【摘要】 目的探讨细胞凋亡在心肌肥大大鼠骨骼肌萎缩中的作用及氯沙坦对心肌肥大大鼠骨骼肌萎缩的影响.方法雄性SD大鼠42只随机分成3组(n=14)Ⅰ组(对照组),Ⅱ组(心肌肥大组),Ⅲ组(心肌肥大氯沙坦治疗组).Ⅱ组和Ⅲ组分别一次性腹腔注射野百合碱(30mg/kg)以诱导心肌肥大.2wk后,Ⅲ组大鼠用氯沙坦[10mg/(kg·d)]灌胃.再过2wk后全部处死动物,以腓肠肌(GAS)的质量和体质量比作为骨骼肌萎缩的指标.TUNEL法检测GAS细胞凋亡.免疫组化和Western Blot法检测GAS Bcl-2,Bax的表达,并把Bax/Bcl-2值作为凋亡的程度.结果与Ⅰ组比,Ⅱ组的GAS细胞凋亡率明显增加[(147.6±32.6)‰vs(4.1±1.8)‰,P<0.05],并且GAS出现了萎缩.与Ⅱ组比,Ⅲ组的GAS细胞凋亡率明显减少[(46.2±12.3)‰vs(147.6±32.6)‰,P<0.05],GAS萎缩减轻.Bcl-2的表达Ⅱ组比Ⅰ组明显减少(P<0.05),Bax的表达明显升高(P<0.05).而Ⅲ组与Ⅱ组相比Bcl-2的表达明显升高(P<0.05),Bax的表达明显减少(P<0.05).Ⅱ组GAS的Bax/Bcl-2值明显升高,而Ⅲ组Bax/Bcl-2值明显下降.结论细胞凋亡在心肌肥大大鼠骨骼肌萎缩中发挥着重要的作用,可能是骨骼肌萎缩的原因之一,氯沙坦可能通过改变Bax/Bcl-2值减轻心肌肥大大鼠骨骼肌的凋亡和萎缩.更多还原

【Abstract】 AIM: To explore the role of cell apoptosis in skeletal muscle atrophy in rats with myocardial hypertrophy and the effect of losartan on it. METHODS: Forty-two Sprague Dawley rats were randomly divided into 3 groups: group I (n=14, normal control group), group II (n=14, myocardial hypertrophy group) and group III (n=14, losartan group). Monocrotaline (30 mg/kg) was injected transperitoneally in group II and group III to induce myocardial hypertrophy. After 2 weeks, group III was treated with losartan [10 mg/(kg·d)] by gavage. After 2 additional weeks, the rats were killed. Gastrocnemius mass/body mass ratio served as the degree of muscle atrophy. Apoptotic cells in gastrocnemius were stained in situ by using TUNEL. Gastrocnemius Bcl-2 and Bax protein were quantified by immunhistochemistry and Western Blot. Bax/bcl-2 served as the degree of apoptosis. RESULTS: The ratio of apoptosis was higher in group II than that in group I [(147.6±32.6)‰ vs (4.1±1.8)‰, P< 0.05]. The ratio of apoptosis was lower in group III than that in group II [(46.2±12.3)‰ vs (147.6±32.6)‰, P< 0.05] . The atrophy of skeletal muscle in group II was more serious that in group I(P<0.05), but that in group III was less serious than that in group II. The expression of Bcl-2 in group II was significantly lower than that in group I(P<0.05), but the expression of Bax in group II was significantly higher than that in group I(P<0.05). The expression of Bcl-2 in group III was higher than that in group II(P<0.05)but the expression of Bax was lower that in group II(P<0.05). The ratio of Bax/Bcl-2 in group II was higher than that in group III. CONCLUSION: Cell apoptosis plays an important role in skeletal muscle atrophy in rats with myocardial hypertrophy and may be one of the factors causing skeletal muscle atrophy. Losarton can decrease skeletal muscle cell apoptosis and atrophy in myocardial hypertrophy rat through regulating the ratio of Bax/ Bcl-2.更多还原