Abstract: Objective To study the correlation between the activation of NOD-like receptor protein 3 (NLRP3) inflammasome and neurological damage in neonatal rat hyperbilirubinemia model.Methods A total of 36 3-days-old SPF-grade neonatal SD rats were randomly divided into control group,model group and VX group,with 12 rats in each group. The hyperbilirubinemia model of neonatal rats was established by intraperitoneal injection of 100 μg/g bilirubin in model group and VX group. The VX group was also given intraperitoneal injection of NLRP3 inflammasome inhibitor VX-765. The differences on bilirubin content in brain and serum,water content and ATP content in brain,Nissl staining and TUNEL staining,NSE and S100B contents in serum and the expression of NLRP3 inflammasome were analyzed among the three groups. Results The total bilirubin content,water content,TUNEL positive staining cell rate,NLRP3,ASC,cleaved-caspase-1,active-IL-1β,active-IL-18 expression levels in brain and serum total bilirubin,NSE,S100B contents in the model group were significantly higher than those in the control group (P<0.05). However,ATP content and the number of Nissl positive staining cells in the brain tissue were significantly lower than those in control group (P<0.05). The water content,TUNEL positive staining cell rate,cleaved-caspase-1,active-IL-1β,active-IL-18 expression level in brain and serum NSE,S100B contents in VX group were significantly lower than those in model group(P<0.05). ATP content and the number of Nissl positive staining cells in the brain tissue were significantly higher than those in model group (P<0.05). Conclusion NLRP3 inflammasome is involved in the process of nerve injury in neonatal rats with hyperbilirubinemia.

Key words: neonatal hyperbilirubinemia, NOD-like receptor protein 3, inflammasome, neurological damage

摘要： 目的 研究新生大鼠高胆红素血症模型脑组织中NOD样受体蛋白3(NLRP3)小体活化与神经损害的相关性。方法 选择3日龄的SPF级新生SD大鼠36只,随机分为对照组、模型组和NLRP3小体抑制剂VX-765组(VX组)各12只,模型组和VX组通过腹腔注射100 μg/g胆红素的方式建立新生大鼠高胆红素血症模型,VX组同时给予NLRP3小体抑制剂VX-765腹腔注射。比较3组间血清及脑组织中胆红素含量、脑组织含水量及ATP含量、Nissl染色及TUNEL染色、血清NSE及S100B含量、NLRP3炎性小体表达的差异。结果 模型组大鼠脑组织中总胆红素含量、含水量、TUNEL阳性染色染色细胞率、NLRP3、ASC、cleaved-caspase-1、active-IL-1β、active-IL-18的表达水平及血清中总胆红素、NSE、S100含量明显高于对照组,脑组织中ATP含量及Nissl阳性染色细胞数目明显低于对照组(P<0.05);VX组大鼠脑组织中含水量、TUNEL阳性染色细胞率、cleaved-caspase-1、active-IL-1β、active-IL-18的表达水平及血清中NSE、S100含量明显低于模型组(P<0.05),脑组织中ATP含量及Nissl阳性细胞数目显著高于对照组(P<0.05)。结论 新生大鼠高胆红素血症模型中NLRP3小体活化参与了神经损伤过程。

关键词: 新生儿高胆红素血症, NOD样受体蛋白3, 炎性小体, 神经损害