TRIM31通过抑制NLRP3炎性小体通路改善蛛网膜下腔出血大鼠早期脑损伤  

TRIM31 ameliorates early brain injury in rats with subarachnoid hemorrhage by inhibiting NLRP3 inflammasome pathway

作　　者：田密 曾进 聂伟[1] 李拥军 刘晓君[1] TIAN Mi;ZENG Jin;NIE Wei;LI Yongjun;LIU Xiaojun(Department of Internal MedicineNeurology,The First Affiliated Hospital of Hunan College of Traditional Chinese Medicine,Zhuzhou 412000,Hunan,China)

机构地区：[1]湖南中医药高等专科学校附属第一医院神经内科,湖南株洲412000

出　　处：《西部医学》2022年第5期675-680,共6页Medical Journal of West China

摘　　要：目的探讨三结构域蛋白31(TRIM31)对蛛网膜下腔出血(SAH)大鼠早期脑损伤的影响及其潜在机制。方法将60只雄性SD大鼠随机分成假手术组(sham组)、SAH模型组(SAH组)、阴性对照慢病毒干预组(Lv-NC组)和TRIM31过表达慢病毒干预组(Lv-TRIM31组),每组15只。除sham组外,其他各组均采用血管内穿刺法制备SAH大鼠模型,并于造模前24 h经侧脑室注射慢病毒进行干预。造模后24 h,采用改良Garcia评分评估各组大鼠神经功能,并检测脑组织含水量;TUNEL染色观察各组大鼠海马神经元凋亡情况;ELISA法检测大鼠海马组织中炎症因子IL-1β和IL-18表达水平;qRT-PCR和Western blot法检测大鼠海马组织TRIM31、NLRP3、ASC和Caspase-1 mRNA以及蛋白表达水平。结果与sham组比较,SAH组大鼠神经功能评分降低(P<0.001),脑组织含水量、海马神经元凋亡率、IL-1β和IL-18表达水平以及NLRP3、ASC和Caspase-1的mRNA和蛋白表达水平均升高(P<0.05),而TRIM31 mRNA和蛋白表达水平降低(P<0.05)。与SAH组比较,Lv-TRIM31组大鼠神经功能评分升高(P<0.001),脑组织含水量、海马神经元凋亡率、IL-1β和IL-18表达水平以及NLRP3、ASC和Caspase-1的mRNA和蛋白表达水平均降低(P<0.05),TRIM31 mRNA和蛋白表达水平升高(P<0.001),而Lv-NC组以上各指标无显著性变化(P>0.05)。结论过表达TRIM31可减轻SAH大鼠早期脑损伤,其机制可能与抑制NLRP3炎性小体通路有关。Objective To explore the effect of tripartite motif containing 31(TRIM31)on early brain injury in rats with subarachnoid hemorrhage(SAH)and its underlying mechanism.Methods A total of 60 male SD rats were randomly divided into sham group(sham),SAH model group(SAH),negative control lentivirus group(Lv-NC)and TRIM31 overexpressed lentivirus group(Lv-TRIM31),with 15 in each group.In addition to the sham group,SAH models were established by intravascular puncture in the other groups,and lentivirus was injected into brain of rats by lateral ventricle at 24 h before modeling.At 24 h after modeling,the neurological functions of rats in various groups were evaluated by modified Garcia test,and the content of brain water was measured.The apoptosis of hippocampal neurons was observed by TUNEL staining.The expression levels of inflammatory factors IL-1β and IL-18 in the hippocampus were detected using ELISA assay.The mRNA and protein expression levels of TRIM31,NLRP3,ASC and Caspase-1 were evaluated by qRT-PCR and Western blot.Results Compared with the sham group,the neurological score of rats in the SAH group was decreased(P<0.001),the content of brain water,the apoptosis rate of hippocampal neurons,the levels of IL-1β and IL-18 and the mRNA and protein expression levels of NLRP3,ASC and Caspase-1 were increased(P<0.05),while the mRNA and protein expression level of TRIM31 was decreased(P<0.05).Compared with the SAH group,the neurological score of rats in the Lv-TRIM31 group was increased(P<0.001),the content of brain water,the apoptosis rate of hippocampal neurons,the levels of IL-1β and IL-18 and the mRNA and protein expression levels of NLRP3,ASC and Caspase-1 were decreased(P<0.05),and the mRNA and protein expression level of TRIM31 was increased(P<0.05),while the above indicators in the Lv-NC group had no significant changes(P>0.05).Conclusion Overexpression of TRIM31 can alleviate early brain injury in rats with subarachnoid hemorrhage,and its mechanism may be related to inhibition of NLRP3 inflammasome pathway.

关 键 词：三结构域蛋白31 蛛网膜下腔出血 脑损伤 NLRP3炎性小体 

分 类 号：R743.35[医药卫生—神经病学与精神病学]