IL-18BP对创伤性颅脑损伤大鼠焦虑样行为的改善作用及其机制  

Effect of IL-18BP on anxiety-like behavior in traumatic brain injury rats and its mechanism

作　　者：李妍 齐曼曼 缴宝杰[1] 李春雷 王春雷 常玉林[1] Li Yan;Qi Manman;Jiao Baojie;Li Chunlei;Wang Chunlei;Chang Yulin(Department of Anesthesiology,Cangzhou Central Hospital,Cangzhou 061000,China;不详)

机构地区：[1]沧州市中心医院麻醉科,沧州061000 [2]沧州市中心医院运动医学科,沧州061000

出　　处：《新医学》2023年第2期120-126,共7页Journal of New Medicine

基　　金：河北省医学科学研究课题(20220360)。

摘　　要：目的探讨IL-18结合蛋白(IL-18BP)对创伤性颅脑损伤(TBI)大鼠焦虑样行为的影响及其机制。方法采用随机数字表法将72只清洁级雄性SD大鼠分为3组各24只:假手术组(Sham组)、TBI组、TBI+IL-18BP组。Sham组仅开骨窗后缝合;TBI组应用自由落体法建立TBI模型;TBI+IL-18BP组大鼠建立TBI模型后经鼠尾静脉注射IL-18BP(1.5 mg/kg)。采用旷场实验和高架十字迷宫实验检测大鼠的焦虑样行为,采用免疫荧光染色技术检测大鼠杏仁核区各神经细胞的数量、NOD样受体热蛋白结构域相关蛋白3(NLRP3)和IL-18阳性星形胶质细胞百分比。采用ELISA法检测大鼠血清和脑脊液中IL-18的浓度。采用蛋白免疫印迹法检测大鼠杏仁核区焦亡相关蛋白:NLRP3、活化的Caspase-1、消皮素D的N端(N-GSDMD)的表达水平。结果与Sham组相比,TBI组、TBI+IL-18BP组30 d旷场实验中央区进入次数和活动时间减少,高架十字迷宫开放臂进入次数百分比和滞留时间百分比减少,血清和脑脊液中的IL-18浓度增加,杏仁核区星形胶质细胞激活增多,NLRP3与IL-18阳性的星形胶质细胞百分比上调,杏仁核区焦亡相关蛋白表达上调(P均<0.05)。与TBI组相比,TBI+IL-18BP组30 d中央区进入次数与活动时间增多,开放臂进入次数百分比和滞留时间百分比增加,血清和脑脊液中的IL-18的浓度降低,杏仁核区星形胶质细胞激活减少,NLRP3与IL-18阳性的星形胶质细胞百分比下调,杏仁核区焦亡相关蛋白表达下调(P均<0.05)。结论IL-18BP能在一定程度上减轻TBI大鼠的焦虑样行为,可能与抑制星形胶质细胞NLRP3炎性小体相关的细胞焦亡密切相关。Objective To evaluate the effect of IL-18 binding protein(IL-18BP)on anxiety-like behavior after traumatic brain injury(TBI)in rats and its related mechanism.Methods Seventy-two adult male SD rats were divided into 3 groups(all n=24)using the random number table method:sham-operated(Sham)group,TBI group,traumatic brain injury plus IL-18BP(TBI+IL-18BP)group.The skull was exposed and skin incisions were then closed without TBI in sham group.The rodent model of TBI was established using the weight-drop method.In TBI+IL-18BP group,IL-18BP was administered by tail vein at a dose of 1.5 mg/kg immediately after TBI.The changes in anxiety-like behaviors in rats were measured by the open field and elevated plus maze tests.The number of neuron and activated astrocytes as well as the percentage of NLRP3 and IL-18 positive astrocytes in amygdala region were detected by immunofluorescence assay.The concentration of IL-18 in serum and cerebrospinal fluid was detected by ELISA.The expression levels of NLRP3,activated Caspase-1(cl-Caspase-1),N-GSDMD in the amygdala were detected using western blot.Results At 30 d post-TBI,compared with the Sham group,rats in the TBI and TBI+IL-18BP groups had statistically less entry times and shorter time spending in the central square of the open field,significantly lower percentage of open arm entries and percentage of open arm time in the elevated plus maze tests,significantly increased concentration of IL-18 in the serum and cerebrospinal fluid,upregulated activation of astrocytes in the amygdala,higher percentage of NLRP3 and IL-18 positive astrocytes,as well as up-regulated expression levels of the pyroptosis-related proteins including NLRP3,cl-Caspase-1 and N-GSDMD(all P<0.05).While compared with the TBI group,rats in the TBI+IL-18BP group had statistically more entry times and longer time spending in the central square of the open field,significantly higher percentage of open arm entries and percentage of open arm time in the elevated plus maze tests,significantly lower concentration of

关 键 词：IL-18结合蛋白 创伤性颅脑损伤 焦虑 焦亡 

分 类 号：R651.15[医药卫生—外科学]