泽泻醇提物长期喂养大鼠,探究其对大鼠的肾毒性作用,并研究其肾毒性的可能的分子机制。60只雌性大鼠随机分为空白组,雷公藤对照组,庆大霉素对照组,泽泻高、中、低剂量组,连续给药6个月。利用高效液相色谱仪(HPLC)对泽泻提取物成分进行分析,同时采用HE染色检测肾脏病理变化,通过Western blot法、免疫组织化学和q-PCR法检测Kim-1,clusterin,LCN2,osteopontin,ceruloplasmin和TIMP1蛋白和m RNA水平。HPLC解析出泽泻醇提物中的8个成分(环氧泽泻烯,泽泻醇F,泽泻醇A,24-乙酰泽泻醇F,泽泻醇A-24-醋酸酯,泽泻醇B,23-乙酰泽泻醇B和23-乙酰泽泻醇C)。HE染色结果显示,高、中剂量的大鼠肾脏间质炎性细胞浸润,肾小管上皮细胞水肿且形态发生变化。与空白组相比,雷公藤和庆大霉素对照组大鼠肾脏Kim-1,clusterin,LCN2,osteopontin和TIMP1蛋白和m RNA水平显著地提高,而ceruloplasmin蛋白和m RNA水平显著地降低;给予泽泻高、中剂量6个月后,大鼠肾脏Kim-1,clusterin,LCN2,osteopontin和TIMP1蛋白和m RNA水平也有显著地提高,而ceruloplasmin蛋白和m RNA水平显著地降低。长期大剂量服用泽泻醇提物可导致雌性大鼠产生肾毒性,其分子机制可能是通过调节Kim-1,ceruloplasmin,clusterin,LCN2,osteopontin和TIMP1等蛋白的表达来实现。 Alisma alcohol extract long-term feeding rats to explore its nephrotoxic effect on rats and to study the possible molecular mechanism of nephrotoxicity. 60 female rats were randomly divided into blank group, tripterygium control group, gentamicin control group, Alisma high, medium and low dose groups, continuous administration for 6 months. The constituents of Alisma orientalis extract were analyzed by high performance liquid chromatography (HPLC), and the pathological changes of kidney were detected by HE staining. The expressions of Kim-1, clusterin, LCN2, osteopontin were detected by Western blot, immunohistochemistry and q- , ceruloplasmin and TIMP1 protein and m RNA levels. Eight components in the extract of Alisma orientalis were analyzed by HPLC (Epoxy-Alizarin, Alisol F, Alisol A, 24-Alisalcohol F, Alisma A-24-Acetate, Alcohol B, 23-Acetylsalcohol B and 23-Acetylsalcohol C). HE staining showed that high and medium dose of rat interstitial inflammatory cell infiltration, tubular epithelial cell edema and morphological changes. Compared with the blank group, the protein and mRNA levels of Kim-1, clusterin, LCN2, osteopontin and TIMP1 in the kidney of tripterygium wilfordii and gentamicin control groups were significantly increased, while the levels of ceruloplasmin protein and m RNA were significantly reduced; After six months of high and medium dose, the levels of Kim-1, clusterin, LCN2, osteopontin and TIMP1 protein and mRNA in rat kidney were significantly increased, while the levels of ceruloplasmin protein and m RNA were significantly decreased. Long-term high-dose administration of Alisma orientalis alcoholic extract can cause nephrotoxicity in female rats. The molecular mechanism may be through the regulation of the expressions of Kim-1, ceruloplasmin, clusterin, LCN2, osteopontin and TIMP1.