基础医学与临床
基礎醫學與臨床
기출의학여림상
BASIC MEDICAL SCIENCES AND CLINICS
2010年
3期
289-292
,共4页
郭晋村%黄卫斌%王挹青%谢良地
郭晉村%黃衛斌%王挹青%謝良地
곽진촌%황위빈%왕읍청%사량지
促红细胞生成素%细胞外基质%缺血再灌注损伤
促紅細胞生成素%細胞外基質%缺血再灌註損傷
촉홍세포생성소%세포외기질%결혈재관주손상
erythropoietin%extracellular matrix%ischemia-reperfusion injury
目的 探讨促红细胞生成素在心肌缺血再灌注损伤中对细胞外基质代谢的调节作用及其机制.方法 构建Langendroff大鼠离体心脏缺血再灌注模型,结合Western blot观测在促红细胞生成素及相应信号传导通路阻滞剂干预下,左室舒张末压(LVEDP)、梗死面积、MMPs及胶原Ⅰ/Ⅲ表达的变化.结果 促红细胞生成素可改善LVEDP[(19.8±0.2)mmHg vs (35.9±0.2)mmHg,IR组 vs EPO+IR组,P＜0.05],减少梗死而积(35.26%±7.1% vs 62.70%±7.2%,EPO+IR组 vs IR组,P＜0.05).在缺血再灌注损伤的过程中MMP2及MMP9表达均显著升高,而TIMP-4则显著减低.外源性EPO可逆转MMPs的激活.此外EPO则可促进胶原Ⅲ、Ⅰ的表达,并且这一保护作用可被MEK-Erk信号通路阻滞剂所阻断.结论 EPO通过MEK-Erk信号传导通路促进胶原Ⅰ/Ⅲ的合成,抑制MMPs的激活,抑制细胞外基质降解,在一定程度上减轻大鼠心肌缺血再灌注损伤.
目的 探討促紅細胞生成素在心肌缺血再灌註損傷中對細胞外基質代謝的調節作用及其機製.方法 構建Langendroff大鼠離體心髒缺血再灌註模型,結閤Western blot觀測在促紅細胞生成素及相應信號傳導通路阻滯劑榦預下,左室舒張末壓(LVEDP)、梗死麵積、MMPs及膠原Ⅰ/Ⅲ錶達的變化.結果 促紅細胞生成素可改善LVEDP[(19.8±0.2)mmHg vs (35.9±0.2)mmHg,IR組 vs EPO+IR組,P＜0.05],減少梗死而積(35.26%±7.1% vs 62.70%±7.2%,EPO+IR組 vs IR組,P＜0.05).在缺血再灌註損傷的過程中MMP2及MMP9錶達均顯著升高,而TIMP-4則顯著減低.外源性EPO可逆轉MMPs的激活.此外EPO則可促進膠原Ⅲ、Ⅰ的錶達,併且這一保護作用可被MEK-Erk信號通路阻滯劑所阻斷.結論 EPO通過MEK-Erk信號傳導通路促進膠原Ⅰ/Ⅲ的閤成,抑製MMPs的激活,抑製細胞外基質降解,在一定程度上減輕大鼠心肌缺血再灌註損傷.
목적 탐토촉홍세포생성소재심기결혈재관주손상중대세포외기질대사적조절작용급기궤제.방법 구건Langendroff대서리체심장결혈재관주모형,결합Western blot관측재촉홍세포생성소급상응신호전도통로조체제간예하,좌실서장말압(LVEDP)、경사면적、MMPs급효원Ⅰ/Ⅲ표체적변화.결과 촉홍세포생성소가개선LVEDP[(19.8±0.2)mmHg vs (35.9±0.2)mmHg,IR조 vs EPO+IR조,P＜0.05],감소경사이적(35.26%±7.1% vs 62.70%±7.2%,EPO+IR조 vs IR조,P＜0.05).재결혈재관주손상적과정중MMP2급MMP9표체균현저승고,이TIMP-4칙현저감저.외원성EPO가역전MMPs적격활.차외EPO칙가촉진효원Ⅲ、Ⅰ적표체,병차저일보호작용가피MEK-Erk신호통로조체제소조단.결론 EPO통과MEK-Erk신호전도통로촉진효원Ⅰ/Ⅲ적합성,억제MMPs적격활,억제세포외기질강해,재일정정도상감경대서심기결혈재관주손상.
Objective To investigate the influence of erythropoietin in the metabolism of extracellular matrix after myocardial ischemia-reperfusion injury.Methods The langendroff reperfusion system was applied to investigate the protective function of EPO in ischemia-reperfusion condition in rats.The effects of EPO on extracellular matrix were observed by Western blot and signal pathway blocker.The LVEDP and infarction area were observed at the same time.Results EPO significantly improved LVEDP [(19.8±0.2) mmHg vs (35.9±0.2) mmHg,IR group vs EPO +IR group,P＜0.05]and decreased infarction area (35.26%±7.13% vs 62.70%±7.23%,IR group vs EPO+IR group,P＜0.05).The expression of MMPs was significantly decreased and the expression of collagenase Ⅰ/Ⅲ was significantly enhanced by EPO (MMP2 53.2+2.6 vs 21.2+2.5;MMP9 57.6±3.1 vs 19.2±2.6;IR group vs IR+EPO group (P＜0.05);collagen Ⅰ 43.2±2.2 vs 11.4±2.3;collagen Ⅲ 55.3±3.2 vs 18.1 vs 2.3;IR+EPO group vs IR group (P＜0.05).This function can be inhibited by Mek-Erk inhibitor.Conclusion EPO plays a role in the metabolism of extracellular matrix by Mek-Erk signal pathway,which can protect the heart tissue from ischemia-reperfusion injury.
