目的 比较四氢姜黄素（THC）和姜黄素（CUR）对2型糖尿病（T2DM）心肌损伤的保护作用及机制差异。 方法 采用高脂饮食联合低剂量链脲佐菌素构建小鼠T2DM模型，随机分为4组：正常组（N组）、模型组（T2DM组）、CUR膳食干预组（T2DM+CUR组）和THC膳食干预组（T2DM+THC组），造模同时给予相应膳食补充（800 mg/kg饲料）。通过HE、Masson、PAS染色观察心肌组织形态、纤维化及糖原沉积；比色法检测氧化应激指标及血浆心肌损伤标志物乳酸脱氢酶（LDH）、心肌肌钙蛋白I（cTnI）；利用蛋白质组学筛选差异表达蛋白；Western blot验证通路相关蛋白的表达水平。 结果 与T2DM组相比，THC和CUR均能明显改善心肌细胞排列紊乱、减轻间质纤维化（P 0.01）和糖原沉积（P 0.05），降低血浆LDH、cTnI水平（P ＜ 0.05）；降低心肌组织丙二醛（MDA）水平（P 0.001），升高总抗氧化能力（T-AOC）（P 0.01）、超氧化物歧化酶（SOD）（P 0.05）、谷胱甘肽（GSH）活性（T2DM+THC组 vs. T2DM组， P 0.01），且T2DM+THC组的改善效果均优于T2DM+CUR组。同时，相关性分析显示小鼠空腹血糖水平与心肌损伤标志物LDH、cTnI含量呈显著正相关（P 0.001），提示血糖改善与心肌保护效应密切相关。机制上，蛋白质组学结合Western blot验证显示，THC比CUR更显著地抑制Hippo通路中STK3-LATS1轴的过度活化，具体表现为T2DM诱导的STK3与LATS1磷酸化水平显著下调（P ＜ 0.001）。 结论 THC可能通过抑制Hippo信号通路发挥改善T2DM小鼠心肌损伤的作用，其保护作用优于CUR，具备作为防治T2DM心肌损伤的天然膳食补充剂的潜力。

Objective This study compared the protective effects of curcumin （CUR） and Tetrahydrocurcumin （THC） against T2DM-related myocardial injury and delved into the differences in their mechanisms. Methods A mouse model of Type 2 diabetes mellitus （T2DM） was established by using a high-fat diet in combination with low-dose streptozotocin. The mice were randomly divided into four groups： the normal control group， the model group， the CUR dietary intervention group （800 mg/kg diet）， and the THC dietary intervention group （800 mg/kg diet）. Dietary supplements were administered concurrently with model induction. Myocardial morphology， fibrosis， and glycogen deposition were evaluated through hematoxylin and eosin （HE）， Masson， and periodic acid-Schiff （PAS） staining. Oxidative stress indicators and plasma cardiac injury markers， such as lactate dehydrogenase （LDH） and cardiac troponin I （cTnI）， were measured via colorimetric assays. Differentially expressed proteins were screened by proteomics， and the expression levels of pathway-related proteins were verified by Western blotting. Results Compared with the model group， both THC and CUR significantly alleviated myocardial disarray， diminished interstitial fibrosis （P 0.01） and glycogen deposition （P 0.05）， and decreased plasma levels of LDH and cTnI （P 0.05）. Moreover， they reduced myocardial malondialdehyde （MDA） levels （P 0.001） and enhanced total antioxidant capacity （T-AOC） （P 0.01）， superoxide dismutase （SOD） （P 0.05）， and glutathione （GSH） activities （T2DM+THC vs. T2DM， P 0.01）. Notably， THC exhibited more pronounced improvement than CUR across all these parameters. Correlation analysis indicated a significant positive correlation between fasting blood glucose levels and the cardiac injury markers LDH and cTnI， implying that the improvement of glycemic control is closely related to myocardial protection （P 0.001）. Mechanistically， proteomics combined with Western blot validation showed that THC more effectively inhibited the over-activation of the STK3-LATS1 axis in the Hippo pathway compared with CUR， as manifested by a remarkable down-regulation of the phosphorylation levels of STK3 and LATS1 induced by T2DM （P 0.001）. Conclusion THC may alleviate myocardial injury in T2DM mice by inhibiting the Hippo signaling pathway. It exhibits more potent cardioprotective effects than CUR， and therefore has the potential to serve as a natural dietary supplement for the prevention and treatment of T2DM-related myocardial injury.