CAJ | 학술논문

目的评价缺血后处理对糖尿病大鼠心肌缺血再灌注诱发脑损伤的影响.方法雄性SD大鼠,体重220 ～ 280 g,腹腔注射链脲佐菌素60 mg/kg制备糖尿病模型.取模型制备成功的大鼠30只,采用随机数字表法,将其分为3组(n=10):假手术组(S组)、心肌缺血再灌注组(IR组)和缺血后处理组(P组).IR组和P组采用结扎左冠状动脉前降支的方法制备大鼠心肌缺血再灌注损伤模型.P组于再灌注前进行缺血后处理,再灌注10 s,缺血10 s,共3次.再灌注120 min时,断头处死大鼠取脑组织,光镜下观察病理学结果,采用TUNEL法测定细胞凋亡指数,采用免疫组化法测定IL-6、IL-8和IL-10的表达水平,采用Western blot法测定糖原合酶激酶-3β(GSK-3β)和磷酸化GSK-3β(pGSK-3β)的表达水平.结果与S组比较,IR组和P组脑组织细胞凋亡指数升高,IL-6和IL-8的表达上调,IL-10和pGSK-3β的表达下调(P＜0.01)；与IR组比较,P组脑组织细胞凋亡指数降低,IL-6和IL-8的表达下调,IL-10和pGSK-3β的表达上调(P＜0.01),病理学损伤减轻；3组间脑组织GSK-3β表达差异无统计学(P＞0.05).结论缺血后处理可减轻糖尿病大鼠心肌缺血再灌注诱发的脑损伤,其机制可能与抑制GSK-3β活性有关.
목적 평개결혈후처리대당뇨병대서심기결혈재관주유발뇌손상적영향.방법 웅성SD대서,체중220 ～ 280 g,복강주사련뇨좌균소60 mg/kg제비당뇨병모형.취모형제비성공적대서30지,채용수궤수자표법,장기분위3조(n=10):가수술조(S조)、심기결혈재관주조(IR조)화결혈후처리조(P조).IR조화P조채용결찰좌관상동맥전강지적방법제비대서심기결혈재관주손상모형.P조우재관주전진행결혈후처리,재관주10 s,결혈10 s,공3차.재관주120 min시,단두처사대서취뇌조직,광경하관찰병이학결과,채용TUNEL법측정세포조망지수,채용면역조화법측정IL-6、IL-8화IL-10적표체수평,채용Western blot법측정당원합매격매-3β(GSK-3β)화린산화GSK-3β(pGSK-3β)적표체수평.결과 여S조비교,IR조화P조뇌조직세포조망지수승고,IL-6화IL-8적표체상조,IL-10화pGSK-3β적표체하조(P＜0.01)；여IR조비교,P조뇌조직세포조망지수강저,IL-6화IL-8적표체하조,IL-10화pGSK-3β적표체상조(P＜0.01),병이학손상감경；3조간뇌조직GSK-3β표체차이무통계학(P＞0.05).결론 결혈후처리가감경당뇨병대서심기결혈재관주유발적뇌손상,기궤제가능여억제GSK-3β활성유관.
Objective To evaluate the effects of ischemic postconditioning on brain injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods Diabetes mellitus was induced by intraperitoneal streptozotocin 60 mg/kg and confirmed by blood glucose level ＞ 16.7 mmol/L.Thirty male Sprague-Dawley rats,weighing 220-280 g,in which diabetes mellitus was successfully induced,were randomly allocated into 3 groups (n =10 each) using a random number table:group sham operation (group S),group I/R and group ischemic postconditioning (group P).Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery in I/R and P groups.Group P received 3 cycles of 10 s reperfusion followed by 10 s ischemia at the end of myocardial ischemia.The rats were sacrificed at 120 min of reperfusion and the brains were removed for microscopic examination and for determination of cell apoptosis (by TUNEL) and expression of interleukin-6 (IL-6),IL-8,IL-10,glycogen synthase kinase-3 beta (GSK-3β) and phosphorylated GSK-3β (pGSK-3β) (by immuno-histochemistry).Apoptotic index was calculated.Results Compared with group S,apoptotic index was significantly increased,IL-6 and IL-8 expression was up-regulated,and IL-10 and pGSK-3β expression was downregulated in I/R and P groups (P ＜ 0.01).Compared with group I/R,apoptotic index was significantly decreased,IL-6 and IL-8 expression was down-regulated,and IL-10 and pGSK-3β expression was up-regulated in group P (P＜0.01).There was no significant difference in GSK-3β expression among the 3 groups (P ＞ 0.05).The pathologic changes were significantly attenuated in group P as compared with group I/R.Conclusion Ischemic postconditioning can attenuate brain injury induced by myocardial I/R in diabetic rats,and inhition of activity of GSK-3β may be involved in the mechanism.