阿托伐他汀对压力负荷性心肌肥厚的保护作用及其机制的研究
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摘要
[目的]心肌肥厚可继发于多种心血管疾病,是心血管疾病死亡率的独立的危险因素,因此防治心肌肥厚具有重要的临床意义和社会意义。本实验旨在观察阿托伐他汀对压力负荷造成的心肌肥厚的影响,并探讨其可能的机制。
[方法]40只wistar大鼠,随机分为心肌肥厚组(n=20),假手术组(n=10),空白对照组(n=10)。心肌肥厚组以缩窄腹主动脉的方法造成后负荷增大,从而引起心肌肥厚,假手术组采用相同的手术方法,但只分离腹主动脉,但不结扎,空白对照组不予处理。术后1周测量血压以确定造模是否成功。确认造模成功后心肌肥厚组再随机分为心肌肥厚对照组(n=10)及心肌肥厚药物组(n=10)。心肌肥厚药物组通过灌胃的方式给予阿托伐他汀2mg/kg·d,至术后8周,同时心肌肥厚组、假手术组及空白对照组给予等量的生理盐水灌胃。8周后处死大鼠,测量其心脏重量/体重、左心室重量/体重的比值,以及病理切片的左室壁厚度、心肌细胞直径,并通过逆转录PCR(RT-PCR)的方法测定心肌组织中心调理素(CT-1)和白细胞介素18(IL-18)的表达情况。
[结果]术后两周心肌肥厚组的血压较术前明显升高(P＜0.05),较假手术组及空白对照组也明显升高(p＜0.05)。与空白对照组比较心肌肥厚组的心脏重量/体重、左心室重量/体重、左室壁厚度和心肌细胞直径均明显增大(P＜0.05),CT-1及IL-18mRNA表达也明显升高(P＜0.05),而心肌肥厚药物组上述各项指标均较心肌肥厚对照组明显减少,而与空白对照组无差别(P≥0.05)。
[结论]阿托伐他汀可以防治压力负荷增大造成的心肌肥厚,并且伴随有炎症因子水平的降低,说明阿托伐他汀的这种作用可能与其抗炎作用有关。
Objective Myocardial hypertrophy which can be caused by many heart diseases is a independent risk factor of the motality of cardiovascular disease.The purpose of this study is to observe the effect of atorvastatin on the myocardial hypertrophy caused by pressure overload and to find out the possible mechanisms.
Method 40 wistar rats were randomized into myocardial hypertrophy group,drug group, fake operation group and control group.Pressure overload was achieved by surgical constricting the abdominal aortal.The animal in fake operation group underwent peritoneotomy and the abdominal aortal was isolated without being ligated.After the operation the rats in drug group were treated with atorvastatin by intragastric administration(2mg/kg·d),while the others were treated with normal saline by intragastric administration at the same time.All rats were sacrificed 8 weeks after the operation then the heart weight to body ratio and left ventricular weight to body were measured.The expressions of interleukin 18(IL-18) and cardiotrophin(CT-1) in the cadiocyte were detected by reverse transcription polymerase chain reaction(RT-PCR).We also measured the thickness of left ventricular wall and the diameter of the cadiocyte through pathological examination.
Result Compared to control group,the heart weight to body ratio,the left ventricular weight to body,the expressions of IL-18 and CT-1 in myocardial hypertrophy group were significantly increased(p＜0.05).The thickness of left ventricular wall and the diameter of cadiocyte were higher in hypertrophy group than in the other groups(p＜0.05).While in the drug group these indexes were lower compared with the myocardial hypertrophy group(p＜0.05) and had no significant differences between control group(p≥0.05).
Conclusion.Atorvastatin can prevent the myocardial hypertrophy caused by pressure overload and these may attribute to its anti-inflammation effect.
[方法]40只wistar大鼠,随机分为心肌肥厚组(n=20),假手术组(n=10),空白对照组(n=10)。心肌肥厚组以缩窄腹主动脉的方法造成后负荷增大,从而引起心肌肥厚,假手术组采用相同的手术方法,但只分离腹主动脉,但不结扎,空白对照组不予处理。术后1周测量血压以确定造模是否成功。确认造模成功后心肌肥厚组再随机分为心肌肥厚对照组(n=10)及心肌肥厚药物组(n=10)。心肌肥厚药物组通过灌胃的方式给予阿托伐他汀2mg/kg·d,至术后8周,同时心肌肥厚组、假手术组及空白对照组给予等量的生理盐水灌胃。8周后处死大鼠,测量其心脏重量/体重、左心室重量/体重的比值,以及病理切片的左室壁厚度、心肌细胞直径,并通过逆转录PCR(RT-PCR)的方法测定心肌组织中心调理素(CT-1)和白细胞介素18(IL-18)的表达情况。
[结果]术后两周心肌肥厚组的血压较术前明显升高(P＜0.05),较假手术组及空白对照组也明显升高(p＜0.05)。与空白对照组比较心肌肥厚组的心脏重量/体重、左心室重量/体重、左室壁厚度和心肌细胞直径均明显增大(P＜0.05),CT-1及IL-18mRNA表达也明显升高(P＜0.05),而心肌肥厚药物组上述各项指标均较心肌肥厚对照组明显减少,而与空白对照组无差别(P≥0.05)。
[结论]阿托伐他汀可以防治压力负荷增大造成的心肌肥厚,并且伴随有炎症因子水平的降低,说明阿托伐他汀的这种作用可能与其抗炎作用有关。
Objective Myocardial hypertrophy which can be caused by many heart diseases is a independent risk factor of the motality of cardiovascular disease.The purpose of this study is to observe the effect of atorvastatin on the myocardial hypertrophy caused by pressure overload and to find out the possible mechanisms.
Method 40 wistar rats were randomized into myocardial hypertrophy group,drug group, fake operation group and control group.Pressure overload was achieved by surgical constricting the abdominal aortal.The animal in fake operation group underwent peritoneotomy and the abdominal aortal was isolated without being ligated.After the operation the rats in drug group were treated with atorvastatin by intragastric administration(2mg/kg·d),while the others were treated with normal saline by intragastric administration at the same time.All rats were sacrificed 8 weeks after the operation then the heart weight to body ratio and left ventricular weight to body were measured.The expressions of interleukin 18(IL-18) and cardiotrophin(CT-1) in the cadiocyte were detected by reverse transcription polymerase chain reaction(RT-PCR).We also measured the thickness of left ventricular wall and the diameter of the cadiocyte through pathological examination.
Result Compared to control group,the heart weight to body ratio,the left ventricular weight to body,the expressions of IL-18 and CT-1 in myocardial hypertrophy group were significantly increased(p＜0.05).The thickness of left ventricular wall and the diameter of cadiocyte were higher in hypertrophy group than in the other groups(p＜0.05).While in the drug group these indexes were lower compared with the myocardial hypertrophy group(p＜0.05) and had no significant differences between control group(p≥0.05).
Conclusion.Atorvastatin can prevent the myocardial hypertrophy caused by pressure overload and these may attribute to its anti-inflammation effect.
引文
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