摘要
目的观察5-HT2B受体阻断剂对去甲肾上腺素(NE)诱导的肥厚心肌组织中心肌细胞凋亡的影响。方法雄性SD大鼠24只,随机分为3组,每组8只,分别为对照组,肥厚组、实验组。采用腹腔注射NE(1.5 mg/kg,2次/d,28 d)的方法建立心肌肥厚动物模型,自第15天起实验组腹腔注射SB204741(5-HT2B受体阻断剂)2 mg/kg,2次/d,连续注射14 d。对照组腹腔注射相同体积的生理盐水2次/d,28 d。采用TUNEL法检测各组心肌组织中心肌细胞的凋亡情况,Western blot方法分析Bcl-2、Bax、Caspase-3的表达情况。结果对照组的心肌组织中几乎看不到凋亡的心肌细胞,肥厚组心肌组织中凋亡心肌细胞数量显著增多,同时Bcl-2/Bax表达比例显著降低,Caspase-3的表达显著升高;与肥厚组相比,实验组心肌组织中凋亡心肌细胞的数量显著减少,Bcl-2/Bax表达比例显著升高,Caspase-3的表达显著降低。结论应用5-HT2B受体阻断剂不仅可减轻NE诱导的心肌肥厚的程度,还可通过上调Bcl-2/Bax表达比率、降低Caspase-3的活性抑制心肌细胞的凋亡。
Objecive To observe the anti-apoptotic activity of 5-HT receptor antagonist in cardiac hypertrophy induced by norepinephrine in rats. Methods Experiments were performed on Sprague-Dawley rats (weighing 180-220 g). To induce ventricular hypertrophy, rats were injected with norepinephrine (i.p.,1.5 mg/kg) twice daily for 28 days. Starting on the Day 15, 5-HT2s receptor antagonist SB 204741 (i.p.,2 mg/kg,in study group,n=8) was injected twice daily for another 14 days in the norepinephrine-injected rats. In control group, normal saline (n=8) was injected twice daily for 28 days. Ratios of left ventricular weight to body weight (LVW/ BW) were measured after rats had been decapitated. And then authors applied TUNEL assay to detect cardiomyocyte apoptosis,Western blot method to detect the levels of Bcl-2,Bax and Caspase-3 protein. Results Apoptotic cardiomyocytes were rarely seen in the hearts of saline-treated rats,but TUNEL-positive nuclear staining increased significantly in the left ventricles of rats treated with NE. The number of TUNEL-positive nuclei in left ventricles of NE-treated rats decreased significantly following treatment with SB 204741. Following chronic NE treatment of rats,cardiac Bcl-2 protein levels decreased significantly,whereas Bax and caspase 3 protein levels increased. Blockade of 5-HT receptors with SB 204741 resulted in an increase in the Bcl-2/Bax ratio and decreased caspase-3 expression. Conclusion In the process of cardiac hypertrophy induced by norepinephrine, blockade of 5-HT2s receptor with SB204741 resulted in anti-apoptotic activity,as evidenced by an increase in the Bcl-2/Bax ratio and decreased caspase-3 expression.
出处
《实用医药杂志》
2014年第9期815-818,共4页
Practical Journal of Medicine & Pharmacy