【作者】 刘爱东；

【导师】 潘贵书；

【作者基本信息】 遵义医学院 ， 生理学， 2012， 硕士

【摘要】 目的：在一定时间内连续给大鼠灌胃不同剂量的食用白酒,观察心脏结构、功能及检测心肌组织中ACE、ACE2及AngⅡ的变化。方法： SD大鼠124只按4wk、8wk、12wk三个时间点随机分成白酒组、酒精组、生理盐水组,每组分别又分为低、中和高剂量组,每组6只,共27组。按低剂量(0.25ml/100g/d)、中剂量(0.5ml/100g/d)、高剂量(1ml/100g/d),每日量分两次(每次按半量)给予大鼠灌胃,两次间隔时间超过9h以上。每周称体重一次,根据体重调整一周的灌胃量。分别在上述三个时间点测定左心室内压变化幅度(LVP),计算心脏／体重指数(HW/BW), Masson染色观察心肌纤维化,ELISA检测心肌组织AAngⅡ、ACE、ACE2含量,RT-PCR检测心肌细胞ACEmRNA和ACE2mRNA的表达。结果一：①4wk末白酒组的各剂量组左心室内压变化幅度、HW/BW与酒精组、生理盐水组比较无显著性差异(P>0.05)。②4wk末白酒组、酒精组的中、高剂量组的心肌细胞胞浆轻度浑浊、变性,纤维组织轻度增生,且以高剂量变化明显。③4wk末白酒组、酒精组的各剂量组的心肌组织AngⅡ、ACE、ACE2含量与生理盐水组比较,无显著性差异(P>0.05),但出现随剂量增加而升高的趋势。④4wk末白酒组、酒精组的各剂量组心肌组织ACEmRNA、ACE2mRNA的表达与生理盐水组比较,无明显变化(P>0.05)。结果二：①8wk末白酒组的各剂量组LVP、HW/BW与酒精组、生理盐水组比较无显著性差异(P>0.05)。②在8wk末,随着时间延长,从低剂量组到高剂量组的心肌细胞胞浆逐渐发生变性、浑浊,纤维组织逐渐增生明显,各剂量组中以酒精组变化明显。③8wk末白酒的中、高剂量组和酒精的中、高剂量组心肌组织AngⅡ、ACE含量分别高于生理盐水对照组、低剂量组(P<0.05,P<0.01),且酒精的高剂量组心肌组织ACE含量高于中剂量组(P<0.05)。④8wk末白酒和酒精的低、中、高剂量组心肌组织ACE2含量均高于生理盐水对照组(P<0.05,P<0.01,P<0.01),白酒和酒精的中剂量组、高剂量组和心肌组织ACE2含量分别高于各自的低剂量组(P<0.05,P<0.01),且高剂量组心肌组织ACE2还含量高于中剂量组(P<0.05)。⑤8wk末白酒和酒精中、高剂量组的心肌组ACE2mRNA、表达分别高于生理盐水对照组和低剂量组(p<0.05,p<0.01)。⑥8wk末白酒和酒精中、高剂量组的心肌组织ACEmRNA均高于生理盐水对照组(p<0.05,p<0.01)。白酒、酒精高剂量组的心肌组织ACEmRNA表达分别高于各自的低剂量组、中剂量组(p<0.01,p<0.05)。结果三：①12wk末白酒组、酒精组的各剂量组的LVP,HW/BW均比生理盐水组升高(P<0.05)。②在12wk末中,随着时间延长,从低剂量组到高剂量组的心肌细胞胞浆浑浊、变性逐步加重,纤维组织逐步明显增生,高剂量组还出现脂肪组织增生,各剂量组中以酒精组变化明显。③12wk末白酒组和酒精组的低、中、高剂量组心肌组织AngⅡ、ACE含量均高于生理盐水对照组(P<0.05,P<0.01,P<0.01),且中、高剂量组的AngⅡ、ACE含量均维持在高水平,高于低剂量组(P<0.01),而白酒高剂量组的心肌组织AngⅡ含量高于中剂量组(P<0.01)。④12wk末时白酒组和酒精组的低剂量组心肌组织ACE2含量明显高于生理盐水对照组(P<0.01),而中、高剂量组的ACE2含量均低于生理盐水对照组(P<0.01,P<0.01)。⑤12wk末白酒和酒精低剂量组的心肌组ACE2mRNA、ACE2表达均高于生理盐水对照组(p<0.01)。白酒和酒精中、高组的的心肌组织ACE2mRNA表达均低于生理盐水对照组(p<0.05)。⑥12wk末白酒和酒精低、中、高剂量组的心肌组织ACEmRNA表达分别高于生理盐水对照组(p<0.01)白酒和酒精的中、高剂量组的心肌组织ACEmRNA表达分别高于各自的低剂量组(p<0.05,p<0.01)。白酒和酒精高剂量组的ACEmRNA表达分别高于各自的中剂量组(p<0.05,p<0.05)结论：1.短期内少量饮酒对心肌功能无明显损伤,AngⅡ、ACE、ACE2含量无明显差异。2.长期饮酒可导致心肌纤维化,其变化程度与饮酒量以及时间长短有关。3.长期饮酒可破坏心肌内的ACE和ACE2平衡,使ACE和AngⅡ的升高,ACE2降低,导致心肌纤维化。4.在相同时间、相同剂量下,单纯酒精对心脏的损伤重于食用白酒。更多还原

