淫羊藿苷调控NLRP3炎症小体抗脑缺血再灌注机制
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1.贵州中医药大学;2.贵州中医药大学中药、民族药药理作用及作用机制研究中心

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Mechanism of Icariin regulating NLRP3 inflammasome against Cerebral Ischemia Reperfusion
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1.Guizhou University of Traditional Chinese Medicine;2.Research Center of Traditional Chinese Medicine and Ethnic Drug Pharmacological Activities and Mechanism,Guizhou University of TCM

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    摘要:

    目的:探讨淫羊藿苷治疗大鼠脑缺血再灌注损伤的作用机制。 方法:采用线栓法制备局灶性脑缺血再灌注大鼠模型。术后24 h将大鼠随机分为假手术组,模型组,丁苯酞组(70 mg穔g-1),淫羊藿苷高、中、低剂量组(80、40、20 mg穔g-1),灌胃相应药物10 mL穔g-1,每天给药一次,连续给药13 d。末次给药1 h后进行神经功能评分,苏木素-伊红(HE)染色法对大鼠大脑皮层进行病理学观察,免疫组化法测定大鼠大脑皮层白介素-1β(IL-1β)、白介素-18(IL-18)表达,蛋白印迹免疫法(Western blot)测定大鼠大脑皮层NOD 样受体热蛋白结构域 3(NLRP3)、相关斑点样蛋白(ASC)、半胱氨酸天冬氨酸蛋白水解酶-1(Caspase-1)蛋白表达。 结果:与假手术组比较,模型组大鼠神经功能评分显著增加;缺血周围区大脑皮层可见神经元不同程度坏死或胶质细胞增生,完整神经元数量显著减少;IL-1β、IL-18阳性细胞表达明显升高;NLRP3、ASC、Caspase-1蛋白表达显著增加(P<0.01,P<0.05)。经淫羊藿苷治疗后,大鼠神经功能评分明显降低;缺血周围区神经元坏死程度明显减轻,完整神经元数量显著增加;IL-1β、IL-18阳性细胞表达明显降低;NLRP3、ASC、caspase-1蛋白表达量显著下降(P<0.01,P<0.05)。 结论:淫羊藿苷治疗脑缺血再灌注损伤可能与调控NLRP3炎症小体有关。

    Abstract:

    Objective: To investigate the therapeutic effect of Icariin on cerebral ischemia reperfusion injury in rats. Methods: The rat model of focal cerebral ischemia reperfusion was established by the method of thread bolt. After 24 hours,rats were randomly divided into sham operation group,model group,Butylphthalide group(70 mg穔g-1),and high,medium and low dose groups (80、40、20 mg穔g-1) of Icariin. The volume of gastric administration was 10 mL穔g-1 once a day for 13 d. The changes in neurological deficit symptoms of rats were detected by neurological function score,while the pathological damage of cerebral cortex were detected by HE,the expression changes of IL-1β and IL-18 protein were detected by Immunohistochemistry,the protein expressions of NLRP3,ASC and Caspase-1 in cerebral cortex were detected by Western blot. Results: Compared with the sham operation group,the neurological score of the model group increased. The pathological results showed that neurons necrosis or glial cell proliferation in different degrees could be seen in the marginal area of each group. The contents of IL-18 and IL-1β protein in the brain tissue of the model group increased significantly,and the expressions of NLRP3,ASC and Caspase-1 protein in the brain tissue of the model group increased significantly (P < 0.01, P < 0.05). After Icariin treatment,compared with the model group,the neurological function score of the treatment group was improved. The pathological results showed that the degree of neuronal necrosis was significantly reduced,and the contents of IL-1β and IL-18 protein in the brain were significantly reduced.;The expression of NLRP3,ASC and Caspase-1 protein in rat cerebral cortex decreased significantly (P < 0.01, P < 0.05). Conclusions: Icariin in the treatment of cerebral ischemia reperfusion injury may be related to regulation NLRP3 inflammasome.

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  • 收稿日期:2023-05-23
  • 最后修改日期:2024-01-02
  • 录用日期:2024-01-15
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