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目的:探讨mTOR/HIF-1α信号通路在布-加综合征(B-CS)肝纤维化中的作用机制。方法:雄性C57小鼠20只按随机数字表法分为假手术(Sham)组、假手术+雷帕霉素(Sham+Ra)组、B-CS组、B-CS+雷帕霉素(B-CS+Ra)组，每组均5只。于肝后段下腔静脉(IVC)部分结扎构建B-CS小鼠模型；Sham组未结扎IVC。Sham+Ra和B-CS+Ra组小鼠隔天腹腔注射雷帕霉素(2 mg/kg，5%DMSO溶液配制)，Sham组和B-CS组注射同等剂量5%DMSO溶液。6周后取材，部分肝脏组织用于制作石蜡切片进行苏木精-伊红、天狼星红染色观察病理变化，免疫组织化学染色检测肝组织中α-SMA、Fibrinogen的表达；新鲜肝脏组织提取蛋白和RNA，分别用Western-blot检测α-SMA、Fibrinogen、p-mTOR、mTOR、HIF-1α、CollagenⅠ、VEGF蛋白水平，实时荧光定量PCR检测mTOR、HIF-1α、VEGF mRNA水平。计量资料用均数±标准差(n ±n s)表示，组间的比较采用单因素ANOVA检验。n 结果:病理染色结果显示，B-CS组小鼠肝脏中央静脉周围及肝窦淤血严重，窦间隙增宽，胶原沉积增加，表明本研究成功建立小鼠B-CS肝纤维化模型。Sham组纤维化指标α-SMA、CollagenⅠ蛋白，mTOR通路相关指标p-mTOR、HIF-1α蛋白，微血栓指标Fibrinogen蛋白表达量分别为0.027±0.012、0.337±0.008、0.138±0.024、0.296±0.113、0.733±0.192；B-CS组分别为0.986±0.001、0.927±0.055、0.936±0.044、1.693±0.443、1.612±0.068，两组相比差异有统计学意义(n P<0.05)。B-CS+Ra组表达量分别为0.707±0.078、0.311±0.024、0.332±0.094、0.254±0.117、0.569±0.075，与B-CS组相比，差异具有统计学意义(n P<0.05)。n 结论:mTOR/HIF-1α信号通路在小鼠B-CS肝纤维化中被显著激活，该通路可通过调节微血栓形成，参与肝纤维化发展。“,”Objective:To explore the mechanism of mTOR/HIF-1α signaling pathway in Budd-Chiari syndrome (B-CS) liver fibrosis.Methods:Twenty male C57 mice were randomly divided into Sham operation group (Sham), sham operation+ rapamycin (Sham+ Ra) group, B-CS group, B-CS+ rapamycin (B-CS+ Ra) Group, 5 in each group. The B-CS mouse model was constructed by partial ligation of the inferior vena cava(IVC) at the posterior segment of the liver; IVC was not ligated in the Sham group. Mice in Sham+ Ra and B-CS+ Ra groups were intraperitoneally injected with rapamycin (2 mg/kg, 5% DMSO solution preparation) every other day, Sham group and B-CS group were injected with the same dose of 5% DMSO solution.After 6 weeks, samples were taken, and part of the liver tissue was used to make paraffin sections for hematoxylin-eosin (HE) and Sirus Red staining to observe the pathological changes, and immunohistochemical staining to detect the expression of α-SMA and Fibrinogen in liver tissues; Protein and RNA were extracted from fresh liver tissue, and Western-blot was used to detect α-SMA, Fibrinogen, p-mTOR, mTOR, HIF-1α, Collagen I, and VEGF protein levels. Real-time fluorescent quantitative PCR was used to detect mTOR, HIF-1α, CollagenⅠ, VEGF mRNA levels.Measurement data were expressed as mean±standard deviation ( n ±n s), and the comparison between groups was performed by one-way ANOVA test.n Results:The results of pathological staining showed that in the B-CS group, there was severe congestion around the central vein of the liver and sinusoids, widening of the sinus space, and increased collagen deposition, indicating that this study successfully established a mouse B-CS liver fibrosis model. The expression levels of fibrosis indicators α-SMA and Collagen I protein, mTOR pathway related indicators p-mTOR and HIF-1α protein, and microthrombus indicator Fibrinogen protein in the Sham group were 0.027±0.012, 0.337±0.008, 0.138±0.024, 0.296±0.113, 0.733±0.192; B-CS group were 0.986±0.001, 0.927±0.055, 0.936±0.044, 1.693±0.443, 1.612±0.068, and the differences were statistically significant ( n P<0.05). The expression levels of B-CS+ Ra group were 0.707±0.078, 0.311±0.024, 0.332±0.094, 0.254±0.117, 0.569±0.075, which were statistically significant compared with B-CS group (n P<0.05).n Conclusions:The mTOR/HIF-1α signaling pathway is significantly activated in mouse B-CS liver fibrosis. This pathway may participate in the development of liver fibrosis by regulating microthrombosis.