目的  探讨汉黄芩素（Wog）对乙型肝炎大鼠肝脏组织纤维化的影响及其调控Hippo-Yes相关蛋白（YAP）/含PDZ结合基序的转录共激活因子（TAZ）信号通路的机制。方法  大鼠随机分为正常对照（NC）组，模型（Mod）组、Wog低、中和高剂量组（Wog-L，10 mg/kg，Wog-M，20 mg/kg，Wog-H，40 mg/kg）、Wog-H+Hippo抑制剂组（40 mg/kg Wog+7 mg/kg XMU-MP-1），每组12只；除NC组，其余组均利用乙型肝炎病毒（HBV）建立大鼠模型，每周1次，连续注射3周。ELISA试剂盒检测各组大鼠血清肝功能指标：天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、谷氨酰转肽酶（GGT）、乙型肝炎E抗原（HBeAg）、乙型肝炎病毒表面抗原（HBsAg）和炎性因子转化生长因子β（TGF-β)、血小板衍生生长因子（PDGF）；肝纤维化指标：Ⅳ型胶原（Col-Ⅳ）、透明质酸（HA）、Ⅲ型前胶原肽（PⅢP）和层粘连蛋白（LN）；羟脯氨酸（Hyp）检测试剂盒检测Hyp水平；HE和Masson染色检测大鼠肝组织形态及纤维化；TUNEL法检测肝组织细胞凋亡；Western blotting检测肝组织α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原蛋白（Col-Ⅰ）、Hippo-YAP/TAZ信号通路相关蛋白表达；Real-time PCR检测肝组织YAP、TAZ mRNA表达。结果 与NC组相比，Mod组大鼠肝组织中细胞肿胀、排列异常且胶原纤维增生，肝纤维化明显，血清AST、GGT、ALT、HBeAg、HBsAg、TGF-β、PDGF、Col-Ⅳ、PⅢP、LN、HA及肝组织中胶原纤维沉积比例、Hyp水平、α-SMA、Col-Ⅰ蛋白表达和细胞凋亡率等显著升高（P＜0.05），YAP、TAZ蛋白和mRNA水平升高（P＜0.05）；与Mod组相比，Wog各剂量组大鼠的肝组织损伤减轻，血清肝功能相关指标及肝组织中胶原纤维沉积比例、Hyp水平、α-SMA、Col-Ⅰ蛋白表达和细胞凋亡率等显著降低（P＜0.05），YAP、TAZ蛋白和mRNA表达水平降低（P＜0.05）；与Wog-H组比较，加抑制剂组肝组织纤维化损伤明显加重（P＜0.05）。结论  Wog可能通过调控Hippo-YAP/TAZ信号通路活性，减轻乙型肝炎大鼠肝组织纤维化。

Objective  To investigate the effect of wogonin (Wog) on liver fibrosis in rats with hepatitis B and the mechanism of regulating Hippo-Yes-associated protein (YAP) / transcriptional coactivator with PDZ-binding motif (TAZ) signaling pathway. Methods  Rats were randomly grouped into normal control (NC) group, model group（Mod）, low-dose Wog group (Wog-L 10 mg/kg), medium-dose Wog group (Wog-M 20 mg/kg), high-dose Wog group (Wog-H 40 mg/kg), and Wog-H+Hippo inhibitor group (40 mg/kg Wog+7 mg/kg XMU-MP-1), each with 12 rats. Except for the NC group, rat model was established using hepatitis B virus (HBV) in other groups, injected once a week for three consecutive weeks. ELISA assay was used to detect serum liver function indicators, aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), hepatitis Be antigen (HBeAg), hepatitis B virus surface antigen (HBsAg), and inflammatory factors, transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), and liver fibrosis indicators, type Ⅳ collagen (Col-Ⅳ), hyaluronic acid (HA), type Ⅲ procollagen peptide (PⅢP), and laminin (LN). Hydroxyproline (Hyp) detection kit for detecting Hyp levels. HE and Masson staining were used to detect the morphology and fibrosis of liver tissue. TUNEL method was used to detect cell apoptosis in liver tissue. Western blotting was used to estimate the expression of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col-Ⅰ), and proteins related to Hippo-YAP/TAZ signaling pathway. Real-time PCR was used to detect the mRNA expressions of YAP and TAZ in liver tissues. Results  Compared with the NC group, the model group showed swelling, abnormal arrangement of cells, and obvious collagen fiber proliferation in the liver tissue, the levels of serum AST, GGT, ALT, HBeAg, HBsAg, TGF-β, PDGF, Col-Ⅳ, PⅢP, LN, HA, and the proportion of collagen fiber deposition in liver tissues, as well as the levels of Hyp, α-SMA, Col-Ⅰ protein expression, and the apoptosis rate obviously increased (P<0.05), and the protein and mRNA expression levels of YAP and TAZ increased significantly(P<0.05). Compared with the model group, the liver tissue damage of rats in each dose Wog group was reduced, the levels of serum-related indicators, and the proportion of collagen fiber deposition in liver tissues, as well as the levels of Hyp, α-SMA, Col-Ⅰ protein expression, and the apoptosis rate, and the protein and mRNA expression levels of YAP and TAZ significantly reduced (P<0.05). Compared with the Wog-H group, the Wog-H+XMU-MP-1 group showed obvious liver fibrosis damage (P<0.05). Conclusion  Wog may alleviate liver fibrosis in rats with hepatitis B by regulating activity of the Hippo-YAP/TAZ pathway.