辛伐他汀对慢性心力衰竭兔PTEN、β-catenin、p53的影响

发布时间：2018-06-20 18:34

本文选题：辛伐他汀 + 慢性心力衰竭　；参考：《新乡医学院》2017年硕士论文

【摘要】：背景慢性心力衰竭(chronic heart failure,CHF)是心血管疾病的最终转归,其防治成为近年的研究导向。辛伐他汀作为降脂药物,除降脂外还有抗炎、抑制凋亡、抑制心室重塑等作用,在慢性心力衰竭的治疗中有很大潜力,但其作用机制有待进一步探讨。目的研究辛伐他汀对慢性心力衰竭兔PTEN、β-catenin、p53的影响。方法 24只雄性新西兰大耳白兔,随机分为对照组、心衰模型组、辛伐他汀组,每组8只。心衰模型组、辛伐他汀组注射盐酸阿霉素(adriamycin,ADR)2mg·kg-1,每周1次,连续6周,第7周起注射盐酸阿霉素1.5mg·kg-1,连续6周,建立慢性心力衰竭兔模型;对照组给予相同容积的生理盐水。辛伐他汀组在首次注射盐酸阿霉素时给予辛伐他汀灌胃,剂量为1.5mg·kg-1·d-1,连续12周;对照组、心衰模型组给予相同容积的生理盐水灌胃12周。造模结束后通过心脏超声测量兔左心室结构和左室射血分数(left ventricular ejection fraction,LVEF)。处死兔并分离左室心肌,HE染色观察心肌细胞结构,免疫组织化学染色后检测PTEN、β-catenin、p53蛋白的阳性表达率,逆转录-聚合酶链反应(RT-PCR)检测PTEN m RNA、β-catenin m RNA、p53 m RNA的表达。结果 1.心功能检测结果显示:与对照组比较,心衰模型组、辛伐他汀组的左心室收缩末期内径(left ventricular end-systolic dimension,LVESD)、左心室舒张末期内径(left ventricular end-diastolic dimension,LVEDD)增大,LVEF下降,差异均具有统计学意义(P0.05);辛伐他汀组较心衰模型组LVESD、LVEDD减小,LVEF升高,差异均具有统计学意义(P0.05)。2.HE染色结果显示:对照组兔心肌细胞排列有序,呈束状,细胞核呈圆形,位于细胞中央,可见闰盘,心肌间质纤维组织较少;心衰模型组兔心肌细胞排列紊乱,可见细胞水肿,大部分出现心肌断裂,细胞间隙增宽,细胞核出现异型,闰盘消失,纤维组织增生;辛伐他汀组兔心肌细胞排列有序,细胞水肿、心肌断裂较心衰模型组减少,尚可见闫盘,心肌间质可见纤维组织增生。3.免疫组化检测各组标本心肌细胞中PTEN、β-catenin、p53蛋白表达显示:与对照组比较,心衰模型组、辛伐他汀组PTEN、β-catenin、p53蛋白阳性表达率均明显增高(P0.05),且辛伐他汀组PTEN、β-catenin、p53蛋白阳性表达率均低于心衰模型组(P0.05)。4.逆转录-聚合酶链反应(RT-PCR)检测各组标本心肌细胞中PTEN mRNA、β-catenin m RNA、p53 m RNA表达显示:心衰模型组、辛伐他汀组的PTEN m RNA、β-catenin m RNA、p53 m RNA相对表达量较对照组升高(P0.05);且辛伐他汀组PTEN m RNA、β-catenin m RNA、p53 m RNA相对表达量均低于心衰模型组(P0.05)。结论辛伐他汀可改善慢性心力衰竭兔心功能,抑制心肌细胞凋亡,可能与抑制PTEN、β-catenin、p53的表达有关。
[Abstract]:Background chronic heart failure is the ultimate outcome of cardiovascular disease, and its prevention and treatment has become the research direction in recent years. As a lipid lowering drug, simvastatin not only has anti-inflammatory, anti-apoptosis and anti-ventricular remodeling effects, but also has great potential in the treatment of chronic heart failure, but its mechanism needs further study. Objective to study the effect of simvastatin on PTEN, 尾-catenin p53 in rabbits with chronic heart failure. Methods Twenty-four male New Zealand white rabbits were randomly divided into control group, heart failure model group and simvastatin group. In the heart failure model group, simvastatin group was injected with adriamycin hydrochloride 2mg kg-1 once a week for 6 weeks, and adriamycin hydrochloride 1.5mg kg-1 was injected for 6 weeks from the 7th week to establish the model of chronic heart failure in rabbits, and the control group was given the same volume of normal saline. Simvastatin group was given simvastatin for 12 weeks at the dose of 1.5mg kg-1 d-1 at the first injection of adriamycin hydrochloride, while the control group was given the same volume of normal saline for 12 weeks. Left ventricular structure and left ventricular ejection fraction (LVEF) were measured by echocardiography. The myocardial structure was observed by HE staining in left ventricular myocardium. The positive rates of PTEN and 尾 -catenin p53 protein were detected by immunohistochemical staining. The expression of PTEN m RNA and 尾 -catenin m RNA-p53 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). Result 1. Compared with control group, left ventricular end-systolic dimension and left ventricular end-diastolic dimension (LVEDDD) of left ventricular end systolic diameter (LVEF) in simvastatin group were significantly increased, compared with control group. The differences were statistically significant (P 0.05), simvastatin group decreased LVEDD and LVEF increased compared with heart failure model group (P 0.05). 2. The results of HE staining showed that the cardiac myocytes of the control group were arranged in an orderly manner, with bundles and round nuclei. It is located in the center of the cell with intercalated disc and less interstitial fibrous tissue. In the heart failure model group, the cardiac myocytes are arranged disorderly, the cells are edema, most of them are myocardial rupture, the intercellular gap is widened, the nucleus is abnormal, the intercalated disc disappears. In simvastatin group, the arrangement of myocardial cells was orderly, cell edema, myocardial rupture was less than that in model group of heart failure, Yan Pan could be seen, and fibrous tissue proliferation could be seen in myocardial interstitial. 3. The expression of PTEN, 尾 -cateninine p53 protein in cardiac myocytes of each group was detected by immunohistochemistry: compared with the control group, the heart failure model group, The positive expression rates of PTEN, 尾 -cateninine p53 protein in simvastatin group were significantly higher than those in simvastatin group, and the positive expression rates of PTEN and 尾 -catenin p53 protein in simvastatin group were lower than those in heart failure model group. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect PTEN mRNAs and 尾 -catenin m RNA-p53 mRNA expression in cardiac myocytes of each group. The relative expression of PTEN m RNA, 尾 -catenin m RNA-p53 mRNA in simvastatin group was higher than that in control group, and the relative expression of PTEN m RNA, 尾 -catenin m RNA-p53 mRNA in simvastatin group was lower than that in heart failure model group (P 0.05). Conclusion Simvastatin can improve cardiac function and inhibit cardiomyocyte apoptosis in rabbits with chronic heart failure, which may be related to the inhibition of PTEN, 尾 -catenin p53 expression.
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.6

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