传统观点认为甲状腺功能紊乱时血脂异常是甲状腺激素（TH）造成的，但亚临床甲状腺功能减退时，促甲状腺素(TSH)升高，TH正常，依然可以出现血脂紊乱，易于发生动脉粥样硬化，是冠心病的独立危险因素。我们推测升高的TSH在血脂紊乱和动脉粥样硬化的发生中起重要作用。研究显示：细胞内游离胆固醇在酰基辅酶A：胆固醇脂酰转移酶（ACAT）的催化下，生成胆固醇酯，肝脏胆固醇酯的分泌率与冠状动脉粥样硬化的发生呈显著正相关。TSH在胆固醇酯化中是否发挥作用，国内外尚未有研究。我们的前期研究证实肝脏存在有生物活性的TSH受体，TSH可促进肝细胞ACAT2 的表达, 增加胆固醇酯的生成。在TSH受体敲除的小鼠中ACAT2表达明显减少。本研究拟通过体内（甲状腺摘除甲减大鼠模型、TSH受体敲除小鼠、TSH受体RNA干扰小鼠）与体外细胞水平探讨TSH在肝脏对ACAT2表达的影响及机制，揭示TSH致血脂紊乱的新作用。

The abnormality of thyroid hormone (TH) has been widely considered as the underlying mechanism for dyslipidemia in thyroid dysfunction. However, in certain diseases, such as subclinical hypothyroidism (SCH), in which TH levels are maintained at normal levels and only the TSH level is increased, evident elevations in an atherogenic lipid profile and ischemic heart disease are often observed in clinic. Apparently, dyslipidemia in SCH does not result solely from TH deficiency. TSH may play a direct regulatory role on lipid metabolism which has not been explored to date. Acyl-CoA cholesterol acyl transferase (ACAT) is an important enzyme in the formation of cholesteryl esters (CE) from cholesterol. Hepatocytic ACAT2 is a key cholesterol esterification enzyme necessary for the development of hypercholesterolemia. Moreover, CE in the liquid phase comprises a major fraction of the lipid-rich core of the plaque, and its abundance has been associated with plaque rupture and formation of atherothrombosis. No studies have evaluated whether there is a direct effect of TSH on the formation of cholesteryl esters. Our previous research has shown that thyrotropin receptor (TSHR) is present and functional in hepatocytes. Our preliminary study even demonstrated that TSH has a novel role in the promotion of ACAT2 expression that resulted in increased CE level. And the expression of ACAT2 reduced sharply in the TSHR knock-out mice. In the following study, we will explore the effect and mechanism of TSH on the expression of hepatocytic ACAT2. A series of in vivo and in vitro experiments will be performed to ensure the integrity of our theory. The results of our study may be a useful strategy for prevention and treatment of dyslipidemia and atherosclerosis.