目的 研究野黄芩苷对代谢相关脂肪性肝病（MAFLD）大鼠的改善作用，并基于转录组学探讨潜在机制。方法 将大鼠随机分为对照组、模型组和野黄芩苷低、高剂量（50、100 mg·kg^-1）组，采用高脂饮食（HFD）饲喂16周诱导NAFLD大鼠模型，从第8周开始按分组对应ig给药，实验结束后测定体质量及肝脏指数；采用试剂盒检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆固醇（TC）和三酰甘油（TG）水平；采用苏木素-伊红（HE）、油红O和Masson染色检查肝脏病理变化；采用转录组学技术分析肝脏基因表达。结果 与对照组比较，模型组大鼠16周体质量、肝脏质量及肝脏指数明显增加（P＜0.01）；血清中ALT、AST、TC和TG水平明显升高（P＜0.01）；肝脏出现结构性损伤、脂肪变性及气球样变等病理改变，红色脂滴和蓝色胶原纤维明显变多。与模型组比较，野黄芩苷组大鼠16周体质量、肝脏质量及肝脏指数明显降低（P＜0.05、0.01）；肝损伤及血脂相关指标水平明显恢复（P＜0.05、0.01）；肝脏病理改变趋于正常，红色脂滴和蓝色胶原纤维减少。转录组学结果显示，对照组与模型组间有622个差异表达基因，模型组与野黄芩苷组间有579个差异表达基因，这其中有238个共有差异表达基因，并调控环磷酸鸟苷（cGMP）/蛋白激酶G（PKG）、磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）、松弛素、晚期糖基化终末产物（AGE）-糖基化终末产物受体（RAGE）、钙、胰岛素抵抗和Hippo等信号通路。结论 野黄芩苷可能通过作用于肝脏238个基因，调控cGMP/PKG、PI3K/Akt、松弛素、AGE-RAGE、钙、胰岛素抵抗和Hippo等信号通路发挥对NAFLD大鼠的改善作用。

Objective To investigate the effect of scutellarin on non-alcoholic fatty liver disease (NAFLD) rats and to explore the underlying mechanisms based on transcriptomics. Methods The rats were randomly divided into control group, model group and scutellarin low- and high- dose (50 and 100 mg·kg^-1) groups, and the NAFLD rat model was induced by high-fat diet (HFD) feeding for 16 weeks, and the drug was administered by gavage corresponding to the group from the 8th week, and liver tissues and serum were collected at the end of the experiment. The kits were used to detect the level of alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TC) and triglyceride (TG) levels. Hematoxylin-eosin (HE), oil red O and Masson staining were used to detect the pathological changes of rat liver. The gene expression of rat liver was analyzed by transcriptome technology. Results Compared with the control group, the body weight, liver weight and liver index of the model group rats at 16 weeks were significantly increased (P < 0.01), and serum levels of ALT, AST, TC and TG were significantly increased (P < 0.01). The pathological changes such as structural damage, steatosis and ballooning occurred in the liver, red lipid droplets and blue collagen fibers in the liver became significantly more abundant. Compared with model group, the body weight, liver weight and liver index at 16 weeks were significantly lower in the scutellarin groups (P < 0.05 and 0.01), the levels of liver injury and blood lipid-related indexes were significantly restored (P < 0.05 and 0.01), the pathological changes of liver tend to be normal, and red lipid droplets and blue collagen fibers in the liver were significantly reduced. The transcriptome results showed that there were 622 differentially expressed genes between the control and model groups and 579 differentially expressed genes between the model and scutellarin groups, of which 238 shared differentially expressed genes and regulated cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), relaxin, advanced glycosylation end products (AGE)-receptor of AGE (RAGE), calcium, insulin resistance, and Hippo signaling pathways. Conclusion Scutellarin may exert its ameliorative effects on NAFLD rats by acting on 238 genes in the liver to regulate signaling pathways such as cGMP/PKG, PI3K/Akt, relaxin, AGE-RAGE, calcium, insulin resistance and Hippo.

江苏省卫生健康委科研项目（Z2022078）