基于高迁移率族蛋白B1/Toll样受体4信号通路分析血栓通注射液联合阿替普酶静脉溶栓治疗对急性脑梗死患者的机制研究

Mechanism of Xueshuantong injection combined with intravenous thrombolysis with alteplase in treatment of patients with acute cerebral infarction based on high mobility group protein B1/Toll-like receptor 4 signaling pathway

  • 摘要:
    目的 基于高迁移率族蛋白B1/Toll样受体4(HMGB1/TLR4)信号通路分析血栓通注射液联合阿替普酶静脉溶栓治疗对急性脑梗死(ACI)患者的作用机制。
    方法 将106例ACI患者随机分为对照组(n=53)与研究组(n=53)。对照组进行阿替普酶静脉溶栓治疗,研究组在对照组基础上应用血栓通注射液治疗。比较2组临床疗效与不良反应,治疗前及治疗后7、14 d的美国国立卫生研究院卒中量表(NIHSS)评分,治疗前后的外周血单个核细胞内HMGB1 mRNA、TLR4 mRNA表达水平及血清中HMGB1、TLR4蛋白含量,以及治疗前后炎症因子白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。采用Pearson检验和Spearman检验分析ACI患者外周血单个核细胞内HMGB1 mRNA、TLR4 mRNA表达水平及血清中HMGB1、TLR4蛋白含量与NIHSS评分、疗效总有效率的相关性。
    结果 治疗后7、14 d时,研究组NIHSS评分低于对照组,差异有统计学意义(P < 0.05);治疗后, 2组HMGB1 mRNA、TLR4 mRNA表达水平较治疗前降低,且研究组HMGB1 mRNA、TLR4 mRNA表达水平低于对照组,差异有统计学意义(P < 0.05);治疗后, 2组血清HMGB1、TLR4蛋白含量较治疗前降低,且研究组血清HMGB1、TLR4蛋白含量低于对照组,差异有统计学意义(P < 0.05);治疗后, 2组血清TNF-α、IL-6水平低于治疗前,且研究组血清TNF-α、IL-6水平低于对照组,差异有统计学意义(P < 0.05)。对照组总有效率为75.47%, 研究组总有效率为94.34%, 差异有统计学意义(P < 0.05);对照组不良反应总发生率为9.43%, 研究组不良反应总发生率为15.09%, 差异无统计学意义(P>0.05)。Pearson检验显示, ACI患者外周血单个核细胞内HMGB1 mRNA、TLR4 mRNA表达水平及血清中HMGB1、TLR4蛋白含量与NIHSS评分呈正相关(r=0.431、0.443、0.396、0.375, P均 < 0.001);Spearman检验显示, ACI患者外周血单个核细胞内HMGB1 mRNA、TLR4 mRNA表达水平及血清中HMGB1、TLR4蛋白含量与疗效总有效率呈负相关(r=-0.536、-0.481、-0.475、-0.506, P均 < 0.001)。
    结论 血栓通注射液联合阿替普酶静脉溶栓治疗能有效改善ACI患者神经功能并降低机体炎症水平,其机制可能与下调HMGB1/TLR4信号通路有关。

     

    Abstract:
    Objective To analyze the mechanism of Xueshuantong injection combined with intravenous thrombolysis with alteplase in the treatment of patients with acute cerebral infarction (ACI) based on the high mobility group protein B1 (HMGB1)/Toll-like receptor 4 (TLR4) signaling pathway.
    Methods A total of 106 ACI patients were randomly divided into control group (n=53) and study group (n=53). The control group received intravenous thrombolysis with alteplase, while the study group received Xueshuantong injection treatment on the basis of the control group. Clinical efficacy and adverse reactions, the National Institutes of Health Stroke Scale (NIHSS) scores before treatment and on the 7th and 14th day after treatment, the expression levels of HMGB1 mRNA and TLR4 mRNA in mononuclear cells of peripheral blood before and after treatment as well as the protein contents of HMGB1 and TLR4 in serum, and the levels of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) before and after treatment were compared between two groups. Pearson test and Spearman test were used to analyze the correlations of the expression levels of HMGB1 mRNA and TLR4 mRNA in mononuclear cells of peripheral blood and the protein contents of HMGB1 and TLR4 in serum with the NIHSS score and the total effective rate in patients with ACI.
    Results The NIHSS score of the study group was significantly lower than that of the control group at 7 and 14 days after treatment (P < 0.05); after treatment, the expression levels of HMGB1 mRNA and TLR4 mRNA in both groups decreased significantly when compared to those before treatment, and the expression levels of HMGB1 mRNA and TLR4 mRNA in the study group were significantly lower than those in the control group (P < 0.05); after treatment, the serum protein contents of HMGB1 and TLR4 in both groups decreased significantly when compared to those before treatment, and the serum protein contents of HMGB1 and TLR4 in the study group were significantly lower than those in thecontrol group (P < 0.05); after treatment, the levels of serum TNF-α and IL-6 in both groups decreased significantly when compared to those before treatment, and serum TNF-α and IL-6 levels in the study group were significantly lower than those in the control group (P < 0.05). The total effective rate was 75.47% in the control group and 94.34% in the study group, and there was a significant difference between two groups (P < 0.05); the total incidence of adverse reactions was 9.43% in the control group and 15.09%in the study group, and there was no significant difference between two groups (P>0.05). Pearson test showed that the expression levels of HMGB1 mRNAand TLR4 mRNA in mononuclear cells of peripheral blood and the serum protein contents of HMGB1 and TLR4 in ACI patients were positively correlated with NIHSS score (r=0.431, 0.443, 0.396, 0.375, P < 0.001); Spearman test showed that the expression levels of HMGB1 mRNA and TLR4 mRNA in mononuclear cells of peripheral blood and the serum protein contents of HMGB1 and TLR4 in ACI patients were negatively correlated with the total effective rate of treatment (r=-0.536, -0.481, -0.475, -0.506, P < 0.001).
    Conclusion Combination of Xueshuantong injection and intravenous thrombolysis with alteplase can effectively improve the neurological function of patients with ACI and reduce the level of inflammation in the body, and the therapeutic mechanism may be related to downregulation of the HMGB1/TLR4 signaling pathway.

     

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