Sang Ying, Zhou Li-jun, Jing Ling, Yuan Lin, Lu Li-xin, Zhang Qing-hui
First Clinical Hospital of Harbin Medical University, Harbin 150001, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2011 May;39(5):440-5.
To evaluate the effects of valsartan and carnitine on cardiomyocyte Calpain-1 and Bcl-xl expressions of dogs with chronic alcohol intake-induced cardiomyopathy.
Dogs were randomly assigned into 4 groups (n = 7 each): (1) alcohol fed (free access to 5%, 1(st) week; 10% 2(nd) week; 500 ml 25% bolus plus free access to 5% from 3 to 24 weeks, A); (2) alcohol + valsartan (5 mg×kg(-1)×d(-1), B); (3) alcohol + carnitine (300 mg×kg(-1)×d(-1), C); (4) Control (D). After six months, all animals were assessed for left ventricular (LV) function by echocardiography. The Bad and Bcl-xl protein expressions were evaluated by immunohistochemistry. The expression of Calpain-1 protein was determined with Western blot. Myocardial morphology was quantified on HE stained slices and under electron microscopy. The terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) was performed for apoptosis analysis.
Compared with group D, LVEDD and LVESD were significantly increased while EF and FS significantly decreased in group A. In alcohol fed group, expressions of Bad and Calpain-1 protein were significantly increased while Bcl-xl protein expression was downregulated, all changes could be significantly attenuated by intervention with valsartan and carnitine (all P < 0.05).
These data suggest that alcohol could promote cardiac myocyte apoptosis, reduce cardiac function and aggravate myocardial remodeling which valsartan and carnitine could reduce alcoholic cardiomyopathy by downregulating Calpain-1 and Bad protein expression and upregulating expression of Bcl-xl protein.
评估缬沙坦和肉碱对慢性酒精摄入诱导的犬心肌病心肌细胞钙蛋白酶-1和Bcl-xl表达的影响。
将犬随机分为4组（每组n = 7）：（1）酒精喂养组（第1周自由饮用5%酒精；第2周10%酒精；第3至24周500 ml 25%酒精推注加自由饮用5%酒精，A组）；（2）酒精+缬沙坦组（5 mg×kg⁻¹×d⁻¹，B组）；（3）酒精+肉碱组（300 mg×kg⁻¹×d⁻¹，C组）；（4）对照组（D组）。6个月后，通过超声心动图评估所有动物的左心室（LV）功能。通过免疫组织化学评估Bad和Bcl-xl蛋白表达。用蛋白质印迹法测定钙蛋白酶-1蛋白的表达。在苏木精-伊红（HE）染色切片和电子显微镜下对心肌形态进行定量分析。进行末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）法进行凋亡分析。
与D组相比，A组左心室舒张末期内径（LVEDD）和左心室收缩末期内径（LVESD）显著增加，而射血分数（EF）和缩短分数（FS）显著降低。在酒精喂养组中，Bad和钙蛋白酶-1蛋白表达显著增加，而Bcl-xl蛋白表达下调，缬沙坦和肉碱干预可显著减轻所有这些变化（所有P < 0.05）。
这些数据表明，酒精可促进心肌细胞凋亡，降低心脏功能并加重心肌重塑，缬沙坦和肉碱可通过下调钙蛋白酶-1和Bad蛋白表达以及上调Bcl-xl蛋白表达来减轻酒精性心肌病。
