Gprc5b通过NF-κB/NLRP3/Caspase-1通路诱导细胞焦亡对IgA肾病足细胞损伤的作用及通络保肾方的干预机制

足细胞损伤是导致IgA肾病(IgAN)蛋白尿和病程持续进展的关键因素，是近年来研究的热点。研究表明，NF-κB/NLRP3/Caspase-1通路介导的细胞焦亡是足细胞炎性损伤的后续重要病变。本课题前期研究证实基于足细胞损伤“瘀、浊”中医核心病机的“通络保肾方”对IgAN疗效显著，能减少蛋白尿和阻抑病情进展。因此我们假说该方可能通过新发现的足细胞促炎性受体Gprc5b抑制NF-κB/NLRP3/Caspase-1通路从而改善足细胞损伤。本研究通过制备IgAN大鼠模型及足细胞培养，应用qRT-PCR、Western blot、免疫组化、电镜等技术，观察足细胞损伤后不同时间点细胞焦亡Gprc5b、NF-κB、Caspase-1、IL-1β、IL-18、GSDMD-NT等基因的表达变化以及通络保肾方干预后对上述基因表达的影响，探讨该方改善足细胞损伤的机制，以期为IgAN的防治提供新靶点和新方法。

Podocyte injury is a key factor that leads to proteinuria and continuous progression in IgA nephropathy, and it has become a research hotspot in recent years. Studies had shown that NF-κB / NLRP3 / Caspase-1 signal pathway mediated pyroptosis which is an important follow-up lesion of podocyte inflammatory injury. The previous research of this study confirmed that "Tongluo Baoshen decoction ", which is based on the pathogenesis of "Blood stasis and Turbidity" of TCM, can reduce proteinuria and inhibit the progress of the disease. Therefore, we hypothesized that this recipe might improve podocyte injury by inhibiting the NF-κB / NLRP3 / Caspase-1 pathway via the newly discovered podocyte proinflammatory receptor Gprc5b. In this study, we will make a rat model of IgA nephropathy and culture the rat podocytes, also use these techniques of qRT-PCR, Western blot, Immunohistochemistry and Electron microscopy, then observe the mRNA expression of Gprc5b, NF-κB, Caspase-1, IL-1β, IL-18, GSDMD-NT at different time points after podocyte injury and the effect of "Tongluo Baoshen decoction" on those mRNA expression, in order to explore the recipe´s mechanism of improving podocyte injury, so as to provide a new target and method for the prevention and treatment of IgA nephropathy.