围产期是奶牛感染性和代谢性疾病高发期，能量负平衡是该类疾病的病理学基础，肝脂代谢紊乱和氧化应激是其病理学特征。沉默信息调控因子2样蛋白3（SIRT3）是线粒体主要去乙酰化酶，在小鼠及人类已证实，SIRT3在能量负平衡条件下活化，是肝脂代谢及抗氧化防御的重要调节者，但SIRT3是否介入围产期奶牛肝脂代谢和抗氧化防御调节暂不明确。本项目以“SIRT3可通过调控关键酶活性从而发挥调节围产期奶牛肝脏能量代谢及抗氧化防御作用”为假设，在体测定围产期不同阶段奶牛肝脏SIRT3表达特征及线粒体蛋白乙酰化，调控SIRT3表达测定其对培养肝细胞脂代谢和抗氧化相关酶乙酰化水平及活性的影响，明确SIRT3对脂质代谢与抗氧化防御系统的调节作用，以期拓宽对围产期能量代谢调节的理解，并为揭示能量代谢障碍性疾病（如酮病、脂肪肝等）发病的分子机制提供启示，进而为探寻防治新靶标奠定理论基础。

The transition period (or perinatal period) is the time when most of contagious or metabolic disorders of dairy cows take place.Negative energy balance (NEB) is the common pathological basis,and hepatic lipid metabolism disturbances and oxidation stress are pathological features of those diseases.It is known that SIRT3 (silent mating-type information regulation 2 homolog 3),a major deacetylase in mitochondria,activates during NEB and plays a pivotal role in the regulation of lipid metabolism and antioxidant defense in mice and human.However,the role of SIRT3 in lipid metabolism and antioxidant defense in liver of dairy cows during transition period is not known so far.In order to test the hypothesis that SIRT3 regulates hepatic lipid metabolism and antioxidant defense during transition period via deacetylation of key enzymes,hepatic SIRT3 expression and acetylation of mitochondrial proteins during transition period are measured,and primary cultured cow hepatocytes modified by SIRT3 gene RNAi and overexpression are also tested for acetylation and activity of the key enzymes involved in lipid metabolism and antioxidant defense.The present project will make clear the effect of SIRT3 on hepatic lipid metabolism and antioxidant defense,which will further reveal new mechanism of energy regulation during transition period and offer new insight into the pathogenesis of common metabolic disorders like ketosis and fatty liver ect. in dairy cows so as to search new target or strategy for prevention and treatment for those diseases.