ③Twenty four rats were designed in the matrine group. Each rat in pathological group and matrine group was feed with adenine（250 mg·kg^- 1·d^- 1 ） orally for 21 d. After the treatment with adenine for one week, each rat in matrine group （20 mg·kg^- 1·d^- 1） in vehicle （1mL of 0.9% sodium chloride） was administered by intraperitoneal injection. Serum urea nitrogen, creatinine, IL-6 and to examine pathology of kidney in pathological group. Matrine group normal and control group were deter-mined after two weeks, three weeks and for weeks, respectively. Serum IL-6 was measured by radioimmunoassay. TGF-β1 expression in kidney was determined by immunohistochemical staining and semiquantitative analysis. Tubulointerstitial injury was evaluated by HE staining for semiquantitative analysis. RESULTS In matrine treated group, the renal function was superior to that in pathological group （ P 〈 0.05）, serum IL- 6 and renal TGF-β1 express level were obviously lower than that in pathological group （ P 〈 0.05） , but all these indexes were higher than that in normal control group （ P 〈 0.01 ）. In matrine group, the index of tubulointerstitial injury was lower than that in pathologal group （ P 〈 0.05）. CONCLUSION These data suggest that matrine inhibites the renal tubulointerstial fibrosis in adenine-induced rats model, which is involved in suppressing serum level of IL-6 and the expression of TGF-β1 in the tubulointerstitium.