目的 研究野黃芩苷對(duì)代謝相關(guān)脂肪性肝?。∕AFLD）大鼠的改善作用，并基于轉(zhuǎn)錄組學(xué)探討潛在機(jī)制。方法 將大鼠隨機(jī)分為對(duì)照組、模型組和野黃芩苷低、高劑量（50、100 mg·kg^-1）組，采用高脂飲食（HFD）飼喂16周誘導(dǎo)NAFLD大鼠模型，從第8周開始按分組對(duì)應(yīng)ig給藥，實(shí)驗(yàn)結(jié)束后測(cè)定體質(zhì)量及肝臟指數(shù)；采用試劑盒檢測(cè)血清丙氨酸氨基轉(zhuǎn)移酶（ALT）、天冬氨酸氨基轉(zhuǎn)移酶（AST）、總膽固醇（TC）和三酰甘油（TG）水平；采用蘇木素-伊紅（HE）、油紅O和Masson染色檢查肝臟病理變化；采用轉(zhuǎn)錄組學(xué)技術(shù)分析肝臟基因表達(dá)。結(jié)果 與對(duì)照組比較，模型組大鼠16周體質(zhì)量、肝臟質(zhì)量及肝臟指數(shù)明顯增加（P＜0.01）；血清中ALT、AST、TC和TG水平明顯升高（P＜0.01）；肝臟出現(xiàn)結(jié)構(gòu)性損傷、脂肪變性及氣球樣變等病理改變，紅色脂滴和藍(lán)色膠原纖維明顯變多。與模型組比較，野黃芩苷組大鼠16周體質(zhì)量、肝臟質(zhì)量及肝臟指數(shù)明顯降低（P＜0.05、0.01）；肝損傷及血脂相關(guān)指標(biāo)水平明顯恢復(fù)（P＜0.05、0.01）；肝臟病理改變趨于正常，紅色脂滴和藍(lán)色膠原纖維減少。轉(zhuǎn)錄組學(xué)結(jié)果顯示，對(duì)照組與模型組間有622個(gè)差異表達(dá)基因，模型組與野黃芩苷組間有579個(gè)差異表達(dá)基因，這其中有238個(gè)共有差異表達(dá)基因，并調(diào)控環(huán)磷酸鳥苷（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、晚期糖基化終末產(chǎn)物（AGE）-糖基化終末產(chǎn)物受體（RAGE）、鈣、胰島素抵抗和Hippo等信號(hào)通路。結(jié)論 野黃芩苷可能通過(guò)作用于肝臟238個(gè)基因，調(diào)控cGMP/PKG、PI3K/Akt、松弛素、AGE-RAGE、鈣、胰島素抵抗和Hippo等信號(hào)通路發(fā)揮對(duì)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.

江蘇省衛(wèi)生健康委科研項(xiàng)目（Z2022078）