摘要
目的探讨p38蛋白激酶(p38MAPK)在小肠移植早期排斥反应中肠黏膜上皮细胞凋亡机理中的作用。方法选用近交系SD和Wistar大鼠进行节段性小肠移植,实验分3组:同基因移植组(Wistar→Wistar组)、异基因移植组(SD→Wistar组)和异基因移植加环孢素A组(SD→Wistar+CsA组)。分别于移植术后1、3、5及7d采集移植肠管行病理学检查排斥反应,TUNEL法检测凋亡细胞,并行Westernblotting测定p38MAPK表达;同时,ELISA法测定血清TNFα活性。结果SD→Wistar组肠黏膜上皮细胞发生轻、中、重度排斥反应中存在细胞凋亡,凋亡细胞数随排斥反应的加重而增加(P<0.01);Wistar→Wistar组排斥反应轻微,凋亡细胞数无明显变化(P>0.05);SD→Wistar+CsA组随着CsA的应用,排斥反应逐渐得到控制,且凋亡细胞数也随着减少。SD→Wistar组及SD→Wistar+CsA组的血清TNFα随移植肠管上皮细胞凋亡的轻重而发生相应的变化(P<0.01)。p38MAPK在SD→Wistar组随凋亡细胞数增加而表达加强(P<0.01),Wistar→Wistar组p38MAPK表达无明显变化(P>0.05),在SD→Wistar+CsA组随凋亡细胞数而发生相应的变化(P<0.01)。小肠移植早期排斥反应中肠黏膜上皮细胞凋亡现象与p38MAPK呈正相关(r=0.875,P<0.01),血清TNFα与移植肠上皮细胞凋亡呈正相关(r=0.837,P<0.01),血清TNFα与p38MAPK亦呈正相关(r=0.826,P<0.01)。结论大鼠小肠移植排斥反应中存在肠黏膜上皮细胞凋亡现象,p38MAPK参与细胞凋亡信号转导过程并起重要作用。
Objective To explore the effects of p38 mitogen-activated protein kinase （MAPK） on apoptosis of small intestinal epithelial cells after transplantation in rats. Methods Small intestinal transplantation was performed in SDand Wistar rats. The recipients were divided into three groups： isograft group （Wistar→Wistar group）, allograft group （SD→Wistar group） and allograft ＋ cyclosporine A group （ SD→Wistar＋CsA group）. The grafts were harvested on day 1, 3, 5 and 7 after operation. All graft samples were subjected to histological examination. The apoptosis of graft epithelial cells was detected by TUNEL method, p38 MAPK was measured by Western-blotting method and serum TNF-α was determined by ELISA. Results Mild, moderate and severe reiection reaction occurred in the SD→Wistar group, it was showed that the number of apoptotic cells increased with the severity of the rejection reaction by TUNEL. In SD→Wistar group, the numbers of apoptotic cells were significantly higher than those of the other two groups （P〈0, 01）. The severity of rejection reaction in SD→Wistar＋CsA group was less than that of SD→Wistar group and the number of apoptotic cells increased with the severity of the rejection reaction （P〈0.01）, The level of serum TNF-α varied with the apoptotic degree of small intestinal epithelial cells in SD→Wistar group and SD→Wistar＋CsA group （P〈0.01）. The expression of p38 MAPK increased with the number of the apoptotic cells in SD→Wistar group and SD→Wistar＋CsA group （P〈0.01）, but there was no evident change in Wistar→Wistar group （P〉0.05）. The expression of p38 MAPK and the level of serum TNF-α were positively correlated with apoptosis in small intestinal rejection after transplantation （r=0. 875, P〈0. 01; r=0. 837, P〈 0.01）. p38 MAPK and TNF-α were also positively correlated （r= 0. 826, P〈0.01）, Conclusion Apoptosis plays an important role in small intestinal rejection, p38 MAPK is involved in apoptosis and is an impo
出处
《中国普外基础与临床杂志》
CAS
2006年第1期66-70,共5页
Chinese Journal of Bases and Clinics In General Surgery
关键词
小肠移植
排斥反应
细胞凋亡
肿瘤坏死因子-Α
P38蛋白激酶
Small intestinal transplantation Rejection reaction Cell apoptosis Tumor necrosis factor-α p38 mitogen activated protein kinase
