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化瘀祛痰方通过调节ApoE^(-/-)小鼠胆固醇代谢相关基因表达抗动脉粥样硬化 被引量:33

Effect of Huayuqutan Recipe on Atherosclerosis by Regulating the Expression of Cholesterol Metabolism Related Genes in Apolipoprotein E Gene Knockout Mice
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摘要 目的观察化瘀祛痰方对载脂蛋白E基因敲除(ApoE-/-)小鼠粥样斑块以及胆固醇代谢相关基因的影响,探讨化瘀祛痰方抗动脉粥样硬化(As)作用及可能的机制。方法 10只C57BL/6/J小鼠作为空白对照组,30只ApoE-/-小鼠随机分为模型组、化瘀祛痰组[20 g/(kg·d)]和辛伐他汀组[0.005 g/(kg·d)]。全自动生化分析仪检测血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDLC),HE染色观察主动脉结构及动脉粥样硬化程度,油红O染色观察主动脉脂质沉积,RT-PCR和Western blot检测肝脏低密度脂蛋白受体(LDLR)、卵磷脂胆固醇酰基转移酶(LCAT)及主动脉CD36 mRNA和蛋白表达水平,流式细胞术检测腹腔巨噬细胞CD36蛋白表达。结果与空白对照组相比,模型组小鼠血清TC、TG、LDLC水平显著升高;HDLC水平显著降低,主动脉管腔中形成较大粥样斑块,管壁形成大量脂质沉积,肝脏LDLR、LCAT基因表达显著下调,主动脉、巨噬细胞CD36基因表达显著上调。通过药物干预,与模型组相比,化瘀祛痰组和辛伐他汀组小鼠TC、TG、LDLC水平显著下降,HDLC显著升高,主动脉管腔中粥样斑块面积和管壁脂质沉积量明显减少,肝脏LDLR、LCAT基因表达显著上调,主动脉、巨噬细胞CD36基因表达显著下调。结论化瘀祛痰方可抑制ApoE-/-小鼠主动脉斑块形成,其机制可能与调控血脂及胆固醇代谢相关基因LDLR、LCAT及CD36的表达有关。 Aim To observe the influence of Huayuqutan recipe on the metabolism of cholesterol in apolipopro- tein E gene knockout (ApoE-/- ) mice, so as to illuminate the role and mechanism of Huayuqutan recipe on atherosclero- sis. Methods Ten C57BL/6/J mce were used as blank group. Thirty ApoE -/- mice were randomly divided into model group, Huayuqutan recipe group and simvastatin group. The levels of serum lipid were tested by biochemical meth- ods. HE and oil red staining method were used to observe the aortic wall injury of ApoE -/- mice atherosclerotic mice. RT-PCR and Western blot methods were used to test the changes of expression of low-density lipoprotein receptor (LDLR), lecithin-cholesterol acyl transferase (LCAT) in liver and CD36 in aortic wall. The expression of CD36 in macrophages was detected by flow cytometer. Results Compared with the blank group, the serum tfiglyceride (TG), total choles terol (TC) and low-density lipoprotein cholesterol (LDLC) levels and the expression of CD36 in aortic wall and macropha ges were significantly increased while high-density lipoprotein cholesterol (HDLC) level and expression of LDLR, LCAT in liver were significantly decreased in the model group. In Huayuqutan recipe group and simvastatin group, the serum content of TG, TC and LDLC were lower and HDLC was higher compared with the model group. At the same time, the ex pression of LDLR, LCAT in liver were up-regulated and CD36 in aortic wall as well as macrophages was obviously down regulated. Conclusion Huayuqutan recipe could inhibit the formation of the atherosclerotic plaques, which might be related to the regulation of blood lipid, the expression of LDLR, LCAT as well as CD36.
出处 《中国动脉硬化杂志》 CAS CSCD 北大核心 2014年第1期1-6,共6页 Chinese Journal of Arteriosclerosis
基金 国家自然科学青年基金项目(81202834) 沈阳市科技局计划项目(F12-277-1-49) 辽宁省高等学校杰出青年学者成长计划资助项目(LJQ2011100) 中国博士后科学基金特别资助项目(201104611)
关键词 化瘀祛痰方 动脉粥样硬化 载脂蛋白E基因敲除小鼠 低密度脂蛋白受体 胆固醇 Huayuqutan Recipe Atherosclerosis Apolipoprotein E Gene Knockout Mice Low Density Lipo-protein Receptor Cholesterol
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