摘要
目的:观察氯沙坦对心力衰竭大鼠骨骼肌萎缩程度的影响,分析抗凋亡蛋白Bcl-2和促凋亡蛋白Bax在该影响中的作用。方法:实验于2003-04/2004-04在郑州大学病理生理学教研室完成。①选用清洁级健康成年SD大鼠24只,雄性。按随机抽签法将大鼠分为3组:对照组、模型组和治疗组,每组8只。通过颈部一次性皮下注射野百合碱30mg/kg建立心力衰竭模型。治疗组:造模2周后灌胃氯沙坦混悬液10mg/(kg·d),共2周;对照组和模型组(造模)以等量生理盐水灌胃2周。②计算右心室肥大程度判定指标右心室壁质量/左心室+室间隔质量、右心室壁质量/体质量。计算骨骼肌萎缩程度的判定指标腓肠肌质量/体质量。采用脱氧核糖核酸末端转移酶介导的缺口末端标记法原位标记法计算凋亡指数。采用蛋白免疫印迹法检测腓肠肌Bcl-2和Bax蛋白的表达,并计算Bax/Bcl-2。③组间计量资料差异比较采用单因素方差分析和独立样本t检验。结果:SD大鼠24只均进入结果分析。①模型组右心室壁质量/左心室+室间隔质量和右心室壁质量/体质量明显高于对照组(t=4.64,5.63,P<0.01);模型组腓肠肌质量/体质量明显低于对照组(t=3.72,P<0.01);治疗组右心室壁质量/体质量明显低于模型组(t=2.48,P<0.05)。治疗组腓肠肌质量/体质量虽与模型组比较,差异不明显,但有增高的趋势。②模型组大鼠腓肠肌细胞凋亡率和Bax蛋白表达明显高于其他2组(t=3.75～17.48,P<0.05～0.01),模型组Bcl-2蛋白表达明显低于其他2组(t=6.19,4.49,P<0.01)。结论:氯沙坦可明显提高Bcl-2蛋白表达,降低Bax蛋白表达和骨骼肌细胞凋亡,从而达到减轻心力衰竭大鼠骨骼肌萎缩的趋势。
AIM： To explore the influence of losartan on level of skeletal muscle atrophy in rats with heart failure, and analyze the effects of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax.
METHODS： The experiment was carried out in the Department of Pathophysiology, Zhengzhou University from April 2003 to April 2004.（1） Twenty-four male adult SD rats of cleaning grade were selected and divided randomly into three groups： control group, model group and losartan group, with 8 rats in each group. Heart failure in rats was induced by a single subcutaneous injection of 30 mg/kg monocrotaline to establish models. Losartan group： Losartan suspension （produced by Hangzhou MSD Pharmaceutical Co.Ltd, batch number： 01020, 50 mg for a tablet） was administered by intragastric infusion, 10 mg/kg a day for two weeks. Control group and model group： Intragastric infusions of equal saline were given for two weeks. （2）Right ventricular hypertrophy was assayed by right ventricular mass （RVM）/left ventricle （LV）＋interventricular septum （LVS） mass and RVM/body weight （BW）. And gastrocnemius weight/BW ratio was served as degree of skeletal muscle atrophy. Apoptosis index was calculated with in situ labeling of terminal deoxynucleotidyl transferase- mediated nick-end labeling （TUNEL）. Expressions of gastrocnemius Bcl-2 and Bax protein were quantified with Western Blot. Bax/Bcl-2 was served as degree of apoptosis. （3）Differenees of measurement data between groups were compared with t test or one-way analysis of variance.
RESULTS： Totally 24 rats were involved into the result analysis. （1）RVM/ LV＋LVS mass and RVM/BW were significantly higher in the model group than in the control group （t=4.64, 5.63, P 〈 0.01）; However, gastrocnemius weight/BW ratio was significantly lower in the model group than in the control group （t=3.72, P 〈 0.01）. Compared with model group, RVM/BW was remarkably decreased （t=2.48, P 〈 0.05）, and with the insignificant difference, gastrocnemius weight/BW ratio tended to increase in losartan group. （2） Compared with other 2 groups, the gastrocnemius apoptosis and expression of Bax protein were obviously elevated in the model group （t=3.75-17.48, P 〈 0.05-0.01）, but the expression of Bcl-2 protein was obviously lower in the model group than in other 2 groups （t=6.19, 4.49, P 〈 0.01）.
CONCLUSION： Losartan can strikingly increase expression of Bcl-2 protein, decrease expression of Bax protein and skeletal apoptosis, which are responsible for relieving skeletal muscle atrophy in rats with heart failure.
出处
《中国临床康复》
CAS
CSCD
北大核心
2006年第40期43-45,共3页
Chinese Journal of Clinical Rehabilitation
