摘要
目的观察阿伐他汀联合还原型谷胱甘肽对高血压大鼠肾损害的影响,并探讨其机制。方法将6周龄32只原发性高血压(SHR)大鼠分为联合组、阿伐他汀组、谷胱甘肽组、模型组各8只,以8只同周龄Wistar-Kyoto(WKY)大鼠为对照组。阿伐他汀组、谷胱甘肽组分别采用阿伐他汀20 mg/mL、还原型谷胱甘肽200 mg/(kg.d)灌胃,联合组两药合用。模型组及对照组大鼠以10 mL/kg蒸馏水每日灌胃。6周后检测各组大鼠肾脏组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)水平及过氧化物酶增殖物激活受体γ(PPARγ)、转化生长因子(TGF)-β1mRNA。结果与模型组相比,联合组、阿伐他汀组及谷胱甘肽组SOD活性明显升高,联合组最高(P均<0.05)。与模型组相比,联合组、阿伐他汀组及谷胱甘肽组MDA水平明显减少,联合组最低(P均<0.05)。联合组PPARγmRNA表达量高于其他各组、TGF-β1 mRNA表达量低于对照组外的其他各组(P均<0.05)。结论阿伐他汀联合还原型谷胱甘肽干预治疗能有效抑制SHR大鼠高血压对其肾脏的损害作用,较单独用药效果显著,可能是通过上调PPARγmRNA表达、下调TGF-β1 mRNA表达来实现的。
Objective To observe effect of atorvastatin combined with reduced glutathione on renal damage in hyper- tensive rats and explore its mechanism. Methods 32 SHR rats with 6 week old were divided into combined group, atorvastatin group, glutathiene group, model group of g each, with g of the same age Wistar-Kyoto （WKY） rats served as con- trol group. Atorvastatin group, glutathione group was treated with atorvastatin 20 mg/mL, reduced glutathione 200 mg/（ kg . d） gastric perfusion, respectively, combined group was treated with both two drugs. Rats in control group and model group daily by gavage for 10 mL/kg of distilled water gastric perfusion. After 6 weeks, SOD avtivity, MDA levels and PPARγ , TGF-β1 mRNA in rat kidney were checked. Results Compared with model group, SOD activity of combined group, atorvastatin group and glutathione group were significantly elevated, and combined group was the highest （ all P 〈 0.05 ）. Compared with model group, MDA levels of combined group, atorvastatin group and glutathione group were signifi- cantly reduced, the combined group was the lowest （ all P 〈 0.05 ）. Expression of PPAR5, mRNA in combined group was higher than other groups, expression of TGF- β1 mRNA was lower than the other groups （ all P 〈 0.05 ）. Conclusions Atorvastatin combined with reduced glutathione intervention therapy can inhibit hypertension on renal function in SHR rat, the effect is remarkable compared with drug treated alone. The mechanisms may be increasing expression of PPARγ mRNA and reducing expression of TGF-β1 mRNA.
出处
《山东医药》
CAS
2012年第30期13-15,共3页
Shandong Medical Journal
基金
中国药学发展奖励工作委员会北京长江药学发展基金会资助项目(L2011210)
