Objective To investigate the effect of miR-155 gene knockout on the formation of atherosclerosis in rats and the effect of simvastatin on atherosclerosis in rats. Methods 20 male SD rats with miR-155 knockout were used as experimental group. Vitamin D3 was injected intraperitoneally and fed with high fat diet to rats. After the model was completed, the experimental group was randomly divided into two groups: experimental modeling group and experimental treatment group, each group has 10 rats. The rats in the experimental treatment group were given a certain dose of simvastatin . The experimental modeling group was given the same amount of saline.20 healthy male SD rats were randomly divided into normal control group and normal treatment group. 10 rats in each group, Normal treatment group was injected with the same amount of normal saline and fed as same as experimental treatment group. Normal control group was given the same amount of saline. HE staining was used to observe the damage of aorta in four groups; The serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL) were measured; QRT-PCR was used to detect the expression of vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 (IL-6), monocyte chemoattractant protein- 1 (MCP-1) mRNA expression in different groups. Results Compared with the normal control group, the aorta of the model group showed typical AS plaque formation. Compared with the normal control group, the levels of TC, TG and LDLC in the experimental model group, experimental treatment group and normal treatment group were significantly higher than those in the normal model group, the difference was statistically significant (P<0.05). Compared with the experimental model group, the levels of TC, TG and LDLC in the normal treatment group were significantly lower (P<0.05). Compared with the normal treatment group, the levels of TC, TG and LDLC in experimental treatment group were significantly decreased and the level of HDLC was significantly increased (P<0.05). Compared with the normal control group, the mRNA expression levels of VCAM-1, IL-6 and MCP-1 in the experimental model group,experimental treatment group and normal treatment group were significantly higher than those in the normal control group (P<0.05). Compared with the experimental model group, the expression of VCAM-1, IL-6 and MCP-1 mRNA in the normal treatment group was significantly lower(P<0.05). Compared with the normal treatment group, the mRNA expression levels of VCAM-1, IL-6 and MCP-1 in experimental treatment group were significantly lower (P<0.05). Conclusion MiR-155 gene knockout can prevent the formation of atherosclerosis in rats, and the beneficial effect of simvastatin on the treatment of atherosclerosis in rats may provide a direction for the prevention and treatment of atherosclerosis.%目的 探讨miR-155基因敲除对大鼠动脉粥样硬化形成及对辛伐他汀治疗大鼠动脉粥样硬化疗效的影响.方法 miR-155基因敲除雄性SD大鼠20只作为实验组,腹腔注射维生素D3,高脂饲料喂养进行大鼠动脉粥样硬化建模.8周后将实验组大鼠按完全随机抽样方法分为实验模型组和实验治疗组,每组10只,实验治疗组大鼠给予10 mg/kg辛伐他汀,实验模型组给予等量生理盐水.另取相同遗传背景、鼠龄和体重的雄性SD大鼠20只作为正常组,随机分为正常对照组和正常治疗组,每组10只,正常治疗组予以和实验治疗组大鼠同样的建模和给药,正常对照组普通饲料喂养,腹腔注射等量生理盐水.HE染色观察4组大鼠主动脉损伤;检测各组大鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)和高密度脂蛋(HDL);qRT-PCR检测血管细胞粘附分子-1(VCAM-1)、白介素6(IL-6)、单核细胞趋化蛋白-1(MCP-1)mRNA在不同组别表达情况.结果 与正常对照组相比,各模型组主动脉均见AS斑块形成.与正常对照组相比,正常模型组、实验模型组和辛伐他汀组大鼠TC、TG、LDLC水平均明显升高,正常模型组HDL明显下降,差异有统计学意义(P<0.05).与正常模型组比较,实验模型组大鼠TC、TG、LDL水明显降低,HDL明显升高,差异有统计学意义(P<0.05).与实验模型组相比,辛伐他汀组大鼠TC、TG、LDL均明显降低,HDL明显升高,差异有统计学意义(P<0.05).与正常对照组相比,正常模型组、实验模型组和辛伐他汀组大鼠VCAM-1、IL-6和MCP-1的mRNA相对表达升高,差异有统计学意义(P<0.05).与正常模型组比较,实验模型组大鼠VCAM-1、IL-6和MCP-1的mRNA表达降低,差异有统计学意义(P<0.05).与实验模型组相比,辛伐他汀组大鼠VCAM-1、IL-6和MCP-1的mRNA表达降低,差异有统计学意义(P<0.05).结论 miR-155基因敲除可预防大鼠动脉粥样硬化形成,对辛伐他汀治疗大鼠动脉粥样硬化疗效产生有利的影响,可能为预防及治疗动脉粥样硬化提供方向.
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