p38 MAPK通路在小型猪自体静脉移植模型中的作用研究

Study of p38 MAPK pathway in the autologous vein transplantation model of miniature pig

目的实验通过建立小型猪的冠脉搭桥模型,并给予高选择性的p38 MAPK通路抑制剂SB203580,探讨p38MAPK通路在静脉桥再狭窄中的作用。方法随机抽取30头小型巴马猪,随机分为假手术组、对照组、实验组。假手术组仅模拟手术,不做血管移植;对照组于手术前给予二甲基亚砜(DMSO)灌胃,后常规冠状动脉旁路移植术;实验组(SB203580组)在术前给予p38 MAPK的高度选择性抑制剂SB203580(3 mg/kg)灌胃,再进行冠状动脉旁路移植术; 3组均于1个月后取出桥静脉,进行HE染色观察内膜增生情况,Western blot法测定p38、p-p38的表达。结果 HE染色对照组内膜、中膜增生明显高于实验组,差异具有统计学意义(P <0. 05);实验组内膜、中膜增生明显高于假手术组,差异具有统计学意义(P <0. 05); Western blot结果显示对照组p38、p-p38高于实验组,差异具有统计学意义(P <0. 05);实验组p38、p-p38高于假手术组,差异具有统计学意义(P <0. 05)。结论 p38 MAPK通路参与了自体移植静脉的再狭窄过程,SB203580可显著减少内膜增生。

Objective To establish a mini-pig coronary artery bypass graft model and to give a highly selective p38 MAPK pathway inhibitor SB203580 to explore the role of p38 MAPK pathway in venous bridge restenosis.Methods Thirty small Bama pigs were randomly divided into sham operation group,control group and experimental group.Sham-operated group only simulated operation,not vascular graft.The control group received routine coronary artery bypass grafting.In the experimental group(SB203580 group),SB203580(3 mg/kg),a highly selective inhibitor of p38 MAPK,was given intragastrically before coronary artery bypass grafting.All the three groups were taken out of the bridge vein after 1 month,HE staining was used to observe the intimal hyperplasia,and the expressions of p38 and p-p38 were detected by Western blot.Results The intima-media thickness and neointimal hyperplasia in HE staining group were significantly lower than those in control group(P<0.05).The intima and media hyperplasia in experimental group were significantly higher than those in sham operation group(P<0.05).Western blot results showed that p38,p-p38 in the experimental group were lower than those in the control group,the difference was statistically significant(P<0.05).p38 and p-p38 in sham-operated group were lower than those in experimental group with statistical significance(P<0.05).Conclusion p38 MAPK pathway is involved in the process of restenosis in autologous vein.SB203580 can significantly reduce the inflammatory reaction and intimal hyperplasia.