【Abstract】 Objective:To pour various doses of alcohol into rats by gastric lavage within specified periods of time to observe their changes in the heart structure and function, detect the changes of ACE-. ACE2and AngⅡ in their myocardial tissue and explore the mechanism of alcohol damage to the heart.Methods:According to three different periods of time, namely,4W,8W and12W respec-tively,124SD rats were randomly divided into Saline Group, Alcohol Group, Liquor Group, each of which were further divided into low-dose group(0.25ml/100g/d), middle-dose group (0.5ml/100g/d) and high-dose group(lml/100g/d), a total of27groups. Rats were given liqu-or、alcohol and sline orally twice a day (each time half of their daily specified dose), respe-ctively, with an interval being more than9h. Their drinking amounts were adjusted in accor-dance with their weight weekly. Left ventricular pressure was determined, indexes of HW BW were calcul-ated. myocardial fibrosis was observed by Masson staining, Angll, ACE, ACE2content of myocardial tissue were detected by ELISA, ACEmRNA and ACE2mRNA expression by RT-PCR, ACE and ACE2expression by immunohistochemicals of myocar-dial cells.Results:①Compared with Saline Group, there were significant change(P<0.05) in left ventricular pressure and HW/BW index of both Liquor Group and Alcohol Group of any dose in12W.②The myocardial cell mildly went turbid and degenerated, and the fibrous tissue showed a mild tendency of hyperplasia in middle-dose group and high-dose group of Liquor Group and Alcohol Group in4W. With the dose increased and time prolonged, the myocardial cell gradually became turbid, degenerative and the fibrous tissue gradually became hyperplasia, there were obvious changes in alcohol groups of any dose in8W^12W. but hyperplasia worsened in the adipose tissue in high-dose groups in12W, there were obvious changes in alcohol groups of any dose.③The Angll and ACE contents of the myo- cardial tissue of both Liquor Group and Alcohol Group of middle and high doses are higher than the saline control group、low-dose groups(P<0.05, P<0.01) in8W, the AngⅡ and ACE contents maintained higher level in middle and high dose groups, but in the high-dose alcohol group, the Angll content was higher than that of the middle-dose alcohol group (P<0.05) in8W. Their in both Liquor Group and Alcohol Group of any dose were respec-tively higher than that of Saline Group in12W (P<0.05, P<0.01, P<0.01). Furthermore, the Angll and ACE contents maintained high level in both the middle and the high dose groups, higher than that of the low-dose group (P<0.05), but in Liquor Group of high-dose, the Angll content was higher than that of Liquor Group of middle-dose (P<0.05).④he ACE2contents in the myocardial tissue of Liquor Group and Alcohol Group of any dose were higher than that of Saline Group in8W (P<0.05, P<0.01, P<0.01), while the ACE2contents in both the middle-dose group and the high-dose group were higher than that of the low-dose group (P<0.05, P<0.01) and the ACE2content of the high-dose group was higher than that of the middle-dose dose(P<0.05).In12W, the ACE2contents of Liquor Group and Alcohol Group of low dose were significantly higher than that of Saline Group (P<0.01), while ACE2levels in Liquor Group and Alcohol Group of middle dose and high dose were respectively lower than that of Saline Groupand low dose in12W (P<0.01,P<0.01).⑤In the middle-dose group and the high-dose group of Liquor Group and Alcohol Group the ACE2mRNA expressions in the myocardial tissue were higher than that of Saline Group (P<0.05), higher than that of the low-dose group (P<0.Ol).In12W, the ACE2mRNA expre-ssion in low dose of Liquor Group and Alcohol Group were higher than that of Saline Group (P<0.01), while the ACE2mRNA expressions in both the middle-dose and the high-dose groups were respectively lower than that of Saline Group and low dose(P<0.05, P<0.01).⑥In the middle-dose group and the high-dose group, the ACEmRNA expressions in the myocardial tissue were respectively higher than that of Saline Group in8W(P<0.05, P<0.01). In the high-dose group, the ACEmRNA expressions were respectively higher than those of the middle-dose groups and the low-dose groups in8W (P<0.05, P<0.01). In12W, the ACEmRNA expressions in Liquor Group and Alcohol Group of any dose were respec-tively higher than that of Saline Group (P<0.05, P<0.01, P<0.01) while the ACEmRNA expressions in middle-dose groups and high-dose groups were respectively higher than those of low-dose groups (P<0.05, P<0,01) and in high-dose groups, the ACEmRNA expressions were higher than those of middle-dose groups (P<0.05).Conclusion:①small amount of alcohol consumption do not do apparent damage to the myocardial function in short term.②Long-term drinking can lead to myocardial fibrosis, whose degree is related to of the amount of alcohol consumption and drinking history.③Long-term alcohol consumption can damage the balance of cardiac ACE and ACE2, causing the increase of ACE and Angll and the decrease of ACE2, resulting in myocardial fibrosis.④Under the same conditions, pure alcohol is more obvious changes than alcohol consump-tion on the heart.更多还原