中国药物与临床
中國藥物與臨床
중국약물여림상
CHINESE REMEDIES & CLINICS
2015年
1期
14-17
,共4页
心肌再灌注损伤%细胞凋亡%大鼠,Wistar%AMP579
心肌再灌註損傷%細胞凋亡%大鼠,Wistar%AMP579
심기재관주손상%세포조망%대서,Wistar%AMP579
Myocardial reperfusion injury%Apoptosis%Rats,wistar%AMP579
目的：比较AMP579和腺苷对大鼠心肌缺血再灌注损伤的保护作用及作用机制。方法64只Wistar大鼠随机分为4组（每组各16只）。假手术组：开胸只穿线不结扎血管，麻醉维持150 min；缺血再灌注组（I/R）：结扎冠状动脉左前降支（LAD）30 min，再灌注120 min；腺苷组：结扎LAD 30 min后，股静脉缓慢滴注腺苷305 ng·g-1·min-1，持续5 min，而后再灌注120 min；AMP579组：结扎LAD 30 min后，股静脉缓慢滴注AMP579305 ng·g-1·min-1，持续5 min，而后再灌注120 min。采用红四氮唑（TTC）法测量心肌梗死范围，TUNEL法观察各组心肌细胞凋亡数量，免疫组织化学SP法和Western blot观察Bcl-2和Bax蛋白的表达。结果与I/R组相比，腺苷组及AMP579组心肌梗死范围均明显缩小（P＜0．01），心肌细胞凋亡率明显降低（P＜0．01），Bax表达水平明显降低，Bcl-2表达水平明显升高（P＜0．01），且AMP579组较腺苷组效果更为明显（P＜0．05）。结论 AMP579和腺苷均可缩小心肌梗死范围，对缺血再灌注损伤的心肌起保护作用，且AMP579作用优于腺苷，其作用机制可能是通过上调Bcl-2蛋白的表达和下调Bax蛋白的表达，抑制再灌注心肌细胞的凋亡来实现的。
目的：比較AMP579和腺苷對大鼠心肌缺血再灌註損傷的保護作用及作用機製。方法64隻Wistar大鼠隨機分為4組（每組各16隻）。假手術組：開胸隻穿線不結扎血管，痳醉維持150 min；缺血再灌註組（I/R）：結扎冠狀動脈左前降支（LAD）30 min，再灌註120 min；腺苷組：結扎LAD 30 min後，股靜脈緩慢滴註腺苷305 ng·g-1·min-1，持續5 min，而後再灌註120 min；AMP579組：結扎LAD 30 min後，股靜脈緩慢滴註AMP579305 ng·g-1·min-1，持續5 min，而後再灌註120 min。採用紅四氮唑（TTC）法測量心肌梗死範圍，TUNEL法觀察各組心肌細胞凋亡數量，免疫組織化學SP法和Western blot觀察Bcl-2和Bax蛋白的錶達。結果與I/R組相比，腺苷組及AMP579組心肌梗死範圍均明顯縮小（P＜0．01），心肌細胞凋亡率明顯降低（P＜0．01），Bax錶達水平明顯降低，Bcl-2錶達水平明顯升高（P＜0．01），且AMP579組較腺苷組效果更為明顯（P＜0．05）。結論 AMP579和腺苷均可縮小心肌梗死範圍，對缺血再灌註損傷的心肌起保護作用，且AMP579作用優于腺苷，其作用機製可能是通過上調Bcl-2蛋白的錶達和下調Bax蛋白的錶達，抑製再灌註心肌細胞的凋亡來實現的。
목적：비교AMP579화선감대대서심기결혈재관주손상적보호작용급작용궤제。방법64지Wistar대서수궤분위4조（매조각16지）。가수술조：개흉지천선불결찰혈관，마취유지150 min；결혈재관주조（I/R）：결찰관상동맥좌전강지（LAD）30 min，재관주120 min；선감조：결찰LAD 30 min후，고정맥완만적주선감305 ng·g-1·min-1，지속5 min，이후재관주120 min；AMP579조：결찰LAD 30 min후，고정맥완만적주AMP579305 ng·g-1·min-1，지속5 min，이후재관주120 min。채용홍사담서（TTC）법측량심기경사범위，TUNEL법관찰각조심기세포조망수량，면역조직화학SP법화Western blot관찰Bcl-2화Bax단백적표체。결과여I/R조상비，선감조급AMP579조심기경사범위균명현축소（P＜0．01），심기세포조망솔명현강저（P＜0．01），Bax표체수평명현강저，Bcl-2표체수평명현승고（P＜0．01），차AMP579조교선감조효과경위명현（P＜0．05）。결론 AMP579화선감균가축소심기경사범위，대결혈재관주손상적심기기보호작용，차AMP579작용우우선감，기작용궤제가능시통과상조Bcl-2단백적표체화하조Bax단백적표체，억제재관주심기세포적조망래실현적。
Objective To compare the protective effects and underlying mechanism of AMP579 and adenosine on myocardial ischemia reperfusion injury in rats. Methods Wistar rats (n=64) were divided into 4 groups (n=16 each). The sham operation group underwent thoracotomy with a stitch placed around but not ligating the artery and , maintenance anesthesia for 150 min; the ischemia and reperfusion group (I/R) had left anterior descending (LAD) coronary artery occluded for 30 min and reperfusion for 120 min; the adenosine group received slow irrigation of adenosine 305 ng·g-1·min-1 for 5 min via femoral vein after the 30 min LAD artery occlusion, then reperfusion for 120 min; the AMP579 group received slow irrigation of AMP579 305 ng·g-1·min-1 was for 5 min via femoral vein after the 30 min LAD occlusion, then reperfusion for 120 min. TTC method was used to measure area of myocardial infarction;TUNEL method was used to determine the number of apoptotic cardiomyocytes in each group; expressions of Bcl-2 and Bax protein were measured by immunohistochemical SP method and Western blotting. Results Compared with the Group I/R, the myocardial infarction area, the rate of cardiomyocyte apoptosis, and the expression level of Bax protein were significantly reduced (P<0.01) while the expression level of Bcl-2 was increased (P<0.01) in both adeno-sine group and AMP579 group, and these effects in AMP579 group were more significantly than in the adenosine group (P<0.05). Conclusion Both AMP579 and adenosine may be cardio-protective against the ischemia reperfusion injury by reducing the myocardial infarct. Besides, AMP579 has a better effect than adenosine. The underlying mech-anism may be up-regulation of Bcl-2, down-regulation of Bax, and suppression of cardiomyocyte apoptosis induced by reperfusion.
