巴西苏木素通过调节TLR4/NF-κB和NLRP3/Caspase-1通路改善急性肾损伤的作用机制研究

With an aging population, the incidence of AKI was keep in rising. And as the lack of the effective drugs and treatments, the case fatality rate of AKI was keep in a high level for several years. In the complex pathogenesis of AKI, inflammatory lesions occupy the central position, and has a close relationship with other damage mechanisms. TLR4 and NLRP3 as the main Pattern recognition receptors, which were in extracellular and intracellular respectively, has been the focus of AKI research, through TLR4/NF-κB and NLRP3/Caspase-1 pathway to release inflammatory factors, respectively. Our prophase study found out, Brazilin shown a significant kidney protection, firstly. It decrease the transcription of the NF-κB, reduce the inflammatory cytokines expression of TNF-α and IL-1β, shown an great effect of anti- inflammatory. But actually, targets and the mechanism of Brazilin on renal protection was still unclearly. Our team plans to use IR rats model of AKI and HK - 2 oxygen and sugar deprivation model, from multiple levels, such as animals, tissue, cell, protein to research the effect of Brazilin to TLR4 and NLRP3. And clarify Brazilin anesis IR injury by TLR4 / nf-kappa B and NLRP3 / Caspase-1. It is will be a great significance for further development of Brazilin to treatt/prevent AKI.

随着社会老龄化加剧，急性肾损伤（AKI）发生率逐年攀升，且由于治疗药物及策略的缺乏，其病死率一直居高不下。炎性损伤在AKI复杂的病理机制中占据中心位置。TLR4和NLRP3分别作为胞外、胞内的主要模式识别受体，是炎症反应的重要靶点，分别通过TLR4/NF-κB和NLRP3/Caspase-1通路释放炎性因子。本课题前期研究首次发现：活血化瘀中药苏木的主要药效成分Brazilin具有显著缓解IR性AKI的作用，抑制NF-κB转录，降低炎性因子表达，缓解抗炎性损伤，但其作用靶点与机制尚不明确。课题组拟运用IR大鼠AKI模型，和HK-2氧糖剥夺模型，从动物、组织、细胞、蛋白等多水平研究Brazilin对TLR4和NLRP3的作用，阐明Brazilin通过TLR4/NF-κB和NLRP3/Caspase-1缓解IR损伤的作用机制，为Brazilin进一步开发成为AKI防治药物提供理论基础。