中国组织工程研究
中國組織工程研究
중국조직공정연구
Journal of Clinical Rehabilitative Tissue Engineering Research
2013年
33期
6005-6012
,共8页
组织构建%组织构建与生物活性因子%生物活性因子%促红细胞生成素%SB203580%丝裂原活化蛋白激酶%心肌梗死%炎症因子%心脏重构%机制%信号路径%国家自然科学基金
組織構建%組織構建與生物活性因子%生物活性因子%促紅細胞生成素%SB203580%絲裂原活化蛋白激酶%心肌梗死%炎癥因子%心髒重構%機製%信號路徑%國傢自然科學基金
조직구건%조직구건여생물활성인자%생물활성인자%촉홍세포생성소%SB203580%사렬원활화단백격매%심기경사%염증인자%심장중구%궤제%신호로경%국가자연과학기금
背景：研究表明，炎症细胞因子可影响心肌梗死后的预后，在心脏重构的进程中起重要作用。同时促红细胞生成素的促红细胞生成之外的非造血效应也被广泛证实：促红细胞生成素可通过与靶细胞膜表面的促红细胞生成素受体结合而减少炎症反应，从而减少心肌缺血后的再灌注损伤。<br> 目的：观察重组人促红细胞生成素对大鼠急性心肌梗死后心脏重构中炎症因子表达的影响。<br> 方法：通过结扎左冠状动脉前降支建立SD大鼠急性心肌梗死模型，分为5组，假手术组注射生理盐水，手术对照组造模后注射生理盐水，SB203580组造模后注射p38 MAPK的高选择性阻断剂SB203580，促红细胞生成素组造模后注射促红细胞生成素注射液，促红细胞生成素+SB203580组造模后注射促红细胞生成素+SB203580混合液，分别在造模前、造模后1 d、1周、2周及4周进行尾静脉采血，酶联免疫吸附法检测血清中白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平变化。<br> 结果与结论：造模前各组大鼠血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α检测值差异均无显著性意义(P>0.05)。假手术组各时段白细胞介素1β、白细胞介素6、肿瘤坏死因子α检测值差异无显著性意义(P>0.05)，其余4组不同时段各因子检测值呈现造模后1 d最高，造模后4周回降的趋势(P<0.05)。造模后手术对照组血清各因子检测值较其他组升高明显，而假手术组血清各因子检测值均低于其他4组(P<0.05)；使用药物进行干预的3组中，促红细胞生成素+SB203580组各因子检测值较低(P <0.05)，而促红细胞生成素组与SB203580组各因子检测值差异无显著性意义(P>0.05)。提示重组人促红细胞生成素抑制了大鼠急性心肌梗死后心脏重构中炎症因子白细胞介素1β、白细胞介素6、肿瘤坏死因子α的表达，重组人促红细胞生成素抑制炎症因子表达的机制可能与转化生长因子β1-TAK1-p38 MAPK信号路径相关。
揹景：研究錶明，炎癥細胞因子可影響心肌梗死後的預後，在心髒重構的進程中起重要作用。同時促紅細胞生成素的促紅細胞生成之外的非造血效應也被廣汎證實：促紅細胞生成素可通過與靶細胞膜錶麵的促紅細胞生成素受體結閤而減少炎癥反應，從而減少心肌缺血後的再灌註損傷。<br> 目的：觀察重組人促紅細胞生成素對大鼠急性心肌梗死後心髒重構中炎癥因子錶達的影響。<br> 方法：通過結扎左冠狀動脈前降支建立SD大鼠急性心肌梗死模型，分為5組，假手術組註射生理鹽水，手術對照組造模後註射生理鹽水，SB203580組造模後註射p38 MAPK的高選擇性阻斷劑SB203580，促紅細胞生成素組造模後註射促紅細胞生成素註射液，促紅細胞生成素+SB203580組造模後註射促紅細胞生成素+SB203580混閤液，分彆在造模前、造模後1 d、1週、2週及4週進行尾靜脈採血，酶聯免疫吸附法檢測血清中白細胞介素1β、白細胞介素6、腫瘤壞死因子α水平變化。<br> 結果與結論：造模前各組大鼠血清白細胞介素1β、白細胞介素6、腫瘤壞死因子α檢測值差異均無顯著性意義(P>0.05)。假手術組各時段白細胞介素1β、白細胞介素6、腫瘤壞死因子α檢測值差異無顯著性意義(P>0.05)，其餘4組不同時段各因子檢測值呈現造模後1 d最高，造模後4週迴降的趨勢(P<0.05)。造模後手術對照組血清各因子檢測值較其他組升高明顯，而假手術組血清各因子檢測值均低于其他4組(P<0.05)；使用藥物進行榦預的3組中，促紅細胞生成素+SB203580組各因子檢測值較低(P <0.05)，而促紅細胞生成素組與SB203580組各因子檢測值差異無顯著性意義(P>0.05)。提示重組人促紅細胞生成素抑製瞭大鼠急性心肌梗死後心髒重構中炎癥因子白細胞介素1β、白細胞介素6、腫瘤壞死因子α的錶達，重組人促紅細胞生成素抑製炎癥因子錶達的機製可能與轉化生長因子β1-TAK1-p38 MAPK信號路徑相關。
배경：연구표명，염증세포인자가영향심기경사후적예후，재심장중구적진정중기중요작용。동시촉홍세포생성소적촉홍세포생성지외적비조혈효응야피엄범증실：촉홍세포생성소가통과여파세포막표면적촉홍세포생성소수체결합이감소염증반응，종이감소심기결혈후적재관주손상。<br> 목적：관찰중조인촉홍세포생성소대대서급성심기경사후심장중구중염증인자표체적영향。<br> 방법：통과결찰좌관상동맥전강지건립SD대서급성심기경사모형，분위5조，가수술조주사생리염수，수술대조조조모후주사생리염수，SB203580조조모후주사p38 MAPK적고선택성조단제SB203580，촉홍세포생성소조조모후주사촉홍세포생성소주사액，촉홍세포생성소+SB203580조조모후주사촉홍세포생성소+SB203580혼합액，분별재조모전、조모후1 d、1주、2주급4주진행미정맥채혈，매련면역흡부법검측혈청중백세포개소1β、백세포개소6、종류배사인자α수평변화。<br> 결과여결론：조모전각조대서혈청백세포개소1β、백세포개소6、종류배사인자α검측치차이균무현저성의의(P>0.05)。가수술조각시단백세포개소1β、백세포개소6、종류배사인자α검측치차이무현저성의의(P>0.05)，기여4조불동시단각인자검측치정현조모후1 d최고，조모후4주회강적추세(P<0.05)。조모후수술대조조혈청각인자검측치교기타조승고명현，이가수술조혈청각인자검측치균저우기타4조(P<0.05)；사용약물진행간예적3조중，촉홍세포생성소+SB203580조각인자검측치교저(P <0.05)，이촉홍세포생성소조여SB203580조각인자검측치차이무현저성의의(P>0.05)。제시중조인촉홍세포생성소억제료대서급성심기경사후심장중구중염증인자백세포개소1β、백세포개소6、종류배사인자α적표체，중조인촉홍세포생성소억제염증인자표체적궤제가능여전화생장인자β1-TAK1-p38 MAPK신호로경상관。
