选择性头部亚低温对缺氧缺血性脑病新生儿血清细胞焦亡相关分子的影响

Effect of selective head cooling on serum pyroptosis-related molecules in neonates with hypoxic-ischemic encephalopathy

目的:探讨选择性头部亚低温(SHC)对新生儿缺氧缺血性脑病(HIE)新生儿血清细胞焦亡相关关键蛋白和细胞因子,包括半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)、白细胞介素(IL)-1β、IL-18水平的影响,以期了解SHC治疗HIE可能的神经保护机制。方法:选择确诊为HIE新生儿共45例(HIE组),同期选取正常新生儿10名作为对照组,其中HIE组按照临床分期分为轻度HIE组13例,中度HIE组20例,重度HIE组12例,并按照亚低温治疗纳入标准将中、重度HIE新生儿32例分为常规治疗组(常规组)15例和SHC治疗组(SHC组)17例。采用ELISA法检测并比较各组新生儿血清Caspase-1、IL-1β、IL-18水平。结果:轻、中、重度HIE组新生儿血清Caspase-1、IL-1β水平均高于对照组,且Caspase-1、IL-1β水平均随HIE临床分期加重而上升(P<0.05);重度、中度HIE组血清IL-18水平均高于对照组和轻度HIE组(P<0.05)。HIE新生儿血清Caspase-1、IL-1β、IL-18水平与HIE临床分期均呈明显正相关关系(rs=0.820、0.913、0.683,P<0.01)。SHC组和常规组治疗前血清Caspase-1、IL-1β、IL-18水平差异均无统计学意义(P>0.05),SHC组治疗24 h血清Caspase-1和48、72 h时血清Caspase-1、IL-1β、IL-18水平均明显低于常规组(P<0.01)。治疗48、72 h,SHC组Caspase-1、IL-1β、IL-18水平均低于0、24 h(P<0.05);常规组48 h时血清Caspase-1、IL-1β、IL-18水平均较0 h上升(P<0.05),72 h时IL-1β、IL-18水平仍高于0 h(P<0.05),而Caspase-1水平与0 h差异无统计学意义(P>0.05)。结论:SHC治疗HIE新生儿可通过减少细胞焦亡水平以达到神经保护作用。

Objective:To investigate the effects of selective head cooling(SHC)on the serum levels of key proteins and cytokines related to pyroptosis[including cysteinyl aspartate specific proteinase-1(Caspase-1),interleukin(IL)-1βand IL-18]in neonates with hypoxic-ischemic encephalopathy(HIE)in order to understand the possible neuroprotective mechanism of SHC in the treatment of HIE.Methods:A total of 45 neonates with HIE and 10 normal neonates during the same period were divided into the HIE group and control group,respectively.The HIE group was subdivided into the mild HIE group(13 cases),moderate HIE group(20 cases)and severe HIE group(12 cases)according to clinical staging.According to the cooling therapy criteria,32 cases moderate and severe HIE neonates were divided into the conventional treatment group(15 cases)and SHC group(17 cases).The serum levels of Caspase-1,IL-1βand IL-18 in all groups were detected using ELISA,and compared.Results:The serum levels of Caspase-1 and IL-1βin mild,moderate and severe HIE groups were higher than those in control group,and the levels of Caspase-1 and IL-1βincreased with the aggravating of clinical staging of HIE(P<0.05).The serum levels of IL-18 in moderate and severe HIE groups were higher than that in mild HIE group and control group(P<0.05).The serum levels of Caspase-1,IL-1βand IL-18 in neonates with HIE were significantly positively correlated with the clinical staging of HIE(rs=0.820,0.913 and 0.683,P<0.01).There was no statistical significance in the serum levels of Caspase-1,IL-1βand IL-18 between SHC group and conventional treatment group before treatment(P>0.05).The serum level of Caspase-1 at 24 h and levels of Caspase-1,IL-1βand IL-18 at 48 h and 72 h of treatment in SHC group were significantly lower than those in conventional treatment group(P<0.01).at 48 h and 72 h of treatment,the levels of Caspase-1,IL-1βand IL-18 in SHC group were lower than those at 0 h and 24 h(P<0.05).The serum levels of Caspase-1,IL-1βand IL-18 in conventional treatment group at 48 h of treatment increased compared with at 0 h(P<0.05),the levels of IL-1βand IL-18 at 72 h were still higher than that at 0 h(P<0.05),while there was no statistical significance in the level of Caspase-1 between 72 h and 0 h(P>0.05).Conclusions:The selective head cooling in the treatment of HIE can achieve neuroprotection by reducing the level of pyroptosis.