阿替普酶联合红花提取物调节TLR4-NLRP3信号通路对大鼠急性脑梗塞的影响

doi:10.3969/j.issn.1006-6233.2023.09.04

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摘要 目的: 研究阿替普酶静脉溶栓联合红花提取物对急性脑梗塞的改善作用及潜在机制。方法: 30只SD大鼠,随机选取6只作为假手术组,其余大鼠均构建急性脑梗塞模型。模型构建成功后,随机将造模大鼠分为模型组、阿替普酶组(尾静脉注射阿替普酶5mg/kg)、红花提取物组(尾静脉注射4g/kg)、阿替普酶联合红花提取物组,每组6只。各给药组大鼠给予相应干预,假手术组和模型组大鼠注射等体积的无菌0.9%氯化钠溶液,连续7d。通过Zea Longa进行神经功能缺损评分;TTC染色评价梗死面积;HE染色观察组织病理变化;伊文思蓝(Evans blue)含量测定;TUNEL法检测各组细胞凋亡;qRT-PCR检测脑组织TLR4、NF-κB p65、NLRP3 mRNA表达;Western blotting分析脑组织MMP-2、MMP-9、Bax、Bcl-2、TLR4、NF-κB p65、p-NF-κB p65、NLRP3、caspase1、pro-IL-1β蛋白表达。结果: 与假手术组比较,模型组Zea Longa评分显著升高,梗死面积显著增加,EB含量、细胞凋亡率、MMP-2、MMP-9、Bax、TLR4、NF-κB p65、NLRP3、p-NF-κB p65、caspase1、pro-IL-1β蛋白表达及TLR4、NF-κB p65、NLRP3 mRNA表达显著升高,Bcl-2蛋白表达显著降低(P<0.05);与模型组比较,阿替普酶联合红花提取物组能显著降低Zea Longa评分及梗死面积,EB含量、细胞凋亡率、MMP-2、MMP-9、Bax、TLR4、NF-κB p65、NLRP3、p-NF-κB p65、caspase1、pro-IL-1β蛋白表达及TLR4、NF-κB p65、NLRP3 mRNA表达显著降低,Bcl-2蛋白表达显著升高(P<0.05)。结论: 阿替普酶静脉溶栓联合红花提取物对急性脑梗塞大鼠具有保护作用,其通过抑制TLR4-NLRP3信号通路及减少细胞凋亡,从而改善急性脑梗塞受损的神经功能,是潜在疗法。

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	刘明亮
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关键词 ：急性脑梗塞, 阿替普酶, 红花提取物, TLR4-NLRP3信号通路

Abstract：Objective: To study the ameliorative effect of intravenous thrombolysis with alteplase combined with safflower extract on acute cerebral infarction (ACI) and the potential mechanism. Methods: Among 30 SD rats, 6 were randomly selected as sham-operated group, and the rest were constructed as acute cerebral infarction model. After successful construction of the model, the modeled rats were randomly divided into model group, alteplase group (tail vein injection of alteplase 5 mg/kg), safflower extract group (tail vein intravenous 4 g/kg), and alteplase combined with safflower extract group, 6 rats in each group. Rats in each administration group were given the corresponding interventions, and rats in the sham-operated and model groups were injected with an equal volume of sterile 0.9% sodium chloride solution for 7 days. The neurological deficits were scored by Zea Longa; the infarct area was evaluated by TTC staining; histopathological changes were observed by HE staining; Evans blue content was determined; the apoptosis was detected by TUNEL method; TLR4, NF-κB p65, NLRP3 mRNA expression in brain tissue was detected by qRT-PCR; Western blotting analysis of protein expression of MMP-2, MMP-9, Bax, Bcl-2, TLR4, NF-κB p65, p-NF-κB p65, NLRP3, caspase1, pro-IL-1β in brain tissues. Results: Compared with the sham-operated group, the model group had significantly higher Zea Longa score, significantly increased infarct area, and EB content, apoptosis rate, MMP-2, MMP-9, Bax, TLR4, NF-κB p65, NLRP3, p-NF-κB p65, caspase1, pro-IL-1β protein expression and TLR4, NF-κB p65, NLRP3 mRNA expression were significantly higher and Bcl-2 protein expression was significantly lower (P<0.05). Compared with the model group, alteplase combined with safflower extract group could significantly reduce Zea Longa score and infarct area, EB content, apoptosis rate, MMP-2, MMP-9, Bax, TLR4, NF-κB p65, NLRP3, p-NF-κB p65, caspase1, pro-IL-1β protein expression and TLR4, NF-κB p65, NLRP3 mRNA expression was significantly decreased and Bcl-2 protein expression was significantly increased (P<0.05). Conclusion: Alteplase intravenous thrombolysis combined with safflower extract has a protective effect in rats with acute cerebral infarction, and it is a potential therapy to improve the impaired neurological function in acute cerebral infarction by inhibiting TLR4-NLRP3 signaling pathway and reducing apoptosis.

Key words： Acute cerebral infarction Alteplase Safflower extract TLR4-NLRP3 signaling pathway

基金资助:河北省中医药管理局科研课题,(编号:2022264)

引用本文:

刘明亮, 杨森林, 马超. 阿替普酶联合红花提取物调节TLR4-NLRP3信号通路对大鼠急性脑梗塞的影响[J]. 河北医学, 2023, 29(9): 1426-1431.
LIU Mingliang, YANG Senlin, MA Chao. Effects of Alteplase Combined with Safflower Extract on ACI in Rats through the Regulation of TLR4-NLRP3 Signaling Pathway. HeBei Med, 2023, 29(9): 1426-1431.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.09.04 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I9/1426

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