脱氢洛伐他汀的调脂和抗炎作用的关系

Relationship between lipidemia-modulating and anti-inflammatory effects of dehydrolovastatin

目的:观察洛伐他汀的衍生物脱氢洛伐他汀(dehydrolovastatin)调脂和抗炎作用的关系。方法:以洛伐他汀作为阳性对照药,用高脂饲料喂养建立高脂血症大鼠模型,灌胃给予不同剂量的脱氢洛伐他汀,第12周末全自动生化分析仪测定血脂水平,获取肝脏组织进行病理切片以观察肝脏脂肪变性情况。采用二甲苯致小鼠耳肿胀模型和采用棉球植入小鼠背部致肉芽肿模型,观察洛伐他汀和脱氢洛伐他汀的抗炎作用。结果:脱氢洛伐他汀能明显降低高血脂大鼠血清总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平,并能阻止脂肪肝样变性,其作用似弱于等剂量的洛伐他汀。脱氢洛伐他汀对二甲苯所致耳急性炎症反应和棉球植入致肉芽肿形成的慢性炎症均有显著抑制作用,其作用与洛伐他汀相当。结论:脱氢洛伐他汀的良性调脂作用似弱于洛伐他汀,但其抑制急性和慢性炎症反应的作用与洛伐他汀相当,提示他汀类的调脂和抗炎作用并不平行。

Objective： To investigate the effects of dehydrolovastatin on blood lipids in rats and inflammatory reactions in mice.Methods： Hyperlipidemia in rats was induced by feeding high fat diet and the rats were treated with dehydrolovastatin,ig,once a day for 12 weeks.Blood lipid levels were determined with automatic biochemistry analyzer after treatment.The pathomorphology of hepatic tissues was evaluated by microscopy after HE staining.The anti-inflammatory effect of dehydrolovastatin was evaluated in xylene-induced ear skin inflammation and cotton ball implantation-induced granuloma in mice.Results： Dehydrolovastatin not only decreased serum TC and LDL-C levels but also blunted development of fatty liver caused by high fat diet,even though these effects were less than that of lovastatin.However,dehydrolovastatin showed an anti-inflammatory effect similar to lovastatin in both inflammation models.Conclusion： Dehydrolovastatin and lovastatin have equivalently inhibiting effects on acute and chronic inflammatory reactions,but the lipidemia-modulating effect of dehydrolovastatin is less than that of lovastatin.