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目的为探讨苦参碱对腺嘌呤诱导大鼠肾小管-间质纤维化的防治作用及其机制。方法60只雄性Wistar大鼠被随机分为3组①正常对照组(NCG)8只;②腺嘌呤处理组(ATG)28只;③苦参碱治疗组(MTG)24只。按250mg·kg-·1d-1体重给ATG和MTG的大鼠灌服腺嘌呤,连续21天,而灌服腺嘌呤1周后,MTG的大鼠每天还按20mg·kg-·1d-1的剂量用苦参碱腹腔注射,分别观察苦参碱治疗的大鼠在14天、21天和28天的血清尿素氮、肌酐、IL-6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,免疫组化法检测肾组织TGF-β1蛋白的表达,并对免疫组化染色阳性信号进行半定量分析,用HE染色对各组肾小管-间质损伤进行半定量分析。结果在相同时间点上,MTG大鼠的血清肌酐、尿素氮与ATG大鼠比较,有明显的改善(P<0.05);MTG大鼠的血清IL-6水平、肾小管间质的TGF-β1蛋白表达显著低于ATG大鼠(P<0.05),但均高于NCG大鼠(P<0.01),MTG的大鼠肾小管间质损伤指数低于ATG大鼠(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。
Objective To investigate the preventive and therapeutic effects of matrine on adenine-induced tubulointerstitial fibrosis in rats. Methods Sixty male Wistar rats were randomly divided into 3 groups: 1 normal control group (NCG), 2 adenine-treated group (ATG), and 3 matrine-treated group (MTG). Adenine was intragastrically administered to rats with ATG and MTG at a dose of 250 mg·kg -1 d-1 for 21 consecutive days. After 1 week of adenine, MTG rats were treated with 20 mg·kg -1 d -1 per day. The doses were intraperitoneally injected with matrine, and the changes of indexes such as serum urea nitrogen, creatinine, IL-6, and renal pathological changes at 14 days, 21 days, and 28 days were observed in matrine-treated rats. The levels of serum IL-6 were detected by immunohistochemistry. The expression of TGF-β1 protein was detected by immunohistochemistry. Semi-quantitative analysis of immunohistochemically positive signals was performed. HE staining was used to treat each group of tubulointerstitial injury in half. Quantitative analysis. Results At the same time point, serum creatinine and urea nitrogen in MTG rats were significantly improved compared with ATG rats (P<0.05); serum IL-6 levels in MTG rats and TGF-β1 in tubulointerstitium were significantly improved. The protein expression was significantly lower than that of ATG rats (P<0.05), but higher than that of NCG rats (P<0.01). The renal tubulointerstitial injury index of MTG rats was lower than that of ATG rats (P<0.05). Conclusion In the course of adenine-induced renal interstitial fibrosis in rats, matrine can reduce the levels of serum BUN, Scr, IL-6 and the expression of TGF-β1 protein in tubulointerstitium, and inhibit renal interstitium. The progress of fibrosis.