p38 MAPK在自体移植静脉中的表达及其意义
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Expression and significance of p38 mitogenactivated protein kinases in autogenous vein graft
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    目的:研究丝裂原活化蛋白激酶p38MAPK信号传导通路在自体移植静脉中的表达。方法: Wistar大鼠80只,建立自体移植静脉模型。术后随机分为6,24h,3,7d和2,4,6,8周等8组,于相应时点取材,半定量逆转录PCR检测移植血管中p38MAPK的mRNA表达,Western蛋白印迹定量检测p38的蛋白产物及磷酸化蛋白产物表达,原位杂交和免疫组化方法定位p38mRNA及蛋白表达。 结果:移植静脉术后6h p38的mRNA表达即较正常静脉明显增强 (P<0.01),并于术后2周达高峰,表达值为(59±26)%,与4,6,8周比较差异极显著(P<0.01)。Western蛋白印迹提示p38在移植2~4周达高峰,之后开始减少,8周时仍维持一定表达量(1/4~1/2)。原位杂交及免疫组化提示阳性表达多定位于移植血管中层或增生内膜中的血管平滑肌细胞(VSMCs)。结论 :p38 MAPK通路的激活参与了移植静脉的内膜增生以及血管重塑,可望成为防治移植静脉狭窄闭塞的治疗靶点。

    Abstract:

    Objective:To investigate the expression and significance of p38 mitogenactivated protein kinase (MAPK) in autogenous vein graft. Methods: Autogenous vein graft model was established by transplanting the right jugular vein to infrarenal abdominal aorta in 80 Wistar rats. Ten vein graft samples were harvested 6 hours, 24 hours, 3 days, 7 days, 2 weeks, 4 weeks, 6 weeks and 8 weeks after surgery,respectively. Reverse transcriptionPCR and in situ hybridization,Western blot and immunohistochemistry methods were used to detect the expression of protein and phosphorylation protein of p38 and p38mRNA. Results:The expression of p38 mRNA increased 6 hours after surgery and reached the peak on the second week after surgery (59%±26%),and significantly higher than that on 4,6,8 weeks( P<0.01 vs.), Expression of p38 detected by Western blot reached to the peak on 2 to 4 weeks, and decreased significantly to 1/4 to 1/2fold on 8 weeks after surgery. The positive cells were mostly located in the vascular smooth muscle cells(VSMCs) in the media and/or intimal hyperplasia of vein graft. Conclusions: The activation of p38 MAPK system in intimal hyperplasia and vascular remodeling after vein graft may become a new target of the therapy for stenosis or obliteration of vein graft.

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胡新华,杨军,杨德华,宋方明,辛世杰, 张强. p38 MAPK在自体移植静脉中的表达及其意义[J].中国普通外科杂志,2004,13(1):10-33.
DOI:10.7659/j. issn.1005-6947.2004.01.010

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  • 在线发布日期: 2004-01-25