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背景:压力负荷可以导致肾素血管紧张素醛固酮系统激活,进而导致左室重构,卡托普利对这种重构具有逆转作用。目的:观察卡托普利逆转压力负荷增加大鼠左室重构的作用及其机制。设计:随机对照实验。单位:南京军区南京总医院中西医结合科,上海中医药大学附属曙光医院,河北医科大学博士后流动站。材料:试验于1998-01/12在上海中医药大学实验室完成。选取Wistar雄性大鼠153只,共做5次试验,只有第4次试验是选择9只大鼠,其余试验均为36只大鼠。方法:将每次试验所选取的36只Wistar雄性大鼠随机分成假手术组、模型组、鹿角方组3组。模型组造模4周后,双蒸水灌胃15mL/kg,1次/d,连续4周。假手术组只分离腹主动脉,不用银夹狭窄,4周后,同模型组。卡托普利组造模4周后,以卡托普利100mg/kg,1次/d,用双蒸水15mL/kg稀释后灌胃,连续4周。主要观察指标:卡托普利对大鼠左室质量指数、Ⅰ型胶原和Ⅲ型胶原mRNA的表达,血浆和心肌血管紧张素Ⅱ含量、血浆心钠素和血清醛固酮含量的影响。结果:153只大鼠均进入结果分析。在检测Ⅰ型胶原积分吸光度试验中假手术组死亡和卡托普利组各3只,模型组死亡1只,最终纳入29只大鼠。在检测Ⅲ型胶原积分吸光度试验中,假手术组死亡3只,模型组死亡4只,卡托普利组死亡2只,最终纳入27只大鼠。均因动物手术损伤而脱失。①左室质量指数比较:假手术组和卡托普利组明显低于模型组[(2.24±0.12)/1000,(2.67±0.40)/1000,(3.15±0.47)/1000,t=2.649,6.499,P<0.001,0.05]。②Ⅰ型胶原积分吸光度的改变:假手术组和卡托普利组明显低于模型组[(0.57±0.19,0.86±0.25,2.79±2.00),t=3.661,3.170,P<0.01,0.05]。③Ⅲ型胶原积分吸光度的改变:假手术组和卡托普利组明显低于模型组[(0.48±0.10,0.52±0.29,0.84±0.27),t=3.560,2.417,P<0.01,0.05]。④Ⅰ型胶原mRNA的表达:假手术组和卡托普利组明显低于模型组[(79.1±18.6)%,(51.7±16.0)%,(139.0±29.2)%,t=2.910,P<0.05]。⑤心肌血管紧张素Ⅱ比较:假手术组和卡托普利组明显低于模型组[(130.2±30.2)μg/g,(137.6±39.5)μg/g,(196.7±48.6)μg/g,t=4.026,P<0.01]。⑥血浆心钠素比较:假手术组和卡托普利组明显低于模型组[(170.6±51.6)μg/g,(202.5±64.2)μg/g,(339.3±115.4)μg/L,t=4.623,P<0.01]。结论:①卡托普利降低压力负荷增加大鼠心肌Ⅰ和Ⅲ型胶原及其mRNA的表达,具有逆转左室重构的作用;②卡托普利逆转左室重构的作用可能与降低循环血浆和局部心肌血管紧张素Ⅱ,血浆心钠素,血清醛固酮水平,影响Ⅰ和Ⅲ型胶原mRNA表达有关。
BACKGROUND: Pressure stress can lead to the activation of the renin-angiotensin aldosterone system, leading to left ventricular remodeling. Captopril has a reversal effect on this remodeling. Objective: To observe the effect of captopril on left ventricular remodeling induced by pressure overload in rats and its mechanism. Design: Randomized controlled experiment. Unit: Nanjing Military Region, Nanjing General Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine Shuguang Hospital, Hebei Medical University postdoctoral station. Materials: The experiment was performed in the laboratory of Shanghai University of Traditional Chinese Medicine from January to December 1998. A total of 153 Wistar male rats were selected and 5 trials were performed. Only the 4 trials selected 9 rats and the remaining 36 rats. Methods: Thirty-six Wistar male rats selected from each trial were randomly divided into sham operation group, model group and antler group. Four weeks after the model group was established, double distilled water was given into stomach at 15 mL / kg once daily for 4 weeks. Sham-operated group only isolated the abdominal aorta, without silver clip stenosis, 4 weeks later, with the model group. Captopril group 4 weeks after modeling, captopril 100mg / kg, 1 time / d, with double distilled water 15mL / kg diluted gastric perfusion, continuous 4 weeks. MAIN OUTCOME MEASURES: Effects of captopril on left ventricular mass index, expression of type Ⅰ collagen and type Ⅲ collagen mRNA, plasma and myocardial angiotensin Ⅱ, plasma atrial natriuretic peptide and serum aldosterone levels in rats. Results: All 153 rats were involved in the result analysis. In the detection of type I collagen integral absorbance test sham operation group and the captopril group of three deaths in the model group, one, eventually 29 rats. In the test of type Ⅲ collagen integral absorbance test, 3 were killed in the sham operation group, 4 in the model group, 2 in the captopril group, and 27 in the end. All due to surgical injuries and loss. ① Comparison of left ventricular mass index: sham group and captopril group were significantly lower than the model group [(2.24 ± 0.12) / 1000, (2.67 ± 0.40) / 1000, (3.15 ± 0.47) /1000, t = 6.499, P <0.001, 0.05]. (2) The change of integral of I collagen: sham group and captopril group were significantly lower than that of model group [(0.57 ± 0.19,0.86 ± 0.25,2.79 ± 2.00), t = 3.661,3.170, P <0.01,0.05]. (3) The changes of integrin Ⅲ integral absorbance: sham group and captopril group were significantly lower than those in model group [(0.48 ± 0.10,0.52 ± 0.29,0.84 ± 0.27), t = 3.560,2.417, P <0.01,0.05]. ④ The mRNA expression of typeⅠcollagen: The sham and captopril groups were significantly lower than those in the model group [(79.1 ± 18.6)%, (51.7 ± 16.0)%, (139.0 ± 29.2)%, t = 2.910, P <0.05 ]. ⑤Comparison of myocardial angiotensin Ⅱ: The sham group and captopril group were significantly lower than the model group [(130.2 ± 30.2) μg / g, (137.6 ± 39.5) μg / g, (196.7 ± 48.6) μg / g, t = 4.026, P <0.01]. ⑥ plasma atrial natriuretic peptide comparison: sham operation group and captopril group was significantly lower than the model group [(170.6 ± 51.6) μg / g, (202.5 ± 64.2) μg / g, (339.3 ± 115.4) μg / L, t = 4.623, P <0.01]. Conclusion: (1) Captopril reduced the expression of type I and type III collagens and mRNA in myocardium of rats, and reversed the effect of left ventricular remodeling. (2) Captopril reversed the effect of left ventricular remodeling and decreased the circulation Plasma and regional myocardial angiotensin Ⅱ, plasma atrial natriuretic peptide, serum aldosterone level, affecting Ⅰ and Ⅲ collagen mRNA expression.