文章摘要
基于NLRP3/Caspase-1细胞焦亡经典途径探讨菊花对脑缺血再灌注损伤大鼠的调控作用及机制
To investigate the regulatory effect and mechanism of chrysanthemum on cerebral ischemia-reperfusion injury in rats based on NLRP3/Caspase-1 cell pyrodeath classical pathway
投稿时间:2023-12-24  录用日期:2024-04-19
DOI:
中文关键词: 菊花  脑缺血再灌注损伤  细胞焦亡  抗炎
英文关键词: Chrysanthemum  Cerebral ischemia-reperfusion injury  Pyroptosis  anti-inflammatory
基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目)
作者单位邮编
李晓莹 黑龙江中医药大学 150006
陈阳燕 黑龙江中医药大学 150006
周明博 黑龙江中医药大学 150006
乌凯迪 黑龙江中医药大学 150006
蒋希成* 黑龙江中医药大学 150006
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中文摘要:
      目的:基于核苷酸结合域样受体蛋白3/半胱氨酸天冬氨酸蛋白水解酶-1(NLRP3/Caspase-1)信号通路介导的细胞焦亡经典途径探讨菊花对大鼠脑缺血再灌注损伤的影响作用及机制。方法:SD雄性大鼠分为假手术组,模型组,菊花低剂量组,菊花中剂量组和菊花高剂量组。造模前连续给药7天,造模成功24h后,评估大鼠神经功能缺损情况;检测大鼠脑组织含水量;HE染色观察大鼠脑组织形态学变化;ELISA法检测大鼠血清中白细胞介素-6(interleukin-6, IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白细胞介素-18(interleukin-18, IL-18)和白细胞介素-1β(interleukin-1β,IL-1β)含量;WesternBlot技术检测脑组织Caspase-1、GSDMD、NLRP3、IL-18、IL-1β的蛋白表达。结果:与假手术组相比,模型组大鼠神经功能病理性体征明显;脑组织含水量明显升高;脑组织结构呈筛网状,可见明显坏死灶。与模型组相比,菊花各剂量组大鼠状态有所改善,神经功能评分、脑组织含水量均有不同程度降低;细胞破裂溶解的数量、核固缩程度以及炎性细胞浸润情况都有所缓解。菊花各剂量组血清中IL-6、TNF-α、IL-18、IL-1β水平明显降低(P<0.01),Caspase-1、GSDMD、NLRP3、IL-18、IL-1β的蛋白表达水平明显降低(P<0.01)。结论:菊花可能通过抑制NLRP3/Caspase-1信号通路起到拮抗脑缺血再灌注的作用。
英文摘要:
      Objective: To investigate the effect and mechanism of chrysanthemum on cerebral ischemia-reperfusion injury in rats based on NLRP3/Caspase-1 signaling pathway mediated by nucleotide-binding domain-like receptor protein 3/ cysteine aspartate proteolytic enzyme-1 (NLRP3/Caspase-1). Methods: SD male rats were divided into sham operation group, model group, chrysanthemum low dose group, chrysanthemum medium dose group and chrysanthemum high dose group. The rats were given the drug continuously for 7 days before modeling, and the neurological deficits were evaluated after 24 hours of successful modeling. The water content of rat brain tissue was detected. The changes of brain histomorphology were observed by HE staining. Serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-18 (interleukin-18) were detected by ELISA method. IL-18) and interleukin-1β (interleukin-1β) content; The protein expressions of Caspase-1, GSDMD, NLRP3, IL-18 and IL-1β in brain tissue were detected by WesternBlot. Results: Compared with sham operation group, the pathological signs of neural function were obvious in model group. The water content of brain tissue increased significantly. The structure of the brain tissue was screened, with obvious necrotic foci. Compared with the model group, the state of rats in each dose group was improved, and the score of nerve function and water content of brain tissue were decreased to different degrees. The number of cell ruptures and lyses, the degree of nucleopytosis, and the inflammatory cell infiltration were all alleviated. Serum levels of IL-6, TNF-α, IL-18 and IL-1β were significantly decreased in each dose group (P<0.01), and protein expression levels of Caspase-1, GSDMD, NLRP3, IL-18 and IL-1β were significantly decreased (P<0.01). Conclusion: Chrysanthemum may play an antagonistic role in cerebral ischemia-reperfusion by inhibiting NLRP3/Caspase-1 signaling pathway.
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