糖尿病心肌病是糖尿病引起的最严重的并发症之一，也是糖尿病患者发生心力衰竭的病理基础。糖尿病性心肌肥厚作为糖尿病心肌病发生发展的初始机制，被视为逆转心室重构，防治糖尿病心肌病发生发展的关键环节。申请人前期在糖尿病心肌病患者和小鼠的心脏组织中均发现FBXO40的异常升高，并且前期研究已经证实在小鼠体内FBXO40能够通过PPARα正向调控糖尿病性心肌肥厚的发生，并且这一过程与心肌细胞的糖脂代谢异常密切相关，但具体调控机制尚不清楚。本研究在此基础上，利用沉默FBXO40或PPARα的高糖细胞模型，应用慢病毒转导、免疫共沉淀等技术，探索FBXO40在糖尿病诱发的心肌重构中的分子作用机制，期望揭示新的分子调控途径“FBXO40-PPARα-糖尿病心肌病”，为临床防治糖尿病心肌病提供新思路和新靶点。

Diabetic cardiomyopathy is one of the most serious complications caused by diabetes and is also the pathological basis for heart failure in diabetic patients. Diabetic cardiac hypertrophy, as the initial mechanism of the occurrence and development of diabetic cardiomyopathy, is regarded as a key link to reverse ventricular remodeling and prevent the occurrence and development of diabetic cardiomyopathy. Our previous studies have found adnormal elevation of FBXO40 in the heart tissues of both diabetic cardiomyopathy patients and mice, and confirmed FBXO40 can positively regulate the occurrence of diabetic cardiac hypertrophy through PPARα in mice, and this process is closely related to the glycolipid metabolism of cardiomyocytes, but the specific regulatory mechanism is not yet clear. On the basis of this, the molecular mechanism of FBXO40 in diabetes-induced cardiac remodeling will be demonstrated by using lentiviral transduction, co-immunoprecipitation, and other technologies in high glucose cell models with FBXO40 or PPARα silencing, expecting to reveal a new molecular regulatory pathway, "FBXO40-PPARα-diabetic cardiomyopathy ", and provide new ideas and new targets for the clinical prevention and treatment of diabetic cardiomyopathy.