卡托普利对肺气肿大鼠外周骨骼肌功能的影响

Effects of Captopril on peripheral skeletal muscle dysfunction in rats with emphysema

目的探讨卡托普利对肺气肿大鼠外周骨骼肌生物力学、病理形态学和氧化代谢的影响。方法将40只雄性SD大鼠随机分为正常对照组、卡托普利对照组、肺气肿组、肺气肿卡托普利干预组，每组10只。采用气管内滴注猪胰弹性蛋白酶方法复制大鼠肺气肿模型。卡托普利对照组和卡托普利干预组大鼠给予含50mg／L卡托普利的自来水。于模型复制20周末时，行大鼠原位腓肠肌生物力学测定和心脏解剖学指标评价；并检测肌纤维组分构成，毛细血管密度，肌细胞内脂褐素包涵体的含量以及肌肉组织匀浆中氧化代谢酶活性变化。结果卡托普利干预组大鼠腓肠肌抗疲劳耐力显著高于肺气肿组，肌力半数恢复时间[（96．7±44．2）s]较肺气肿组[（145．0±55．4）s]缩短（P〈0．05）；卡托普利干预组大鼠腓肠肌Ⅰ型纤维的比例[（24．8±4．4）％]较肺气肿组[（16．0±5．0）％]增加（P〈0．05），Ⅱ型肌纤维的比例[（75．2±7．2）％]较肺气肿组[（84．0±9．4）％]降低（P〈0．05），2组大鼠腓肠肌毛细血管密度差异无统计学意义（P〉0．05）；卡托普利干预组大鼠腓肠肌脂褐素包涵体的含量（2．4±0．6）较肺气肿组（3．2±0．4）降低（P〈0．05），抗氧化酶活性高于肺气肿组（P〈0．05）；卡托普利干预组大鼠肺组织病理形态学、血压、左右心室质量与肺气肿组差异无统计学意义（P〉0．05）。结论卡托普利可改善肺气肿大鼠外周骨骼肌纤维组分构成、提高抗氧化能力、减轻氧化损伤，改善疲劳耐力。

Objective To study the effects of captopril on peripheral skeletal muscle biomechanics, pathomorphology and oxidative metabolism in rats with emphysema. Methods The emphysema rat model was established by intracheal instillation of porcine pancreatic elastase. Forty male Sprague Dawley rats were randomly divided into 4 groups （n= 10 each） ： a normal control group, a captopril control group （captopril 50 mg/L in drinking water）, a emphysema group, and a captopril intervention group （emphysema model rats receiving captopril 50 mg/L in drinking water）. Twenty weeks after instillation, in situ mechanical properties of gastrocnemius and cardiac anatomic indexes were evaluated. Gastrocnemius fiber type composition and capillary density （CD） were assessed by using ATPase staining. Lipofuscin inclusions （LI/F） were determined with the ferric-ferricyanide reduction test technique. The muscle biopsy homogenate was used to measure the activity of superoxide dismutase （SOD）,catalase （CAT） and total antioxidant capacity （T-AOC）. Results Captopril increased antifatigue tolerance and the force recovery rate of gastrocnemius muscle [（96.7±44.2）s vs（145.0±55.4）s, P 〈 0.05] in rats with emphysema. Captopril increased the proportion of type Ⅰ fibers [（24.8 ±4.4）% vs （16.0±5.0）, P 〈0.05] ,with a reciprocal decrease in type Ⅱfibers [（75.2±7.2） % vs （84.0±9.4） %, P 〈0.05] in rats with emphysema,but had no effects on gastrocnemius CD. Captopril decreased LI/F inthegastrocnemius muscle of emphysema rats （2.4±0.6 vs 3.2±0.4, P 〈0.05）,and elevated the activity of SOD[（72.4±18.3）U/mg vs （55.3±16.2） U/mg, P 〈0.05],CAT [（14.3±5.4）U/mg pro vs （9.3±3.7） U/rag pro, P 〈0.05land T-AOC [（79.2±16.7） nmol/mg pro vs （62.1±13.4） nmol/ mg pro, P 〈0.05] in muscle homogenate of rats with emphysem. Captopril had no effect on pulmonary pathomorphologic or cardiac anatomic indices in rats with emphysema. Conclusions Captopril could enhance the antifatigue tolerance, improve the fiber type constitution, lower lipofusin inclusions and increase the antioxidant enzyme activities in the peripheral skeletal muscle of rats with emphysema.