重组人肿瘤坏死因子受体抗体融合蛋白联合缺血后适应减轻大鼠心肌缺血再灌注损伤  

Protective Effects of rhTNFR∶Fc Combined with Ischemic Postcondition on the Rat Heart Ischemia-Reperfusion Injury

作　　者：孙辉[1] 彭亚飞[1] 林伟[1] 钟玲[1] 

机构地区：[1]福建医科大学附属协和医院福建省冠心病研究所,福建省福州市350001

出　　处：《中国动脉硬化杂志》2010年第1期47-51,共5页Chinese Journal of Arteriosclerosis

摘　　要：目的研究重组人肿瘤坏死因子受体抗体融合蛋白、缺血后适应及其合用对大鼠心肌缺血再灌注损伤的保护作用。方法48只SD大鼠随机分为四组,四组大鼠均采取开胸结扎冠状动脉前降支1h再灌注6h,建立缺血再灌注动物模型,对照组不予任何处理;重组人肿瘤坏死因子受体抗体融合蛋白组在缺血后30min静脉给予重组人肿瘤坏死因子受体抗体融合蛋白溶液2mL/kg(1g/L);缺血后适应组在再灌注开始瞬间实施再灌注10s、缺血10s,共3个循环;联合治疗组缺血后30min静脉给予重组人肿瘤坏死因子受体抗体融合蛋白溶液2mL/kg(1g/L),再灌注开始瞬间实施再灌注10s、缺血10s,共3个循环。检测再灌注不同时间点血浆肿瘤坏死因子α活性的变化,测定再灌注末血清乳酸脱氢酶和肌酸激酶同工酶的活性、缺血和梗死面积、缺血区心肌Caspase-3、Bcl-2的活性和细胞凋亡。结果重组人肿瘤坏死因子受体抗体融合蛋白组、缺血后适应组、联合治疗组较对照组血浆乳酸脱氢酶、肌酸激酶同工酶、肿瘤坏死因子α(再灌注后30min、1h、3h及6h)活性、梗死面积、凋亡指数和Caspase-3活性均有明显降低(P<0.01),Bcl-2活性明显增加(P<0.01),其中联合治疗组效果最为显著(P<0.01),对肿瘤坏死因子α浓度的降低,再灌注30min和1h时缺血后适应组较重组人肿瘤坏死因子受体抗体融合蛋白组显著(P<0.01),再灌注3h和6h时重组人肿瘤坏死因子受体抗体融合蛋白组较缺血后适应组显著(P<0.01)。结论重组人肿瘤坏死因子受体抗体融合蛋白和缺血后适应均能抑制再灌注期间肿瘤坏死因子α活性,减少心肌细胞凋亡,二者联合治疗有叠加效应。Aim To study the recombinant human tumor necrosis factor-α receptorⅡ∶IgG Fc fusion protein（rhTNFR∶Fc）,ischemic postcondition（postcon）,and both combination on the prevention of myocardium ischemia/reperfusion injury.Methods 48 SD rats were randomly divided into four groups,all rats were subjected to 1 h of LAD occlusion followed by 6 h of reperfusion.In Control group,no interventions were applied;in rhTNFR∶Fc group,rhTNFR∶Fc solution（2 mL/kg,1 g/L）was administered intravenouslly at 30 min after ischemia;in postcon group∶ three cycles of 10 s of reperfusion and 10 s of reocclusion was applied immediately at the onset of reperfusion;in combination therapy group∶rhTNFR∶Fc solution（2 mL/kg,1 g/L）was administered intravenouslly at 30 min after ischemia,and three cycles of 10 s of reperfusion and 10 s of reocclusion was applied immediately at the onset of reperfusion.We measured plasma lactate dehydrogenase（LDH）,creatine kinase isoenzyme MB（CK-MB）,tumor necrosis factor-α（TNF-α）levels at different time after reperfusion and examined ischemic and infarct area,apoptosis,the activity of Caspase-3,Bcl-2 at risk myocardium at the end of reperfusion.Results rhTNFR∶Fc,ischemic postcondition,both combination reduced the plasma LDH,CK-MB,TNF-α levels（at 30 min,1 h,3 h,6 h after reperfusion）,infarct area,apoptotic myocytes,Caspase-3 activity,increased Bcl-2 activity when compared with controls（P0.01）.Ischemic postcondition reduced the plasma TNF-α more significantly than rhTNFR∶Fc at 30 min and 1 h after reperfusion（P0.01）.However,at 3 h and 6 h after reperfusion,rhTNFR∶Fc reduced the plasma TNF-α more significantly（P0.01）.Conclusion Both rhTNFR∶Fc and ischemic postcondition can inhibit TNF-α activity,attenuate myocyte apoptosis,and there is an additive effect when used in combination.

关 键 词：心肌缺血再灌注损伤 肿瘤坏死因子Α 缺血后适应 细胞凋亡 

分 类 号：R363[医药卫生—病理学]