核苷酸结合寡聚化结构域样受体蛋白3炎症小体与阿尔茨海默病患者神经炎症反应、氧化应激的相关性分析

Correlation of nucleotide-bindingoligomerization domain-like receptor 3 inflamma⁃some with neuroinflammatory response and oxidative stress in patients with Alzheim⁃er’s disease

目的探究核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体信号通路相关因子表达与阿尔茨海默病(AD)患者神经炎症反应及损伤和氧化应激的相关性。方法选取该院2017年5月—2019年5月收治的116例AD患者,依照简易精神状态量表(MMSE)评分为轻度组(53例)、中度组(45例)和重度组(18例),另选取同期于该院进行健康体检的40例健康体检者作为对照组,对比各组日常生活能力量表(ADL)、阿尔茨海默病评定量表-认知(ADAS-Cog)评分。检测比较NLRP3炎症小体信号通路相关因子[NLRP3、白细胞介素(IL)-1β及胱天蛋白酶(caspase)-1)]mRNA表达,炎症反应及损伤相关因子[核因子-κB(NF-κB)、神经胶质纤维酸性蛋白(GFAP)及IL-18]及氧化应激相关因子[超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)及谷胱甘肽过氧化物酶(GPX-3)]水平,分析NLRP3炎症小体信号通路相关因子与炎症反应及损伤和氧化应激的相关性。结果不同严重程度AD患者ADL评分及ADAS-Cog评分比较,差异具有统计学意义(P<0.05);且随着AD病情加重,患者ADL评分逐渐减低,ADAS-Cog评分升高(P<0.05)。AD患者NLRP3、IL-1β及Caspase-1 mRNA表达水平高于对照组(P<0.05),且随着病情加重,NLRP3、IL-1β及Cas⁃pase-1 mRNA表达水平逐渐升高(P<0.05)。AD患者炎症反应及损伤因子NF-κB、GFAP及IL-18水平高于对照组(P<0.05),且随着病情加重,NF-κB、GFAP及IL-18水平逐渐升高(P<0.05)。AD患者氧化应激因子SOD、CAT及GPX-3低于对照组(P<0.05),MDA高于对照组,且不同严重程度AD患者各指标比较,差异具有统计学意义(P<0.05)。相关性分析结果显示,NLRP3、IL-1β及Caspase-1 mRNA表达水平与炎症反应及损伤因子NF-κB、GFAP及IL-18表达呈正相关(P<0.05),与氧化应激相关因子SOD、CAT及GPX-3呈负相关,与MDA表达呈水平呈正相关(P<0.05)。NLRP3、IL-1β及Caspase-1 mRNA表达水平与AD患者ADL评分呈负相关,与ADAS-Cog评分呈正相关(P<0.05)。结论NLRP3在AD的发生与进展中具有重要作用,与其调节AD患者神经炎症反应及氧化应激有着密切关系。

Objective To investigate the correlation of the expression of nucleotide-binding oligomerization domain-like receptor 3(NLRP3) inflammasome signaling pathway-associated factors with neuroinflammatory response,neuroinflammatory injury,and oxidative stress in patients with Alzheimer’s disease(AD).Methods A total of 116 patients with AD who were admitted to our hospital from May 2017 to May 2019 were enrolled,and according to the Mini-Mental State Examination(MMSE) score,the patients were divided into mild group with 53 patients,moderate group with 45 patients,and severe group with 18 patients;40 individuals who underwent physical examination in our hospital during the same period of time were enrolled as control group.The above groups were compared in terms of Activities of Daily Living(ADL) score and Alzheimer’s Disease Assessment Scale-cognitive subscale(ADAS-Cog) score.The correlation of NLRP3 inflammasome signaling pathway-associated factors with inflammatory response,inflammatory injury,and oxidative stress was analyzed by measuring and comparing the mRNA expression of NLRP3 inflammasome signaling pathway-associated factors [NLRP3,interleukin-1β(IL-1β),and caspase-1],the levels of factors associated with inflammatory response and injury [nuclear factorkappa B(NF-κB),glial fibrillary acidic protein(GFAP),and interleukin-18(IL-18)],and the levels of oxidative stress-related factors [superoxide dismutase(SOD),malondialdehyde(MDA),catalase(CAT),and glutathione peroxidase(GPX-3)].Results There were significant differences in ADL and ADAS-Cog scores between the patients with different severities of AD(P<0.05),and ADL score gradually decreased and ADAS-Cog score gradually increased with the aggravation of AD(P<0.05).The patients with AD had significantly higher mRNA expression levels of NLRP3,IL-1β,and caspase-1 than the control group(P<0.05),and the mRNA expression levels of NLRP3,IL-1β,and caspase-1 gradually increased with the aggravation of the disease(P<0.05).The patients with AD had significantly higher levels of the factors associated with inflammatory response and injury NF-κB,GFAP,and IL-18 than the control group(P<0.05),and the levels of NF-κB,GFAP,and IL-18 gradually increased with the aggravation of the disease(P<0.05).The patients with AD had significantly lower levels of the oxidative stress-related factors SOD,CAT,and GPX-3 than the control group(P<0.05),and there were significant differences in the levels of these factors between the patients with different severities of AD(P<0.05).The correlation analysis showed that the mRNA expression levels of NLRP3,IL-1β,and caspase-1 were positively correlated with the expression levels of the factors associated with inflammatory response and injury NF-κB,GFAP and IL-18(P<0.05),negatively correlated with the levels of the oxidative stress-related factors SOD,CAT,and GPX-3,and positively correlated with the expression level of MDA(P<0.05).The mRNA expression levels of NLRP3,IL-1β,and caspase-1 were negatively correlated with ADL score and positively correlated with ADAS-Cog score in AD patients(P<0.05).Conclusions NLRP3 plays an important role in the development and progression of AD,possibly by regulating neuroinflammatory response and oxidative stress in AD patients.