卡维地洛对免疫性心肌炎小鼠心肌凋亡调控蛋白影响

目的 观察卡维地洛对免疫性心肌炎小鼠心肌凋亡蛋白Bcl-2、Bax及Fas的影响,探讨其在免疫性心肌炎中的作用.方法 60只4～5周龄近交系雄性BALB/C小鼠,随机将小鼠分为3组:免疫性心肌炎模型组(模型组),卡维地洛干预组(干预组),空白对照组(对照组),每组20只.眼球取血后处死,留取心脏及血液标本.光镜观察各组小鼠心肌组织病理学改变,电镜观察心肌细胞超微结构,化学发光免疫法检测血清心肌肌钙蛋白I(cTnI)水平;免疫组化法检测心肌Bcl-2、Bax及Fas蛋白表达的含量;原位缺口末端标记(TUNEL)法检测心肌细胞凋亡情况.结果 模型组小鼠心肌细胞光镜下见大量炎症细胞浸润,电镜下可见细胞核固缩、染色质边集,对照组小鼠心肌细胞光镜下未见炎症细胞浸润,电镜下染色质边集不明显.模型组Bcl-2、Bax及Fas蛋白表达较对照组高(23.48±2.24 vs 6.64±1.60,26.15±2.02 vs 5.09±0.85,21.22±3.62 vs 5.86±1.37,P＜0.01);干预组与模型组比较,小鼠心肌组织炎症积分轻(2.60±0.3l vs 2.02±0.26,P＜0.05),电镜下细胞核固缩轻,心肌细胞Bcl-2、Bax及Fas蛋白表达低(17.13±1.94 vs 23.48±2.24,17.66±2.62 vs26.15±2.02,16.79±2.83 vs 21.22±3.62,P＜0.05),凋亡指数低[(16.61±4.67)%vs(24.51±4.70)%,P＜0.05],cTn-I水平低[(1.878±0.48)ng/ml vs(1.102±0.23)ng/ml,P＜0.05].结论 卡维地洛可减轻免疫性心肌炎小鼠心肌细胞凋亡,对免疫性心肌炎起一定的保护作用.

Abstract：

Objective To observe the effects of carvedilol on the expression of Bcl-2, Bax and Fas in autoimmune myocarditis (AM).Methods A total of 60 inbred male BALB/C mice 4-5 weeks of age were divided at random into 3 groups as follows: AM group ( n = 20), carvedilol group ( n = 20 ) and control group (n = 20).The mice were sacrificed after gathering blood specimens by taking out the eyeballs and hearts tissue.The histological and ultrastructural changes were observed under light microscope and electron microscope.The concentrations of cardiac troponin Ⅰ (cTn Ⅰ ) were detected by chemiluminescence immunoassay (CLIA).Immunohistochemistry (IHC) was performed to analyze the contents of Bcl-2, Bax and Fas, TUNEL to detect the apoptotic index in myocardial cells.Results There were large number of lymphocyte and monocyte infiltrates under light microscope and karyopyknosis and chromatin gathered along the nuclear membrane under electron microscope in AM group.There were no inflammations and chromatin gathering in group C.Compared with control group, the Bcl-2, Bax and Fas protein expression significantly elevated in AM group ( 23.48 ± 2.24 vs.6.64 ± 1.60,26.15 ± 2.02 vs.5.09 ± 0.85,21.22 ± 3.62 vs.5.86 ± 1.37, P ＜ 0.0l ) . The histopathologic scores ( 2.60 ± 0.31 vs.2.02 ± 0.26, P ＜ 0.05 ) and karyopyknosis of carvedilol group decreased as compared with AM group.The Bcl-2, Bax and Fas protein expression (17.13 ±1.94 vs.23.48 ±2.24,17.66 ±2.62 vs.26.15 ±2.02,16.79 ±2.83 vs.21.22 ±3.62, P ＜ 0.05 ), AI [( 16.61 ± 4.67 ) % vs.( 24.51 ± 4.70) %, P ＜ 0.05]and contents of cTnI [( 1.878± 0.48 ) ng/ml vs. ( 1.102 ± 0.23 ) ng/ml, P ＜ 0.05]also decreased in carvedilol group compared with AM group.Conclusion Carvedilol could protect against AM by alleviating cardiomyocyte apoptosis.

Effects of carvedilol on cardiomyocyte apoptosis in autoimmune myocarditis in mice

Objective To observe the effects of carvedilol on the expression of Bcl-2, Bax and Fas in autoimmune myocarditis (AM).Methods A total of 60 inbred male BALB/C mice 4-5 weeks of age were divided at random into 3 groups as follows: AM group ( n = 20), carvedilol group ( n = 20 ) and control group (n = 20).The mice were sacrificed after gathering blood specimens by taking out the eyeballs and hearts tissue.The histological and ultrastructural changes were observed under light microscope and electron microscope.The concentrations of cardiac troponin Ⅰ (cTn Ⅰ ) were detected by chemiluminescence immunoassay (CLIA).Immunohistochemistry (IHC) was performed to analyze the contents of Bcl-2, Bax and Fas, TUNEL to detect the apoptotic index in myocardial cells.Results There were large number of lymphocyte and monocyte infiltrates under light microscope and karyopyknosis and chromatin gathered along the nuclear membrane under electron microscope in AM group.There were no inflammations and chromatin gathering in group C.Compared with control group, the Bcl-2, Bax and Fas protein expression significantly elevated in AM group ( 23.48 ± 2.24 vs.6.64 ± 1.60,26.15 ± 2.02 vs.5.09 ± 0.85,21.22 ± 3.62 vs.5.86 ± 1.37, P ＜ 0.0l ) . The histopathologic scores ( 2.60 ± 0.31 vs.2.02 ± 0.26, P ＜ 0.05 ) and karyopyknosis of carvedilol group decreased as compared with AM group.The Bcl-2, Bax and Fas protein expression (17.13 ±1.94 vs.23.48 ±2.24,17.66 ±2.62 vs.26.15 ±2.02,16.79 ±2.83 vs.21.22 ±3.62, P ＜ 0.05 ), AI [( 16.61 ± 4.67 ) % vs.( 24.51 ± 4.70) %, P ＜ 0.05]and contents of cTnI [( 1.878± 0.48 ) ng/ml vs. ( 1.102 ± 0.23 ) ng/ml, P ＜ 0.05]also decreased in carvedilol group compared with AM group.Conclusion Carvedilol could protect against AM by alleviating cardiomyocyte apoptosis.