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评估lapachol在缓解败血症引起的急性肺损伤方面的抗炎功效

Kavita Joshi¹, Vaishnavi Singh², Samit Chatterjee²

¹Department of Zoology, Govt. M.S. College for women, Bikaner 334001, Rajasthan, India.

|November 19, 2024

概括

拉帕霍尔在治疗败血症引起的急性肺损伤 (ALI) 中表现有前途,通过抑制JAK1通路,与药物托法西提尼布有类似的作用. 这种天然化合物为ALI提供了潜在的新治疗途径,ALI是一种目前没有确定的治疗方法的疾病.

科学领域:

药理学药理学是指药理学的学科.
免疫学免疫学免疫学
呼吸系统医学呼吸系统医学

背景情况:

败血症诱导的急性肺损伤 (ALI) 和急性呼吸困扰综合征 (ARDS) 是通过Janus Kinase (JAK) 途径的过度炎症导致的危及生命的疾病.
目前,对于ALI没有确定的药物治疗方法,这凸显了急需治疗干预的迫切需要.

研究的目的:

研究天然化合物lapachol,作为毒症诱导的ALI的潜在治疗剂.
评估lapachol在向JAK1通路的有效性,这是ALI中炎症的关键调解者.

主要方法:

进行了in-silico分析 (结合能量,RMSD,RMSF,H键图,lig图) 来评估lapachol与JAK1.1的结合.
在LPS诱导的ALI模型中使用了瑞士白色老鼠,用lapachol (20和40 mg/kg) 或tofacitinib (阳性对照) 治疗.
分析包括监测小鼠行为,体重,湿/干体重比,肺体重/体重比,支气管支气管洗 (BAL) 液体分析 (流动细胞计),组织学和髓氧化酶 (MPO) 测定.

主要成果:

在的研究支持了拉帕科尔与JAK1的结合,与托法西提尼布可比.
拉帕科尔和托法西替尼都显著降低了ALI标志物,包括肺体重/体重比,BAL细胞计数和粒细胞.
组织病理学和MPO测定表明,拉帕科尔,特别是40毫克/公斤,表现出与托法西提尼布相当的抗炎作用.

结论:

拉帕科尔通过抑制JAK1激酶域来表现出作为败血症诱导ALI的治疗剂的潜力.
在ALI模型中,lapachol的抗炎作用与JAK抑制剂托法西提尼布相当.
拉帕霍尔代表了进一步开发作为ALI治疗的有希望的候选人.

关键词:

急性肺损伤是什么?急性肺损伤是什么?在BAL流体中使用BAL流体.动态模拟的动态模拟组织病理学组织病理学詹姆斯1 1 在这里.拉帕科尔 (Lapachol) 是一个拉帕科尔.在MPO测试中使用MPO测试方法.分子对接是分子对接.托法西提尼布 (tofacitinib) 是一种可靠的药物.

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