马兜铃酸致大鼠肾小管损伤及对肾组织骨形态发生蛋白7 mRNA表达.docVIP

马兜铃酸致大鼠肾小管损伤及对肾组织骨形态发生蛋白7 mRNA表达 　【摘要】 　　目的：观察关木通成分马兜铃酸（aristolochic acid, AA）引起的大鼠肾小管损伤，及肾组织骨形成蛋白7（bone morphogenetic protein7, BMP7）mRNA表达水平的变化，探讨马兜铃酸肾病的发病机制。 　　方法：46只Wistar大鼠随机分为正常对照组20只和AA组26只。AA组按AA 20 mg/(kg·d)灌胃关木通浸膏，正常对照组等容量饮用水灌胃。于第4、8和12周末用代谢笼分别留取24 h尿液，检测尿N乙酰βD氨基葡萄糖苷酶（NacetylβDglucosaminidase, NAG）活性；腹主动脉取血检测血清肌酐（serum creatinine, SCr）含量；观察肾组织病理的改变及肾小管损伤程度；免疫组化检测肾小管增殖细胞核抗原（proliferating cell nuclear antigen, PCNA）表达；半定量逆转录聚合酶链式反应法检测肾组织BMP7 mRNA的表达。 　　结果：与正常对照组比较，用药4、8和12周后AA组大鼠尿NAG活性增加，差异有统计学意义（Plt;0.05，Plt;0.01），SCr/体质量比值升高（Plt;0.01）。肾脏病理表现为肾小管浊肿、变性和脱落等急性小管间质损伤，随着用药时间延长，肾小管损伤程度进行性加重；AA组大鼠肾小管PCNA增殖指数在用药4周和8周后显著升高（Plt;0.01），12周后有所下降（Plt;0.05）；用药4周后，AA组大鼠肾组织BMP7 mRNA表达低于对照组（Plt;0.05），并随着用药时间延长减少更明显（Plt;0.01）。 　　结论：AA可引起大鼠肾小管损伤，使肾小管再生修复能力下降，抑制BMP7 mRNA表达。这可能是马兜铃酸肾病发生发展的机制之一。 【关键词】 马兜铃酸; 肾小管; 关木通; 骨形态发生蛋白7; 大鼠 　　Objective: To investigate the pathogenic mechanism of aristolochic acid nephropathy (AAN) by observing the renal tubular injury and the change of the expression of bone morphogenetic protein7 (BMP7) mRNA in renal tissue of rats induced by aristolochic acid (AA), an active constituent in Caulis Aristolochiae Manshuriensis (CAM). 　　Methods: Fortysix male Wistar rats were randomly divided into normal control group (n=20) and AAtreated group (n=26). Rats in AAtreated group were intragastrically administered with AA 20 mg/(kg·d), and rats in control group were treated with equal volume of potable water. At the end of the 4th, 8th and 12th week of administration, the 24 hurine was collected by metabolic cage for detecting the activity of NacetylβDglucosaminidase (NAG) and the blood samples were obtained from abdominal aorta for detecting serum creatinine (SCr). Pathological change and the degree of injury of the kidneys were observed by microscopy. The expression of proliferative cell nuclear antigen (PCNA) was detected by immunohistochemical method, and mRNA expression of bone morphogenetic protein7 (BMP7) in the renal tissue was d