Abstract: Objective　To detect the expression of transforming growth factor⁃β1 (TGF⁃β1), p38MAPK and bone morphogenetic protein⁃7 (BMP⁃7) protein in the liver specimens of patients with hepatic alveolar echinococcosis, and to investigate the potential role of TGF⁃β1, p38MAPK and BMP⁃7 protein in hepatic fibrosis caused by hepatic alveolar echinococcosis. Methods　A total of 20 patients with hepatic alveolar echinococcosis were enrolled as study subjects, and hepatic specimens were sampled from the sites within 0.5 cm (Group A) and 0.5 to 1.5 cm from hepatic alveolar echinococcosis lesions (Group B), while normal liver specimens sampled from the sites 2 cm and greater from hepatic alveolar echinococcosis lesions served as controls (Group C). The fibrosis of liver specimens was pathological examined using HE and Masson staining, and the expression of TGF⁃β1, p38MAPK and BMP⁃7 protein was quantified in liver tissues using Western blotting. The associations of TGF⁃β1, p38MAPK and BMP⁃7 protein expression with hepatic fibrosis were assessed. Results　HE staining showed the malaligned structure of hepatocytes and destruction of the structure of hepatic lobules at various degrees in liver specimens in groups A and B, with hepatocyte degeneration, atrophy and necrosis, hyperplasia of fibrous tissues and eosinophilic granulocyte infiltration seen, while no abnormal pathological alterations of liver tissues, normal hepatocyte structure and morphology and uniform size, no malaligned structure of hepatocytes, clear structure of hepatic lobules, no or mild hepatocyte degeneration or necrosis, and no eosinophilic granulocyte infiltration were seen in Group C. Masson staining showed that there was hyperplasia of multiple fibrous connective tissues in the liver portal areas in groups A and B, with fibrosis seen in hepatic lobules, while no obvious pathological changes were seen in Group C. There were significant differences seen in TGF⁃β1 (P < 0.001), p38MAPK (P < 0.01) and BMP⁃7 protein (P < 0.05) expression in liver tissues in groups A, B and C, and higher TGF⁃β1, p38MAPK and BMP⁃7 protein expression was quantified in groups A and B than in Group C (all P values < 0.05), while greater TGF⁃β1, p38MAPK and BMP⁃7 protein expression was detected in Group B than in Group C (all P values < 0.05). The expression of TGF⁃β1, p38MAPK and BMP⁃7 protein correlated positively with the severity of hepatic fibrosis (r = 0.866, 0.702 and 0.801, all P values < 0.05), and there were significant differences in TGF⁃β1 (F = 72.580, P < 0.01), p38MAPK ([χ2] = 31.705, P < 0.01) and BMP⁃7 protein expression ([χ2] = 48.388, P < 0.01) among liver tissues with different degrees of fibrosis. The TGF⁃β1 protein expression correlated positively with p38MAPK and BMP⁃7 protein expression (r = 0.607 and 0.702, both P values < 0.001), and the BMP⁃7 protein expression also correlated positively with p38MAPK protein expression (r = 0.456, P < 0.001). Conclusion　The interaction among TGF⁃β1, p38MAPK and BMP⁃7 jointly participates in the development of hepatic fibrosis induced hepatic alveolar echinococcosis.

Key words: Hepatic alveolar echinococcosis, Hepatic fibrosis, p38MAPK, BMP7, TGF?β1

摘要： 目的　检测肝多房棘球蚴病患者肝组织中转化生长因子⁃β1（transforming growth factor⁃β1, TGF⁃β1）、p38MAPK及骨形态发生蛋白⁃7（bone morphogenetic protein⁃7, BMP⁃7）表达水平，探讨其在肝多房棘球蚴病肝纤维化中的潜在作用。方法　以20例肝多房棘球蚴病患者为研究对象，分别采集距肝脏病灶0.5 cm内（A组）、距肝脏病灶0.5～1.5 cm（B组）肝组织及距肝脏病灶2 cm及以上的正常肝组织（C组）。肝组织标本分别行HE和Masson染色观察纤维化病理变化，采用Western blotting检测肝组织中TGF⁃β1、p38MAPK及BMP⁃7蛋白表达水平，分析TGF⁃β1、p38MAPK及BMP⁃7蛋白表达与肝纤维化的相关性。结果　HE染色结果显示，A组和B组肝组织中肝细胞结构排列紊乱、肝小叶结构有不同程度破坏，可见不同程度肝细胞变性、萎缩、坏死及纤维组织增生，并有嗜酸性粒细胞浸润；C组肝组织无异常病理改变，肝细胞结构形态正常、大小均匀，未见明显排列紊乱，肝小叶结构清晰，无或轻度细胞变性、坏死及炎性细胞浸润。Masson染色结果显示，A组和B组肝组织可见汇管区较多纤维结缔组织增生，出现不同程度小叶内纤维化；C组肝组织无明显异常病理改变。A、B、C组肝组织中TGF⁃β1（P < 0.001）、p38MAPK（P < 0.01）及BMP⁃7蛋白（P < 0.05）表达水平差异均有统计学意义，A组和B组TGF⁃β1、p38MAPK及BMP⁃7蛋白表达水平均显著高于C组（P均< 0.05），B组TGF⁃β1、p38MAPK及BMP⁃7蛋白表达水平亦显著高于C组（P均< 0.05）。TGF⁃β1、p38MAPK及BMP⁃7蛋白表达水平均与肝纤维化程度呈正相关（r = 0.866、0.702、0.801，P均< 0.05），不同纤维化程度肝组织中TGF⁃β1（F = 72.580，P < 0.01）、p38MAPK（[χ2] = 31.705，P < 0.01）及BMP⁃7蛋白（[χ2] = 48.388，P < 0.01）表达水平差异均有统计学意义。TGF⁃β1蛋白与p38MAPK、BMP⁃7蛋白表达水平均呈显著正相关（r = 0.607、0.702，P均 < 0.001），BMP⁃7与p38MAPK蛋白表达水平亦呈显著正相关（r = 0.456，P < 0.001）。结论　TGF⁃β1、p38MAPK和BMP⁃7蛋白通过相互作用、共同介导了肝多房棘球蚴病肝纤维化发生。 　

关键词: 肝多房棘球蚴病, 肝纤维化, p38MAPK, BMP7, TGF?β1