BACKGROUND:Studies have shown that inflammatory cytokines may influence the prognosis after myocardial infarction, and play an important role in the process of cardiac remodeling. The non-hematopoietic effects of <br> erythropoietin have been confirmed:erythropoietin can reduce the inflammatory reaction through bending with <br> the erythropoietin on the surface of target cel membrane, thus decreasing the reperfusion injury after myocardial ischemia. <br> OBJECTIVE:To observe the effect of recombinant human erythropoietin on the inflammatory factor expression during cardiac remodeling in rats with acute myocardial infarction. <br> METHODS: Sprague Dawley rat models of acute myocardial infarction were established through the ligation of the left anterior descending coronary artery. The rats were divided into five groups:sham operation group was <br> injected with normal saline;operation control group was injected with normal saline after modeling;SB203580 group was injected with highly selective p38 MAPK inhibitor SB203580 after modeling;erythropoietin group was injected with <br> erythropoietin after modeling;the erythropoietin+SB203580 group was injected with erythropoietin+SB203580 mixed solution after modeling. The tail vein blood samples were col ected before modeling, 1 day, 1 week, 2 weeks and 4 weeks after modeling, and then enzyme-linked immunosorbent assay was used to detect the levels of interleukin-1β, interlrukin-6 and tumor necrosis factor-α. <br> RESULTS AND CONCLUSION:There were no significant differences in the levels of interleukin-1β, interlrukin-6 and <br> tumor necrosis factor-αbetween groups before modeling (P>0.05). There were no significant differences in the levels of interleukin-1β, interlrukin-6 and tumor necrosis factor-αbetween different time points in the sham operation group (P>0.05), and the levels were highest at 1 day after modeling in the other four groups, and then decreased at 4 weeks after modeling (P<0.05). After modeling, the level of serum cytokines in the operation control group were higher than those in the other four groups, while level of serum cytokines in the sham operation group was lower than that in the other four groups (P<0.05);among the three groups intervened with drugs, level of serum cytokines was lower in the <br> erythropoietin+SB203580 group (P<0.05), while there was no significant difference in the level of serum cytokines between erythropoietin group and SB203580 group (P>0.05). Recombinant human erythropoietin can inhibit the expressions of inflammatory factors (interleukin-1β, interlrukin-6 and the tumor necrosis factor-α) during cardiac <br> remodeling after rat acute myocardial infarction, and the mechanism of recombinant human erythropoietin for inhibiting the expressions of inflammatory factors may related with the transforming growth factorβ1-TAK1-p38 MAPK signal pathway.
