目的 基于 KLF16/PPAR-α 信号通路探讨参苓白术散对代谢相关脂肪性肝病（MAFLD）小鼠肝脏脂质代 谢的影响。方法 将 C57BL/6 小鼠随机分为正常组、模型组及参苓白术散低、中、高剂量组（2.685、5.369、 10.738 g·kg-1·d-1），每组 7 只。除正常组给予标准饲料外，其余各组小鼠均给予高脂饲料连续喂养 12 周，复 制 MAFLD 模型。造模结束后开始灌胃给药，每日 1 次，连续 5 周。测定小鼠体质量及肝脏系数；采用 HE 及 油红 O 染色观察小鼠肝脏组织病理变化；检测血清谷氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、甘 油三酯（TG）及总胆固醇（TC）水平；RT-qPCR 法检测肝组织中 PPAR-α、KLF16、FAS、SREBP-1c mRNA 表达 水平。结果 与正常组比较，模型组小鼠的体质量、肝质量及肝脏系数明显升高（P＜0.05 ，P＜0.01）；血清 TG、TC 、ALT、AST 水平显著升高（P＜0.001）；肝细胞胞质可见大量空泡，出现大量红染的脂滴，NAS 病理 评分及油红 O 染色 IOD 值显著升高（P＜0.05，P＜0.001）；肝组织中 PPAR-α、KLF16 mRNA 表达显著下调 （P＜0.01，P＜0.001），FAS、SREBP-1c mRNA 表达显著上调（P＜0.05，P＜0.001）。与模型组比较，参苓白术 散高剂量组小鼠的体质量、肝质量、肝脏系数明显降低（P＜0.05）；参苓白术散低、中、高剂量组小鼠的血清 TG、TC、ALT 水平显著降低（P＜0.05，P＜0.01，P＜0.001）；参苓白术散中、高剂量组小鼠的血清 AST 水平 显著降低（P＜0.01，P＜0.001）；各给药组小鼠肝组织病理变化有明显改善，肝细胞胞质内橘红色脂滴显著减 少，参苓白术散高剂量组的 NAS 病理评分及油红 O 染色 IOD 值显著降低（P＜0.05，P＜0.01）；参苓白术散低、 中、高剂量组小鼠肝组织中 PPAR-α、KLF16 mRNA 表达显著上调（P＜0.05，P＜0.01，P＜0.001），FAS、 SREBP-1c mRNA 表达显著下调（P＜0.05，P＜0.01，P＜0.001）。结论 参苓白术散对 MAFLD 小鼠的肝脏脂 质代谢有明显改善作用，其机制可能与转录调控核受体 KLF16/PPAR-α 信号通路有关。

Objective To investigate the effects of Shenling Baizhu San on hepatic lipid metabolism in mice with metabolic associated fatty liver disease （MAFLD） based on the KLF16/PPAR-α signaling pathway. Methods C57 BL/6 mice were randomly divided into normal group，model group and Shenling Baizhu San low-，medium- and high- dose groups （2.685，5.369，10.738 g·kg-1·d-1），with seven mice in each group. Except for the normal group， the mice in the other groups were given high-fat diet for 12 weeks to replicate the MAFLD model. After the modeling，intragastric administration was started once a day for five weeks. The body mass and liver coefficient of mice were measured. HE and oil red O staining were used to observe the pathological changes of liver tissue in mice. The levels of serum alanine aminotransferase （ALT），aspartate aminotransferase （AST），triglyceride （TG） and total cholesterol （TC） were detected. The mRNA expression levels of PPAR-α，KLF16，FAS and SREBP-1c in liver tissue were detected by RT-qPCR. Results Compared with the normal group，the body mass，liver mass and liver coefficient of mice in the model group were significantly increased （P＜0.05，P＜0.01）. The levels of serum TG，TC，ALT and AST were significantly increased （P＜0.001）. There were a large number of vacuoles in the cytoplasm of the liver tissue，and a large number of red-stained lipid droplets appeared in the cytoplasm. The NAS pathological score and oil red O staining IOD value were significantly increased （P＜0.05，P＜0.001）. The mRNA expressions of PPAR- α and KLF16 in liver tissue were significantly down-regulated （P＜0.01，P＜0.001），and the mRNA expressions of FAS and SREBP-1c was significantly up-regulated （P＜0.05，P＜0.001）. Compared with the model group，the body mass，liver mass and liver coefficient of mice in the high-dose group of Shenling Baizhu San were significantly decreased （P＜0.05）. The levels of serum TG， TC and ALT in the low- ， medium- and high- dose groups of Shenling Baizhu San were significantly decreased （P＜0.05，P＜0.01，P＜0.001）. The serum AST level of mice in the medium- and high- dose groups of Shenling Baizhu San was significantly decreased （P＜ 0.01，P＜0.001）. The pathological changes of liver tissue in each administration group were significantly improved， and the orange-red lipid droplets in the cytoplasm of hepatocytes were significantly reduced. The NAS pathological score and oil red O staining IOD value of the high-dose group of Shenling Baizhu San were significantly reduced （P＜0.05，P＜0.01）；the mRNA expressions of PPAR-α and KLF16 in liver tissue of mice in Shenling Baizhu San low-，medium- and high- dose groups were significantly up-regulated （P＜0.05，P＜0.01，P＜0.001），and the mRNA expressions of FAS and SREBP-1c were significantly down-regulated （P＜0.05， P＜0.01， P＜0.001）. Conclusion Shenling Baizhu San can significantly improve hepatic lipid metabolism in MAFLD mice， and its mechanism may be related to transcriptional regulation of nuclear receptor KLF16/PPAR-α signaling pathway.

R285.5

国家自然科学基金面上项目（82070891）；广州市科技局民生科技项目（202002020032）；广州市基础与应用基础研究项目（202201011501）