瑞舒伐他汀对载脂蛋白E基因敲除小鼠动脉粥样硬化的治疗作用及其机制

发布时间：2018-12-24 15:11

【摘要】：目的:探讨瑞舒伐他汀对载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化模型血脂水平、动脉粥样硬化斑块及斑块内细胞凋亡的影响,阐明瑞舒伐他汀抑制动脉粥样斑块进展及斑块内细胞凋亡的机制。方法:选取健康6周龄雄性ApoE-/-小鼠30只,随机分为高脂饮食组、高脂+他汀组和普通饮食对照组,每组10只。前2组小鼠给予高脂饮食,普通饮食对照组小鼠给予普通饲料,喂养4周后,3组小鼠分别给予0.9%生理盐水、瑞舒伐他汀(10mg·kg~(-1)·d~(-1))和0.9%生理盐水灌胃8周,ELISA法检测各组小鼠血清血脂水平,HE染色观察小鼠动脉粥样硬化斑块大小,TUNEL法检测斑块内细胞凋亡,免疫组织化学染色法检测凋亡相关基因Bax蛋白表达。结果:高脂+他汀组小鼠血清总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平明显低于高脂饮食组(P0.05或P0.01),高脂+他汀组高密度脂蛋白胆固醇(HDL-C)水平明显高于高脂饮食组(P0.01)。高脂饮食组小鼠主动脉粥样斑块呈巨块型,斑块内可见大量泡沫细胞、胆固醇结晶、坏死细胞及炎性细胞;高脂+他汀组小鼠主动脉粥样斑块较小,泡沫细胞、坏死细胞和炎性细胞均较少;高脂+他汀组小鼠主动脉粥样斑块面积明显小于高脂饮食组(P0.01);高脂+他汀组小鼠主动脉粥样斑块内细胞凋亡指数明显低于高脂饮食组(P0.01)。与高脂饮食组比较,高脂+他汀组小鼠Bax蛋白表达明显降低。结论:瑞舒伐他汀可以抑制动脉粥样斑块进展,抑制斑块内细胞凋亡,其作用机制可能与线粒体途径有关。
[Abstract]:Aim: to investigate the effects of rosuvastatin on the levels of serum lipids and apoptosis in atherosclerotic plaque and plaque in ApoE-/- mice. To elucidate the mechanism of rosuvastatin inhibiting atherosclerotic plaque progression and apoptosis in plaque. Methods: 30 healthy male ApoE-/- mice aged 6 weeks were randomly divided into high fat diet group, high fat statins group and general diet control group with 10 rats in each group. The mice in the first two groups were given a high-fat diet, and the mice in the control group were given common diet. After 4 weeks of feeding, the three groups were given 0.9% normal saline, respectively. 10mg kg~ (-1) d ~ (-1) and 0.9% normal saline were perfused to stomach for 8 weeks. The serum lipid levels were measured by ELISA method and the size of atherosclerotic plaques in mice were observed by HE staining. Apoptosis in plaque was detected by TUNEL and the expression of apoptosis-related gene Bax was detected by immunohistochemical staining. Results: the levels of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in hyperlipidemic group were significantly lower than those in high fat diet group (P0.05 or P0.01). The level of high density lipoprotein cholesterol (HDL-C) in high fat statins group was significantly higher than that in high fat diet group (P 0. 01). The atherosclerotic plaques in the aorta of the high-fat diet group were of large size, and a large number of foam cells, cholesterol crystals, necrotic cells and inflammatory cells could be seen in the plaques. Atheromatous plaques were smaller, foam cells, necrotic cells and inflammatory cells were less in high-fat statins group than those in high-fat diet group (P0.01). Apoptosis index in aortic atherosclerotic plaque in high fat statins group was significantly lower than that in high fat diet group (P 0.01). Compared with the high fat diet group, the expression of Bax protein in the high fat statins group was significantly lower than that in the high fat diet group. Conclusion: rosuvastatin can inhibit the progression of atherosclerotic plaques and inhibit the apoptosis of cells in atherosclerotic plaques. The mechanism may be related to the mitochondrial pathway.
【作者单位】：吉林大学第二医院心血管内科;吉林省白山市通化矿业集团总医院心内科;内蒙古自治区兴安盟科右中旗高力板镇义和道卜卫生院;长春中医药大学附属医院心内科;
【基金】：国家中医药管理局国家中医临床研究基地业务建设科研专项基金资助课题(JDZX2012073)
【分类号】：R543.5

【相似文献】