普罗布考通过p38MAPK途径对房颤动物模型心房肌细胞凋亡的影响

Influence of probucol on atrial myocyte apoptosis through p38MAPK pathway in animal model of atrial fibrillation

目的探究普罗布考通过p38MAPK途径对心房颤动(房颤,AF)动物模型心房肌细胞凋亡的影响。方法将36只大鼠随机分为Sham组、AF组和AF+普罗布考组(每组12只)。AF组和AF+普罗布考组大鼠经氯化钙和乙酰胆碱建立AF模型,AF+普罗布考组大鼠用普罗布考灌胃50 mg/kg 7 d。比较各组大鼠的心肌电生理、心房肌细胞凋亡、炎性反应和p38MAPK通路水平。结果AF组的有效不应期/90%动作电位时程(ERP/APD90)水平(0.39±0.05)低于Sham组(0.69±0.06,P<0.05),AF+普罗布考组的ERP/APD90水平显著高于AF组(P<0.05)。AF组的白细胞介素(IL-6)、肿瘤坏死因子(TNF-α)、凋亡指数高于Sham组(P<0.05),AF+普罗布考组的IL-6、TNF-α、凋亡指数低于AF组(P<0.05)。AF组的MKK6和p38MAPK水平显著高于Sham组(P<0.05),AF+普罗布考组的的MKK6和p38MAPK水平显著低于AF组(P<0.05)。结论普罗布考通过抑制p38MAPK通路减少AF大鼠模型的心房肌细胞的凋亡,从而调节心肌电生理水平。

Objective To discuss the influence of probucol on apoptosis of atrial myocytes through p38MAPK pathway in animal model of atrial fibrillation(AF).Methods Rats(n=36)were randomly divided into Sham group,AF group and AF+probucol group(each n=12).AF model was established by using calcium chloride and acetylcholine in AF group and AF+probucol group,and AF+probucol group was given orally probucol(50 mg/kg 7 d).The changes of myocardial electrophysiology,atrial myocyte apoptosis,inflammatory response and p38MAPK pathway level were compared among all groups.Results The ratio of effective refractory period to 90%action potential duration(ERP/APD90)was lower in AF group(0.39±0.05)than that in Sham group(0.69±0.06,P<0.05),and higher significantly in AF+probucol group than that in AF group(P<0.05).The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)and apoptosis index were higher in AF group than those in Sham group(P<0.05),and lower in AF+probucol group than those in AF group(P<0.05).The levels of MKK6 and p38MAPK were higher significantly in AF group than those in Sham group(P<0.05),and lower significantly in AF+probucol group than those in AF group(P<0.05).Conclusion Probucol can reduce atrial myocyte apoptosis through inhibiting p38MAPK pathway and regulate myocardial electrophysiological level in AF rat model.