NLRP3-Caspase-1-IL-1β通路在新生大鼠缺氧缺血性脑损伤中作用研究

The role of NLRP3—Caspase-1—IL-1βinflammasome pathway in hypoxic-ischemic encephalopathy in neonatal rats

目的:探讨NLRP3炎症小体通路在新生大鼠缺氧缺血性脑病中的作用,为临床靶向治疗新生儿缺氧缺血性脑病提供实验依据。方法:将7d龄新生SD大鼠随机分组为正常对照组(Control组)、假手术组(Sham组)及缺氧缺血性脑损伤组(HIE组);造模后6h、48h、72h和7d时间点进行取材,采用免疫组化技术检测NLRP3、Caspase-1、IL-1β的表达水平。结果:脑组织免疫组织化学检测,与Sham组及Control组比较,HIE组不同时间点的NLRP3、Caspase-1和IL-1β水平均明显增加,差异有统计学意义(P<0.01),且NLRP3、Caspase-1和IL-1β在HIE组6h均可见水平增高,随着时间延长表达逐渐增加,7d表达最明显,差异有统计学意义(P<0.01)。结论:新生SD大鼠缺氧缺血后脑损伤随时间演变逐渐加重,与炎症小体通路的NLRP3、Caspase-1、IL-1β的表达上调有关。新生大鼠缺氧缺血性脑病可能与NLRP3炎症小体通路的启动激活有关。

Objective:The role of NLRP3 inflammasome pathway in hypoxic-ischemic encephalopathy in neonatal ratsand to provide experimental basis for clinical targeted treatment of neonatal hypoxic-ischemic encephalopathy.Methods:Seven-day-old newborn SD rats were randomly divided into three groups:hypoxic-ischemic brain injury group(HIE group),sham operation group(Sham group)and normal control group(Control group).Materials were collected at 6h,48h,72h and 7d after the model was made.The immunohistochemistry was employed to observe the expressions of NLRP3,Caspase-1 and IL-1β.Results:Observation of motor behavior:Observation of brain tissue under Immunohistochemical staining.Compared with the Sham group and the Control group,the levels of NLRP3,Caspase-1 and IL-1βat different time points in the HIE group increased significantly.The difference was statistically significant(P<0.01).The levels of NLRP3,Caspase-1,and IL-1βwere all increased in the HIE group at 6 h.The expression gradually increased with time,and the expression was most significant at 7 days.The difference was statistically significant(P<0.01).Conclusion:The hypoxic-ischemic encephalopathy of 7-day-old newborn SD rats was successfully modeled.The brain damage of neonatal SD rats gradually increased with time after hypoxic-ischemia,which was related to the up-regulation of NLRP3,Caspase-1,IL-1βexpression in the inflammasome pathway.The hypoxic-ischemic encephalopathy of newborn rats may be related to the activation of the NLRP3 inflammasome pathway.