外源性一氧化碳对小肠缺血再灌注大鼠不同组织p38 MAPKs蛋白表达的影响

Effects of exogenous carbon monoxide on p38 MAPKs expression in rats with intestinal ischemia reperfusion injury

目的:探讨外源性一氧化碳(carbonmonoxide,CO)对小肠缺血再灌注(intestinal ischemia-reperfusion,IIR)所致多器官损伤防治作用的机制.方法:♂Wistar大鼠64只,随机分为8组,给予不同实验方法处理:A组:假手术对照组,不阻断肠系膜上动脉(superior mesenteric artery,SMA),其余手术过程同其他组;B组:小肠缺血再灌注组,经T型管吸入空气;C组:缺血前10 min CO吸入组,按吸入CO浓度(100μL/L,250μL/L)分为两个亚组(C1组和C2组);D组:再灌注开始时CO吸入组,按吸入CO浓度(100μL/L,250μL/L)分为两个亚组(D1组和D2组);E组:再灌注后60 min CO吸入组,按吸入CO浓度(100μL/L,250μL/L)分为两个亚组(E1组和E2组).实验结束时取不同组织以免疫蛋白印迹杂交法检测p38 MAPKs的密度表达.结果:与对照组A组比较,单纯IIR的B组的小肠、肺、肝组织中p38 MAPKs蛋白表达升高,但不显著(0.468±0.213 vs 0.474±0.151;0.439±0.111vs 0.482±0.103;0.622±0.112vs 0.654±0.016,all P>0.05);与单纯IIR的B组比较,外源性应用CO的C1、C2、D1、D2、E1、E2组的小肠、肺、肝组织中p38 MAPKs蛋白表达均明显增高(1.540±0.346,1.626±0.277,1.365±0.233,1.483±0.265,1.353±0.234,1.372±0.2731 vs 0.474±0.151;1.654±0.211,1.701±0.101,1.398±0.245,1.444±0.272,1.288±0.218,1.366±0.244 vs 0.482±0.103;1.695±0.234,1.723±0.213,1.423±0.221,1.586±0.254,1.322±0.261,1.411±0.296 vs 0.654±0.016,均P<0.05).结论:调节细胞内p38 MAPKs表达是外源性CO防治IIR所致多器官损伤作用的分子生物学基础之一.

AIM：To investigate the possible mechanism underlying the preventive effect of exogenous carbon monoxide（CO） on multiple organ injury induced by intestinal ischemia-reperfusion（IIR） in rats.METHODS：Sixty-four male Wistar rats were randomly and equally allocated into eight groups.IIR was induced in rats by clamping the superior mesenteric artery（SMA） for 60 min and reperfusing for 120 min.Group A and sham operation did not undergo SMA clamping.Group B underwent SMA clamping for 60 min and reperfusing for 120 min.Groups C1/C2,D1/D2,and E1/E2 inhaled 100 and 250 μL/L CO 10,60 min before SMA clamping and 60 min after reperfusion,respectively.The expression of p38 mitogen-activated protein kinases（MAPKs） in different tissues was detected by Western blot.RESULTS：Compared to Group A,the expression of p38 MAPKs in the intestine,lung and liver increased in Group B,but the differences were not significant（0.468 ± 0.213 vs 0.474 ± 0.151;0.439 ± 0.111 vs 0.482 ± 0.103;0.622 ± 0.112 vs 0.654 ± 0.016,all P 0.05）.Compared to Group B,a marked increase in p38 MAPKs expression in the intestine,lung and liver was detected in Groups C1/C2,D1/D2,and E1/E2（1.540 ± 0.346,1.626 ± 0.277,1.36 5± 0.233,1.483 ± 0.265,1.353 ± 0.234,1.372 ± 0.2731 vs 0.474 ± 0.151;1.654 ± 0.211,1.701 ± 0.101,1.398 ± 0.245,1.444 ± 0.272,1.288 ± 0.218,1.366 ± 0.244 vs 0.482 ± 0.103;1.695 ± 0.234,1.723 ± 0.213,1.423 ± 0.221,1.586 ± 0.254,1.322 ± 0.261,1.411 ± 0.296 vs 0.654 ± 0.016,all P 0.05）.CONCLUSION：Exogenous CO provides protection against IIR-induced multiple organ injury possibly by modulating the expression of p38 MAPKs in rats.