本文選題：辛伐他汀 + 慢性心力衰竭�。� 參考：《新鄉(xiāng)醫(yī)學(xué)院》2017年碩士論文

【摘要】：背景 慢性心力衰竭(chronic heart failure,CHF)是心血管疾病的最終轉(zhuǎn)歸,其防治成為近年的研究導(dǎo)向。辛伐他汀作為降脂藥物,除降脂外還有抗炎、抑制凋亡、抑制心室重塑等作用,在慢性心力衰竭的治療中有很大潛力,但其作用機(jī)制有待進(jìn)一步探討。目的 研究辛伐他汀對慢性心力衰竭兔PTEN、β-catenin、p53的影響。方法 24只雄性新西蘭大耳白兔,隨機(jī)分為對照組、心衰模型組、辛伐他汀組,每組8只。心衰模型組、辛伐他汀組注射鹽酸阿霉素(adriamycin,ADR)2mg·kg-1,每周1次,連續(xù)6周,第7周起注射鹽酸阿霉素1.5mg·kg-1,連續(xù)6周,建立慢性心力衰竭兔模型;對照組給予相同容積的生理鹽水。辛伐他汀組在首次注射鹽酸阿霉素時給予辛伐他汀灌胃,劑量為1.5mg·kg-1·d-1,連續(xù)12周;對照組、心衰模型組給予相同容積的生理鹽水灌胃12周。造模結(jié)束后通過心臟超聲測量兔左心室結(jié)構(gòu)和左室射血分?jǐn)?shù)(left ventricular ejection fraction,LVEF)。處死兔并分離左室心肌,HE染色觀察心肌細(xì)胞結(jié)構(gòu),免疫組織化學(xué)染色后檢測PTEN、β-catenin、p53蛋白的陽性表達(dá)率,逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(RT-PCR)檢測PTEN m RNA、β-catenin m RNA、p53 m RNA的表達(dá)。結(jié)果 1.心功能檢測結(jié)果顯示:與對照組比較,心衰模型組、辛伐他汀組的左心室收縮末期內(nèi)徑(left ventricular end-systolic dimension,LVESD)、左心室舒張末期內(nèi)徑(left ventricular end-diastolic dimension,LVEDD)增大,LVEF下降,差異均具有統(tǒng)計學(xué)意義(P0.05);辛伐他汀組較心衰模型組LVESD、LVEDD減小,LVEF升高,差異均具有統(tǒng)計學(xué)意義(P0.05)。2.HE染色結(jié)果顯示:對照組兔心肌細(xì)胞排列有序,呈束狀,細(xì)胞核呈圓形,位于細(xì)胞中央,可見閏盤,心肌間質(zhì)纖維組織較少;心衰模型組兔心肌細(xì)胞排列紊亂,可見細(xì)胞水腫,大部分出現(xiàn)心肌斷裂,細(xì)胞間隙增寬,細(xì)胞核出現(xiàn)異型,閏盤消失,纖維組織增生;辛伐他汀組兔心肌細(xì)胞排列有序,細(xì)胞水腫、心肌斷裂較心衰模型組減少,尚可見閆盤,心肌間質(zhì)可見纖維組織增生。3.免疫組化檢測各組標(biāo)本心肌細(xì)胞中PTEN、β-catenin、p53蛋白表達(dá)顯示:與對照組比較,心衰模型組、辛伐他汀組PTEN、β-catenin、p53蛋白陽性表達(dá)率均明顯增高(P0.05),且辛伐他汀組PTEN、β-catenin、p53蛋白陽性表達(dá)率均低于心衰模型組(P0.05)。4.逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(RT-PCR)檢測各組標(biāo)本心肌細(xì)胞中PTEN mRNA、β-catenin m RNA、p53 m RNA表達(dá)顯示:心衰模型組、辛伐他汀組的PTEN m RNA、β-catenin m RNA、p53 m RNA相對表達(dá)量較對照組升高(P0.05);且辛伐他汀組PTEN m RNA、β-catenin m RNA、p53 m RNA相對表達(dá)量均低于心衰模型組(P0.05)。結(jié)論 辛伐他汀可改善慢性心力衰竭兔心功能,抑制心肌細(xì)胞凋亡,可能與抑制PTEN、β-catenin、p53的表達(dá)有關(guān)。
[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.
【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R541.6

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