EDDE联合依折麦布对高脂血症合并WSI患者血脂、炎症/神经通路及脑细胞凋亡因子的影响

Effect of edaravone dexborneol combined with ezetimibe on blood lipids,inflammation/neural pathways,and brain cell apoptosis factors in patients with hyperlipidemia and watershed infarction

目的探究依达拉奉右莰醇(EDDE)联合依折麦布在高脂血症合并分水岭脑梗死(WSI)患者治疗中的潜在机制。方法选取2021年3月至2023年12月郑州市第二人民医院收治的80例高脂血症合并WSI患者纳入研究,按随机数表法分为研究组和对照组各40例,对照组患者在常规治疗的基础上采用依折麦布治疗,研究组在对照组治疗的基础上联合EDDE治疗,连续治疗14 d。治疗后比较两组患者的临床疗效,以及治疗前后的血脂水平[高密度脂蛋白胆固醇(HDL-C)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)]、CD40/CD40L炎症信号通路[白介素-1(IL-1)、白介素-6(IL-6)、白介素-10(IL-10)、可溶性CD40配体(sCD40L)]、磷酸肌醇-3-激酶(PI3K)/苏氨酸蛋白激酶(AKT)神经信号通路、脑细胞凋亡因子[抗凋亡因子(Livin)、可溶性凋亡相关因子(sFas)、sFas配体(sFasL)]、功能恢复情况[神经功能缺损(NIHSS)、认知功能(MMSE)]。结果研究组患者的治疗总有效率为92.50%,明显高于对照组的75.00%,差异有统计学意义(P<0.05);治疗14 d后,研究组患者TC、TG、LDL-C明显低于对照组,HDL-C高于对照组,差异均有统计学意义(P<0.05);治疗14 d后,研究组患者IL-1、IL-6、sCD40水平分别为(8.12±1.25)pg/mL、(1.53±0.34)pg/mL、(185.29±45.32)pg/mL,明显低于对照组的(13.78±1.64)pg/mL、(2.55±0.40)pg/mL、(289.18±52.25)pg/mL,IL-10水平为(49.10±4.28)pg/mL,明显高于对照组的(37.75±5.44)pg/mL,差异均有统计学意义(P<0.05);治疗14 d后,研究组患者PMBC内的PI3K、AKT、mTOR蛋白表达分别为1.34±0.23、1.25±0.26、1.57±0.35,明显高于对照组的1.10±0.19、1.11±0.21、1.23±0.24,差异均有统计学意义(P<0.05);治疗14 d后,研究组患者的血清sFasL、sFas水平分别为(2.42±0.41)ng/mL、(3.65±0.47)ng/mL,明显低于对照组的(4.26±0.58)ng/mL、(6.04±0.59)ng/mL,Livin水平为(9.57±1.18)μmol/L,明显高于对照组的(7.42±1.05)μmol/L,差异均有统计学意义(P<0.05);治疗14 d后,研究组患者的NIHSS评分(7.46±1.62)分,明显低于对照组的(10.85±2.26)分,MMSE评分(21.32±3.14)分,明显高于对照组的(17.49±2.57)分,差异均有统计学意义(P<0.05)。结论EDDE联合依折麦布治疗高脂血症合并WSI能调控患者的CD40/CD40L炎症信号通路、PI3K/Akt神经信号通路及神经凋亡相关分子表达,促进患者认知功能和神经功能恢复,与单纯依折麦布治疗相比,联合EDDE治疗效果更好。

Objective To explore the potential mechanism of edaravone dexborneol(EDDE)combined with ezetimibe in the treatment of patients with hyperlipidemia and watershed infarction(WSI).Methods A total of 80 patients with hyperlipidemia and WSI admitted to the Second People's Hospital of Zhengzhou from March 2021 to December 2023 were enrolled and randomly divided into a study group and a control group,with 40 patients in each group.Patients in the control group received ezetimibe treatment on the basis of conventional treatment,while those in the study group received ezetimibe treatment in combination with EDDE treatment on the basis of conventional treatment,for a continuous period of 14 days.After treatment,the clinical efficacy of the two groups of patients was compared,as well as the blood lipid levels(highdensity lipoprotein cholesterol,HDLC;cholesterol,TC;triglycerides,TG;lowdensity lipoprotein cholesterol,LDLC),CD40/CD40L inflammatory signaling pathway(interleukin1,IL1;interleukin6,IL6;interleukin10,IL10;soluble CD40 ligand,sCD40L),phosphoinositide 3kinase(PI3K)/threonine protein kinase(AKT)neural signaling pathway,brain cell apoptosis factors(antiapoptosis factor,Livin;soluble apoptosisrelated factor,sFas;sFas ligand,sFasL),functional recovery(neurological impairment,NIHSS),cognitive function(Minimental State Examination,MMSE)before and after treatment.Results The total effective rate of treatment in the study group was 92.50%,which was significantly higher than 75.00%in the control group(P<0.05).After 14 days of treatment,the TC,TG,and LDLC levels in the study group were significantly lower than those in the control group,while the HDLC level was significantly higher than that in the control group,with statistically significant differences(P<0.05).After 14 days of treatment,the levels of IL1,IL6,and sCD40 in the study group were(8.12±1.25)pg/mL,(1.53±0.34)pg/mL,and(185.29±45.32)pg/mL,respectively,which were lower than(13.78±1.64)pg/mL,(2.55±0.40)pg/mL,and(289.18±52.25)pg/mL in the control group,and the level of IL10 was(49.10±4.28)pg/mL,which was higher than(37.75±5.44)pg/mL in the control group,with statistically significant differences(P<0.05).After 14 days of treatment,the expression of PI3K,AKT,and mTOR proteins in peripheral blood mononuclear cells of patients in the study group was 1.34±0.23,1.25±0.26,and 1.57±0.35,respectively,which were significantly higher than 1.10±0.19,1.11±0.21,and 1.23±0.24 in the control group(P<0.05).After 14 days of treatment,the levels of serum sFasL and sFas in the study group were(2.42±0.41)ng/mL and(3.65±0.47)ng/mL,respectively,which were significantly lower than(4.26±0.58)ng/mL and(6.04±0.59)ng/mL in the control group,and the level of Livin was(9.57±1.18)μmol/L,which was significantly higher than(7.42±1.05)μmol/L in the control group,with statistically significant differences(P<0.05).After 14 days of treatment,the NIHSS score of the patients in the study group was(7.46±1.62)points,which was significantly lower than(10.85±2.26)points of the control group,and the MMSE score was(21.32±3.14)points,which was significantly higher than(17.49±2.57)points of the control group,with statistically significant differences(P<0.05).Conclusion The treatment of hyperlipidemia with WSI by EDDE combined with ezetimibe can regulate the CD40/CD40L inflammatory signaling pathway,PI3K/Akt neural signaling pathway,and the expression of molecules related to neuronal apoptosis in patients,and also promote the recovery of cognitive function and neurological function.It showed a significant benefit over the treatment with ezetimibe alone.