丁苯酞联合依达拉奉对急性脑梗死患者脑血管功能及NLRP3炎性小体信号通路的影响

Effects of butylphthalide combined with edaravone on cerebrovascular function and NLRP3 inflammatory vesicle signaling pathway in patients with acute cerebral infarction

目的探讨丁苯酞联合依达拉奉对急性脑梗死(ACI)患者脑血管功能及NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体信号通路的影响。方法选取义马煤业集团股份有限公司总医院2020年1月至2022年1月收治的120例ACI患者为研究对象,采用奇偶数分组法分为单一组60例和联合组60例。单一组患者予以依达拉奉治疗,联合组患者予以丁苯酞联合依达拉奉治疗。治疗14 d后比较两组患者的临床疗效,以及治疗前、治疗14 d后的脑血管功能[脑血管储备功能(CVR)、屏气指数(BHI)、搏动指数(PI)]、神经功能[中枢神经特异蛋白(S-100β)、神经元特异性烯醇化酶(NSE)、脑源性神经营养因子(BNDF)]、氧化应激指标水平[丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)]和NLRP3炎性小体信号通路相关蛋白[NLRP3、凋亡相关斑点样蛋白(ASC)、半胱氨酰天冬氨酸特异性蛋白酶1(Caspase-1)]水平。同时比较两组患者神经功能缺损[美国国立卫生研究所脑卒中评分(NIHSS)]和日常生活能力[Barthel指数评分(BI)]。结果联合组患者的治疗总有效率为95.00%,明显高于单一组的83.33%,差异有统计学意义(P<0.05);治疗后,联合组患者的CVR、BHI分别为(12.36±2.12)%、1.16±0.28,明显高于单一组的(10.24±2.01)%、0.84±0.22,PI为0.51±0.10,明显低于单一组的0.62±0.13,差异均有统计学意义(P<0.05);治疗后,联合组患者的血清S-100β、NSE、MDA水平分别为(0.41±0.09)ng/m L、(15.03±3.01)ng/m L、(4.78±1.03)nmol/mL,明显低于单一组的(0.56±0.12)ng/mL、(18.75±3.08)ng/mL、(8.96±1.38)nmol/mL,血清BNDF、GSH-Px、SOD水平分别为(2.86±0.42)U/mL、(113.02±17.62)U/L、(328.16±50.38)U/mL,明显高于单一组的(2.30±0.31)U/mL、(79.08±12.36)U/L、(255.08±40.12)U/m L,差异均有统计学意义(P<0.05);治疗后,联合组患者的NLRP3、ASC、Caspase-1表达量明显低于单一组,差异均有统计学意义(P<0.05);治疗后,联合组患者的NIHSS评分为(5.30±1.06)分,明显低于单一组的(8.79±1.33)分,BI评分为(78.63±7.01)分,明显高于单一组的(66.34±6.82)分,差异均有统计学意义(P<0.05)。结论丁苯酞联合依达拉奉治疗ACI可改善患者的脑血管功能、神经功能、神经缺损程度,降低氧化应激水平,其疗效可能与抑制NLRP3炎性小体信号通路有关。

Objective To investigate the effects of butylphthalide combined with edaravone on cerebrovascular function and the NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammatory vesicle signaling pathway in patients with acute cerebral infarction(ACI).Methods One hundred and twenty patients with ACI admitted to General Hospital of Yima Coal Industry Group Co.,Ltd.from January 2020 to January 2022 were selected and divided into a single group(60 cases)and a combined group(60 cases)using the odd-even grouping method.The patients in the single group were treated with edaravone,while those in the combined group were treated with butylphthalide combined with edaravone.After 14 days of treatment,the clinical efficacy of the two groups,as well as the levels of cerebrovascular function[cerebrovascular reserve function(CVR),breath holding index(BHI),pulsatile index(PI)],neurological function[central neurospecific protein(S-100β),neuron-specific enolase(NSE),brain-derived neurotrophic factor(BNDF)],oxidative stress indicators[malondialdehyde(MDA),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)],and NLRP3 inflammatory body signaling pathway related proteins[NLRP3,apoptosis-associated speckle-like protein(ASC),cysteinyl aspartate-specific protease 1(Caspase-1)]before and after treatment were compared between the two groups.The neurological deficits[National Institutes of Health Stroke Scale(NIHSS)]and daily living ability[Barthel Index Score(BI)]were also compared between two groups.Results The total effective rate of treatment in the combined group was 95.00%,significantly higher than 83.33%in the single group(P<0.05).After treatment,the CVR and BHI of patients in the combined group were(12.36±2.12)%and 1.16±0.28,respectively,significantly higher than(10.24±2.01)%and 0.84±0.22 in the single group;the PI of the combined group was 0.51±0.10,significantly lower than 0.62±0.13 of the single group;the differences were statistically significant(P<0.05).After treatment,serum S-100β,NSE,and MDA were(0.41±0.09)ng/mL,(15.03±3.01)ng/mL,and(4.78±1.03)nmol/mL in the combined group,respectively,significantly lower than(0.56±0.12)ng/mL,(18.75±3.08)ng/mL,and(8.96±1.38)nmol/mL of the single group(P<0.05).The serum levels of BNDF,GSH-Px,and SOD in the combined group were(2.86±0.42)U/mL,(113.02±17.62)U/L,and(328.16±50.38)U/mL,respectively,significantly higher than(2.30±0.31)U/mL,(79.08±12.36)U/L,(255.08±40.12)U/mL of the single group(P<0.05).After treatment,the expression levels of NLRP3,ASC,and Caspase-1 in the combined group were significantly lower than those in the single group,and the differences were statistically significant(P<0.05).After treatment,the NIHSS score of the combined group was(5.30±1.06)points,significantly lower than(8.79±1.33)points in the single group,and the BI score was(78.63±7.01)points,significantly higher than(66.34±6.82)points in the single group,with statistically significant differences(P<0.05).Conclusion The combination of butylphthalide and edaravone in the treatment of ACI can improve patients'cerebrovascular function,neurological function,degree of nerve defect,and reduce oxidative stress levels.Its efficacy may be related to the inhibition of NLRP3 inflammatory body signaling pathway.