Exendin-4对脑缺血再灌注损伤小鼠神经胶质细胞炎症反应抑制作用及机制研究  

Exendin-4 alleviates cerebral ischemia reperfusion injury by inhibiting glial inflammation

作　　者：庞伟 鲍布和 赫明萍 孙晓楠[3] PANG Wei;BAO Bu-he;HE Ming-ping;SUN Xiao-nan(Clinical Laboratory of characteristic medical center of PAP,Tianjin 300162,China)

机构地区：[1]武警特色医学中心检验科,天津300162 [2]复旦大学附属华东医院,上海200040 [3]解放军总医院第二医学中心,北京100853

出　　处：《武警后勤学院学报（医学版）》2021年第5期11-14,29,共5页Journal of Logistics University of PAP（Medical Sciences）

基　　金：中央保健课题(W2017BJ12)。

摘　　要：【目的】探讨胰高血糖素样肽-1受体激动剂Exendin-4(Ex-4)对脑缺血再灌注(ischemia/reperfusion,I/R)损伤小鼠神经胶质细胞炎症反应的抑制作用及其潜在机制。【方法】36只成年雄性C57BL/6J小鼠随机分为假手术(Sham)、大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)以及MCAO联合Ex-4(MCAO+Ex-4)组,每组12只。采用线栓法建立右侧大脑中动脉栓塞模型,再灌注开始即刻腹腔注射Ex-4(10μg/kg)。脑缺血再灌注48 h后分别进行神经功能缺陷评分(modified neurological severity score,mNSS)、脑梗死体积、胶质细胞激活状态以及炎症因子检测。【结果】与Sham组比较,I/R 48 h后MCAO组小鼠神经功能明显受损(8.5±1.5)分vs.(1.6±1.1)分,梗死体积百分比增加(35.3±2.1)%vs.(0.1±0.0)%,梗死区组织中神经胶质酸性蛋白(glial fibrillar acidic protein,GFAP)和Iba-1阳性细胞百分比升高GFAP(32.4±9.0)vs.(6.6±2.8)%;Iba-1(29.8±7.7)vs.(7.1±2.7)%。炎症因子:肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-1β(Interleukin-1β,IL-1β)和白细胞介素-6(Interleukin-6,IL-6)表达水平均上升(P<0.01)。与之相反,MCAO+Ex-4组小鼠的mNSS评分(5.1±1.6)分、梗死体积百分比(18.6±1.1)%、GFAP和Iba-1阳性细胞百分比(17.2±6.9)%和(13.3±4.9)%以及上述三种炎症因子均较MCAO组显著降低(P<0.05或P<0.01)。【结论】Exendin-4能够通过抑制神经胶质细胞炎症反应,减轻脑缺血再灌注损伤程度,改善神经功能恢复,有望成为缺血性卒中的潜在治疗药物。【Objective】To explore the effect of glucagon-like peptide-1 receptor agonist-Exendin-4(Ex-4) on cerebral ischemia reperfusion(I/R) injury in mice and its underlying mechanisms.【Methods】A total of 36 male C57 BL/6 J mice were randomly divided into the sham-operation(Sham), middle cerebral artery occlusion(MCAO), and MCAO+Ex-4 groups(n=12). The cerebral ischemia reperfusion(I/R) injury model was established by middle cerebral artery occlusion(MCAO), and Ex-4(10 μg/kg) was intraperitoneally administered immediately upon reperfusion. The neurological scores(mNSS), infarction volume, glial active state and pro-inflammatory cytokines were respectively examined after 48 h of MCAO.【Results】Compared with the Sham group, MCAO mice showed significant increase in the mNSS score [(8.5 ± 1.5) vs.(1.6 ± 1.1) scores], infarction volume [(35.3 ± 2.1) vs.(0.1 ± 0.0) % ], GFAP-positive astrocytes [(32.4±9.0) vs.(6.6±2.8) %], Iba-1-positive microglia [(29.8±7.7) vs.(7.1±2.7) %], and pro-inflammatory cytokines TNF-α, IL-1β, and IL-6(all P<0.01). In contrast, Ex-4 treatment attenuated the mNSS scores(5.1±1.6), infarction volume [(18.6±1.1) %], GFAP-positive astrocytes [(17.2±6.9) %], Iba-1-positive microglia [(13.3±4.9) %], and the levels of TNF-α, IL-1β, and IL-6 compared with those of MCAO group(P<0.05 or P<0.01).【Conclusion】Exendin-4 alleviates cerebral ischemia reperfusion injury byinhibiting glial inflammation, which indicates that it may be a novel medicine for the treatment of ischemic stroke.

关 键 词：胰高血糖素样肽-1受体激动剂 EXENDIN-4 脑缺血再灌注损伤 神经胶质细胞 炎症反应 

分 类 号：R392[医药卫生—免疫学]