HDAC8调控PPARγ在体外循环相关急性肾损伤后适应不良性修复中的作用及机制研究

体外循环患者常因缺血再灌注诱发急性肾损伤，即使进入恢复期后也常伴发肾损伤后适应不良性修复，进而导致肾慢性纤维化。申请人前期研究证实，HDAC8作为一种特殊的组蛋白去乙酰化酶能在慢性肾纤维化过程中，通过多条成纤维信号通路，影响纤维化进程。PPARγ是一种参与肾脏稳态维持的转录因子，其功能受多种表观遗传学，包括乙酰化在内的影响。有研究表明PPARγ乙酰化可以在慢性肾功能不全中起到保护作用，但就其能否影响急性肾损伤后适应不良修复仍为未知。本研究拟建立缺血再灌注致急性肾损伤后肾适应不良性修复模型，通过干预HDAC8及PPAR-γ的表达水平，观察HDAC8对PPARγ的调控作用及对肾上皮间充质转化及间质纤维化的影响，进而评价HDAC8作为潜在靶点对治疗体外循环患者急性肾损伤后适应不良修复的作用。

Acute kidney injury is the most common postoperative comorbidity in patients receiving cardiopulmonary bypass surgery. Patients often suffer maladaptive repair after the incomplete recovery of postoperative AKI and turn into chronic renal disease finally. Our previous research revealed that HDAC8, as a special histone deacetylase, can affect kidney fibrosis process by regulating several fibroblasts signaling pathway. PPARγ is a nuclear transcription factor involves in a wide range of physiological and pathological processes. Its function is affected by a variety of epigenetics, including acetylation. Studies showed that the acetylation of PPARγ can play a protective role in chronic renal fibrosis. However, whether it can affect the maladaptive repair after AKI is still unknown. This study intends to establish a renal maladaptive repair model after AKI. By adjusting the expression of HDAC8 and PPARγ, we try to explain the effect of HDAC8 on PPARγ and its influence on renal epithelial-mesenchymal transition and interstitial fibrosis. This study also evaluates the role of HDAC8 as a potential target for treating the maladaptive repair after AKI caused by cardiopulmonary bypass surgery.