抑制MBD2通过下调Rac1和Pcbp2保护脓毒症AKI的机制研究

脓毒症所致急性肾损害（AKI）在AKI中占据重要地位，我们前期研究报道抑制MBD2能减轻万古霉素所致的AKI，但其对脓毒症AKI的作用及机制尚不清楚。因此，本项目拟采用LPS诱导的RPTC损伤模型及LPS和CLP诱导的AKI动物模型，探讨MBD2调控RPTC损伤的作用及机制。预实验构建LPS诱导的RPTC损伤模型，转染MBD2 siRNA后显著下降凋亡率、caspase活性、凋亡相关基因及炎症因子的表达。进一步基因芯片表达、Real time PCR和Western blot证明Rac1和Pcbp2表达显著下调。为此，本项目拟通过抑制MBD-2探讨LPS上调Rac1和Pcbp2的分子机制，并深入探讨Rac1和Pcbp2促进凋亡或炎症的分子机制，进而使用MBD2敲除小鼠使用LPS和CLP所致AKI模型揭示其肾保护的作用及机制，为抑制MBD2抗脓毒症AKI提供科学的理论依据和新的防治。

Sepsis is the leading cause of acute kidney injury, which is the top cause of acute kidney injury(AKI). Our previous studies demnonstrated that inhibition of MBD2 can alleviate VAN-induced AKI, however，the role and regulation mechanism of it in septic AKI remains unclear. Therefore,the vitro model was induced by LPS, the vivo model was produced by LPS and CLP, both of them were used to explore the effect and mechanism of MBD2 in this project. The vitro model was constructed by pre experiment. LPS treatment induced higher apoptosis rate, caspase activity, the expression of apoptosis related genes and inflammatory factors, which was markedly suppressed by MBD2 siRNA. The gene array analysis, Real time PCR and Western blot further showed that the expression of Rac1 and Pcbp2 was significantly downregulated. Therefore, this project aims to explore the molecular mechanism of LPS-induced the expression of Rac1 and Pcbp2 that suppressed by MBD2 siRNA, and then explore the molecular mechanism of promoting apoptosis or inflammation of Rac1 and Pcbp2, and then use MBD2 knockout mice, investigatel the renoprotection role and mechanism in septic AKI, it will provide a scientific theoretical basis and new therapeutic target for LPS and CLP-induced AKI.