缬草油对高胆固醇血症大鼠肾间质纤维化的改善作用及机制探讨

Therapeutic effectiveness of valerian oil in the treatment of renal tubulointerstitial fibrosis in hypercholesterolemic rats

目的观察缬草油对高胆固醇血症大鼠肾间质纤维化的改善作用并探讨其可能机制。方法将64只SD大鼠随机分为正常组、高脂组、缬草油组和辛伐他汀组，每组16只。缬草油组给予缬草油25mg·kg^-1·d^-1灌胃，辛伐他汀组同时给予辛伐他汀5mg·kg^-1·d^-1灌胃。比较各组大鼠总胆固醇（TC）、甘油三酯、低密度脂蛋白（LDL）、高密度脂蛋白、24h尿蛋白量、血肌酐（SCr）、肾间质损伤指数及转化生长因子β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）mRNA和蛋白表达。结果与高脂组相比，第16周时缬草油组肾小管间质损伤指数降低，TC、LDL、24h尿蛋白量和SCr降低，差异均有统计学意义（P〈0．01）。与正常组相比，第8周时，高脂组肾小管内TGF-β1表达增多，差异有统计学意义（P〈0．01），而α-SMA表达未见明显升高；第16周时，TGF-β1表达更为明显，α—SMA表达明显增加，差异均有统计学意义（P〈0．01）。缬草油能显著降低各时间点TGF-β1、rSMA蛋白和mRNA表达，其改善作用较辛伐他汀更明显。结论缬草油可改善高脂血症大鼠肾间质纤维化，可能与其调节血脂，下调肾组织TGF-β1表达，抑制肾小管上皮细胞转分化有关。

Objective To evaluate the protective effects of valerian oil on renal tuhulointerstitial fibrosis in hypercholesterolemie rats, and study its possible mechanisms. Methods SD rats were randomly divided into control group, hyperlipidemia group, valerian oil （25 mg·kg^-1 ·d^- 1 for lavage） group, and simvastatin group （5 mg·kg^- 1 ·d^-1 for lavage）. Serum total eholesterol（TC）, tfiglyeefide, low density lipoprotein（LDL）, high density lipoprotein, 24 hour urinary albumin, serum ereatinine（SCr）, renal tubulointerstitial injury indexes were assessed, and the mRNA and protein expression of transforming growth factor-β1 （TGF-β1） and α-smooth muscle actin（α-SMA） were detected at the same time. Results The renal tubulointerstitial injury indexes in hyperlipidemia group were obviously improved by valerian oil, accompanied with decreased TC,LDL,24 hour urine protein and SCr（P〈0. 01）. As compared with control group, the protein and mRNA expression levels of TGF-β1 were increased in hyperlipidemia group（P〈0. 01 ）, but the expression level of α-SMA showed no significant difference between control group and hyperlipidemia group at the 8th week. The protein and mRNA expression levels of TGF-β1 were increased more significantly at the 16th week, accompanied with an increased expression of α-SMA（P〈0. 01 ）. Valerian oil could significantly decrease the protein and mRNA expression levels of TGF-β1 and α-SMA at each time points, and the effect was better than in simvastatin group. Conclusions Valerian oil can improve renal tubulointerstitial fibrosis through decreasing serum lipid, dowrvregulating the TGF-β1 expression, and inhibiting trans- differentiation of renal tubular epithelial cells.