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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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

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	LIU Mingliang
	YANG Senlin
	MA Chao

Cite this article:

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[J]. HeBei Med, 2023, 29(9): 1426-1431.

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

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