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

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.%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 male Sprague-Dawley rats were divided into 3 groups by random number table (8 cases in each group): Sham group, IR group, 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 the brain 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 reduce brain injury induced by myocardial IR in rats though decreasing the inflammatory factor of downstream.