丹参酮ⅡA对ApoE基因敲除小鼠肝脏脂质沉积的影响及机制

The effect and mechanism of Tanshinone Ⅱ- A on hepatic lipid deposition in apoE^(-/-) mice

目的观察丹参酮ⅡA对ApoE基因敲除(ApoE-/-)小鼠肝脏脂质沉积及相关基因表达的影响,探讨丹参酮ⅡA抗AS作用及可能机制。方法 20只ApoE-/-小鼠随机分成模型组、丹参酮ⅡA组,10只C57BL/6J小鼠作为空白对照组。模型组、丹参酮ⅡA组给予高脂饲料喂养,空白对照组给予普通饲料。丹参酮ⅡA组每日灌胃丹参酮ⅡA(30 mg/kg)、模型组、空白对照组灌予等量生理盐水灌胃。全自动生化分析仪检测血清中TG、TC、HDL-C、LDL-C含量。HE和油红O染色观察小鼠肝脏组织结构变化以及脂质沉积情况,RT-PCR法检测肝脏低密度脂蛋白受体(LDL-R)、卵磷脂胆固醇脂酰转移酶(LCAT)基因mRNA水平,Western blotting法检测肝脏内LDL-R、LCAT蛋白表达。结果与空白对照组相比,模型组小鼠血清TC、TG、LDL-C水平显著升高,HDL-C水平显著降低,肝脏形成大量脂质沉积,肝脏LDL-R、LCAT基因mRNA和蛋白水平显著下调。与模型组相比,丹参酮ⅡA组小鼠TC、TG、LDL-C水平显著下降,HDL-C水平显著升高,肝脏脂质沉积明显减少,肝脏LDL-R、LCAT基因mRNA和蛋白水平显著上调。结论丹参酮ⅡA具有调节血脂和减少肝脏内脂质沉积的作用,其机制可能与调控LDL-R和LCAT基因表达相关。

Objective To observe effects of Tanshinone Ⅱ - A on hepatic lipid metabolism and related genes ex-pression in ApoE / mice so as to study its function and possible anti - atherosclerotic mechanism. Methods Twenty ApoE-/- mice were divided randomly into model group and Tanshinone Ⅱ -A group. Ten C57BL/6J mice with same age and genetic background were used as blank control group. Model group and Tanshinone Ⅱ - A group were fed with high fat diet, while blank control group was fed normal diet. Tanshinone Ⅱ - A group was given Tanshinone Ⅱ - A 30 mg/ kg by intragastric administration once a day for 8 weeks, the model group and blank control group were given normal saline. The contents of TG, TC, HDL - C, and LDL - C in serum were detected by automatic biochemical analyzer. The liver structure and lipid deposition were examined by HE and oil red staining method. The mRNA and protein of LDL - R and LCAT in liver were tested by RT - PCR and western blotting, respectively. Results Compared with blank control group, model group had significantly increa- ses in TC, TG, and LDL - C levels , decreases in HDL - C levels, and a large number of lipid deposit in liver. The liver LDL- R and LCAT mRNA and protein levels were decreased. Compared with model group, Tanshi-none 1I -A group had greatly decreased TC, TG, and LDL - C HDL- C concentration, and LDL- R, LCAT mRNA and protein has the beneficial effects of reducing the lipid deposition in liver. concentrations. Tanshinone Ⅱ- A increased levels in liver. Conclusion TanshinoneⅡ - A Its mechanism may possibly be related to LDL-R and LCAT gene expression.