标题：SAFE通路介导的炎症因子在大鼠心肌缺血再灌注致脑损伤中的作用

      作者：赵博，马莉，詹丽英，冷燕，袁泉，刘恋    (武汉大学人民医院麻醉科,湖北 武汉 430060)

      卷次： 2017年28卷20期

      【摘要】 目的 探讨生存活化因子增强通路 (SAFE)介导的炎症因子在大鼠心肌缺血再灌注致脑损伤中的作用。方法 24只雄性SD大鼠按随机数表法分为三组(n=8)：假手术组(Sham)、心肌缺血/再灌注组(IR)、心肌缺血/再灌注+AG490组(IR+AG490)。IR组及 IR+AG490组通过结扎大鼠冠状动脉左前降支 30 min,再灌注 120 min建立大鼠心肌缺血/再灌注模型。取大鼠脑组织, Western blot检测 Janus激酶 2 (Jak2)、信号转导子和转录激活子3 (STAT3)蛋白表达及炎症因子白介素 1 (IL-1), 白介素 6 (IL-6), 白介素 8 (IL-8), TUNEL法检测细胞凋亡, 比色法检测含半胱氨酸的天冬氨酸蛋白水解酶 3 (Caspase3)活性。结果 与 Sham组比较, IR组 p-Jak2 [(1.8±0.13) vs(1.0±0)]、p-STAT3 [(1.6±0.08) vs (1.0±0)]表达增高,炎症因子 IL-1 [(3.3±0.16) vs (1.0±0)]、IL-6 [(3.3±0.16) vs (1.0±0)]、IL-8 [(2.8±0.28) vs (1.0±0)]表达增多, TUNEL [(18.8±1.29) % vs (4.2±0.44)%]表达增多, Caspase3活性[(2.6±0.24) vs (1.0±0)]升高,差异均有统计学意义(P<0.05)；与 IR组比较, IR+AG490组 p-Jak2 [(1.3±0.09) vs (1.8±0.13)],p-STAT3 [(1.1±0.11) vs (1.6±0.08)]表达减少,炎症因子 IL-1 [(2.1±0.17) vs (3.3±0.16)]、IL-6 [(1.9±0.22) vs (3.3±0.16)]、IL-8 [(2.2±0.19) vs (2.8±0.28)表达降低, TUNEL [(13.2±1.03)% vs (18.8±1.29)%]表达降低, Caspase3活性 [(2.1±0.21)vs (2.6±0.24)]降低,差异均有统计学意义(P<0.05)。结论 抑制SAFE通路的激活可以降低其下游炎症因子的级联表达，从而减少细胞凋亡，减轻大鼠心肌缺血再灌注引起的脑损伤。
      【关键词】 生存活化因子增强通路；炎症因子；心肌缺血再灌注；脑损伤
      【中图分类号】 R-332 【文献标识码】 A 【文章编号】 1003—6350（2017）20—3269—03

Role of inflammatory factor in SAFE pathway on brain injury in rats induced by myocardial ischemiareperfusion.
ZHAO Bo, MA Li, ZHAN Li-ying, LENG Yan, YUAN Quan, LIU Lian. Department of Anesthesiology,Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, CHINA
【Abstract】 Objective To evaluate the role of inflammatory factor in survivor activating factor enhancement(SAFE) pathway on brain injury rats induced by myocardial ischemia reperfusion (IR). Methods Twenty-four maleSprague-Dawley rats were divided into 3 groups by random number table (8 cases in each group): Sham group, IRgroup, IR+AG490 group. Myocardial IR was induced by occlusion of the anterior descending branch of the left coro-nary artery for 30 min in IR group and IR+AG490 group. The rats were sacrificed after 120 min of reperfusion and thebrain were removed for the check of Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3),interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8). Apoptosis was detected by TUNEL assay and cyste-ine-containing aspartic proteolytic enzyme 3 (Caspase3) activity was detected by colorimetric assay. Results Com-pared with sham group, p-Jak2 [(1.8±0.13) vs (1.0±0)], p-STAT3 [(1.6±0.08) vs (1.0±0)], IL-1 [(3.3±0.16) vs (1.0±0)],IL-6 [(3.3±0.16) vs (1.0±0)], IL-8 [(2.8±0.28) vs (1.0±0)], TUNEL [(18.8±1.29)% vs (4.2±0.44)%], Caspase3 [(2.6±0.24) vs (1.0±0)] were significantly increased in IR group (P<0.05); compared with IR group, p-Jak2 [(1.3±0.09) vs (1.8±0.13)], p-STAT3 [(1.1±0.11) vs (1.6±0.08)], IL-1 [(2.1±0.17) vs (3.3±0.16)], IL-6 [(1.9±0.22) vs (3.3±0.16)], IL-8[(2.2±0.19) vs (2.8±0.28)], TUNEL [(13.2±1.03)% vs (18.8±1.29)%], Caspase3 [(2.1±0.21) vs (2.6±0.24)] were signifi-cantly decreased in IR + AG490 group (P<0.05). Conclusion Inhibiting the activation of SAFE pathway can reducebrain injury induced by myocardial IR in rats though decreasing the inflammatory factor of downstream.
      【Key words】 Survivor activating factor enhancement (SAFE) pathway; Inflammatory factor; Myocardial isch-emia reperfusion; Brain injury基金项目：湖北省自然科学基金(编号：2016CFB167，2017CFB267)；中央高校基本科研业务费专项基金(编号：2042017kf0147)