论文部分内容阅读
背景心肌细胞凋亡和心肌组织结缔组织生长因子(CTGF)表达的异常参与高血压心室重构的形成,阿托伐他汀能改善自发性高血压大鼠(SHR)左室重构,但其机制尚不完全明确。目的观察阿托伐他汀早期应用对SHR左室重构、心肌细胞凋亡和心肌CTGF表达的影响,探讨阿托伐他汀对SHR左室重构的影响及其可能机制。方法8周龄雄性SHR16只,随机分为2组:蒸馏水灌胃组(n=8)和阿托伐他汀组[50mg/(kg.d),n=8],同周龄同性别的WKY大鼠作为对照(WKY组,n=8)。用药12周,期间观察血压。12周后,以左室质量、左室质量与体质量比值、心肌细胞横径和心肌间质纤维沉积百分比评价左室重构;Westernblot方法测定心肌组织CTGF蛋白表达水平;TUNEL法检测心肌细胞凋亡率。结果与WKY组和蒸馏水灌胃组相比,阿托伐他汀治疗显著降低SHR血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇和收缩压水平;与蒸馏水灌胃组相比,阿托伐他汀组SHR左室质量与体质量比值显著降低[(4.0±0.4)比(4.7±0.4)mg/g]、心肌细胞横径减小[(16.2±2.8)比(19.0±1.0)μm]、心肌间质纤维沉积显著减少[(3.3±2.1)%比(4.5±1.8)%,均P<0.05];蒸馏水灌胃组[(1.9±0.3)%]的心肌细胞凋亡率显著低于WKY组[(4.7±0.7)%],而阿托伐他汀治疗12周的SHR心肌细胞凋亡率[(5.2±0.6)%]显著高于蒸馏水灌胃组[(1.9±0.3)%,P<0.05],与WKY组无显著差异;SHR心肌组织CTGF蛋白表达水平上升,阿托伐他汀治疗对该蛋白表达有显著抑制作用。结论SHR存在明显的左室重构,早期给予阿托伐他汀治疗可部分预防SHR左室重构,其机制可能与诱导心肌细胞凋亡、抑制心肌组织CTGF蛋白表达有关。
BACKGROUND Cardiomyocyte apoptosis and abnormal expression of connective tissue growth factor (CTGF) in myocardium are involved in the formation of hypertensive ventricular remodeling. Atorvastatin can improve left ventricular remodeling in spontaneously hypertensive rats (SHR), but its mechanism Not yet completely clear. Objective To observe the effects of early atorvastatin on left ventricular remodeling, myocardial apoptosis and CTGF expression in SHR and to investigate the effect of atorvastatin on left ventricular remodeling in SHR and its possible mechanism. Methods Eight male SHRs at 8 weeks of age were randomly divided into 2 groups: distilled water group (n = 8) and atorvastatin group (50 mg / (kg · d), n = 8] Rats served as controls (WKY group, n = 8). Medication for 12 weeks, during observation of blood pressure. After 12 weeks, left ventricular mass, left ventricular mass to body mass ratio, myocardial cell diameter and percentage of myocardial interstitial fibrosis were evaluated for left ventricular remodeling; CTGF protein expression in myocardium was detected by Western blot; TUNEL method was used to detect myocardial apoptosis Death rate. Results Compared with WKY group and distilled water group, atorvastatin significantly reduced total cholesterol, triglyceride, low density lipoprotein cholesterol and systolic blood pressure in SHR group. Compared with distilled water group, atorvastatin The ratio of left ventricular mass to body mass in SHR group was significantly lower than that in control group [(4.0 ± 0.4) vs. (4.7 ± 0.4) mg / g], and decreased in diameter of myocardial cells [(16.2 ± 2.8) vs (19.0 ± 1.0) μm] (3.3 ± 2.1)% vs (4.5 ± 1.8)%, all P <0.05]. The rate of myocardial cell apoptosis in distilled water group was significantly lower than that in WKY group [(1.9 ± 0.3)%] [(4.7 ± 0.7)%], while that of atorvastatin for 12 weeks was (5.2 ± 0.6)% in SHR group [(1.9 ± 0.3)%, P <0.05 ], No significant difference with WKY group; the expression of CTGF protein in SHR myocardium increased, atorvastatin treatment had a significant inhibitory effect on the protein expression. Conclusion There is a significant left ventricular remodeling in SHR. Early treatment with atorvastatin can prevent left ventricular remodeling in SHR partially. The mechanism may be related to inducing cardiomyocyte apoptosis and inhibiting CTGF protein expression in myocardium.