基于NLRP3/Caspase-1/GSDMD信号通路探讨Ghrelin对大鼠创伤性脑损伤的保护作用  

Investigation of the protective effect of Ghrelin on traumatic brain injury in rats based on the NLRP3/Caspase-1/GSDMD signaling pathway

作　　者：王馨婉 赵智慧 翟秀丽 王晶 段伟琴 WANG Xin-wan;ZHAO Zhi-hui;ZHAI Xiu-li;WANG Jing;DUAN Wei-qin(Inner Mongolia Clinical Medical College,Inner Mongolia Medical University,Hohhot 010017;Department of Anesthesiology,Inner Mongolia People's Hospital,Hohhot 010010,China)

机构地区：[1]内蒙古医科大学内蒙古临床医学院,内蒙古呼和浩特010017 [2]内蒙古自治区人民医院麻醉科,内蒙古呼和浩特010010

出　　处：《解剖科学进展》2024年第6期637-640,共4页Progress of Anatomical Sciences

基　　金：内蒙古自治区人民医院院内基金(2021YN01);内蒙古自治区自然科学基金(2023LHMS08048);内蒙古医学科学院公立医院科研联合基金科技项目(2023GLLH0025)。

摘　　要：目的探讨胃饥饿素(Ghrelin)对大鼠创伤性脑损伤的作用及其对NLRP3/Caspase-1/GSDMD信号通路的影响。方法30只SPF级雄性SD大鼠随机分成对照组(Control)、模型组(TBI)和Ghrelin干预组(Ghrelin),每组10只,模型组大鼠采用Feeney自由落体撞击法制备大鼠创伤性脑损伤,Ghrelin组在造模后30 min经大鼠尾静注射Ghrelin(20μg/kg)。72 h后取脑组织,HE染色观察脑组织病理变化;干湿重比值法检测脑水肿;TUNEL染色法检测脑神经细胞凋亡;免疫荧光检测脑组织ASC斑块;Western blot检测脑组织NLRP3/Caspase-1/GSDMD信号通路相关蛋白表达水平;ELISA检测大鼠血浆中炎症因子IL-1β、IL-18含量。结果与TBI组相比,Ghrelin组大鼠的脑组织病理损伤明显改善,脑水肿减轻,脑组织神经细胞凋亡数量减少,脑组织ASC斑点形成数显著降低,NLRP3、Caspase-1与GSDMD蛋白表达水平下降,血清炎性因子IL-1β、IL-18含量显著下降。结论Ghrelin通过调节NLRP3/Caspase-1/GSDMD信号通路抑制细胞焦亡,改善大鼠创伤性脑损伤。Objective To investigate the effect of Ghrelin on traumatic brain injury in rats and the NLRP3/Caspase-1/GSDMD signaling pathway.Methods Thirty SPF-grade male SD rats were randomly divided into control group(Control),model group(TBI),and Ghrelin intervention group(Ghrelin),with 10 rats each.The Feeney free-fall impact method was used to induce traumatic brain injury in the rats of the model group,while rats in Ghrelin group were received a tail vein injection of Ghrelin at a dose of 20μg/kg,30 min after animal model preparation.After 72 hours,brain tissue was collected for HE staining to observe pathological changes.The wet-to-dry weight ratio method was used to measure brain edema.TUNEL staining was performed to detect neuronal apoptosis in brain of rats.Immunofluorescence method was used to detect ASC plaques in brain tissues of rats.Western blot was useed to measure the expressions of NLRP3,Caspase-1 and GSDMD in brain tissues,and ELISA was useed to measure the levels of IL-1β and IL-18 in serum of rats.Results Compared with the TBI group,the pathological injury in brain tissue of rats in Ghrelin group was significantly improved,the cerebral edema was alleviated,the number of apoptosis of nerve cells in brain tissue was decreased,the number of ASC spot formation in brain tissue was significantly decreased,and the expressions of NLRP3,Caspase-1 and GSDMD were decreased,the levels of IL-1β and IL-18 in serum were decreased significantly.Conclusions Ghrelin can inhibit pyrodeath and improve traumatic brain injury in rats by regulating NLRP3/Caspase-1/GSDMD signaling pathway.

关 键 词：胃饥饿素 创伤性脑损伤 NLRP3 CASPASE-1 

分 类 号：R651.15[医药卫生—外科学]