基于T淋巴细胞表达的纤维化蛋白/微粒双向调节HSC功能研究柔肝冲剂抗肝纤维化作用机制

肝星状细胞（HSC）活化及胶原合成大于降解是肝纤维化（HF）核心环节。T淋巴细胞表达的纤维化蛋白（FBRS）促进HSC活化及其胶原合成，T淋巴细胞表达的微粒（MP）抑制HSC活化、促进基质金属蛋白酶（MMP）表达降解胶原。前期研究证实"柔肝冲剂"通过抑制胶原合成促进降解抗HF。本研究拟开展：①建立ConA肝纤维化小鼠模型，观察柔肝冲剂对肝脏内T淋巴细胞FBRS、MP表达、HSC活化的影响，并分析FBRS、MP与HSC活化的相关性；②T淋巴细胞株表达的FBRS对HSC活化及胶原合成的调节机制；③T淋巴细胞株表达的MP对HSC活化及胶原降解的调节机制；④柔肝冲剂对T淋巴细胞株分泌FBRS和MP的影响，从而调节HSC功能的机制。以期证实柔肝冲剂可通过抑制T淋巴细胞FBRS表达、促进MP表达，双向调节HSC活化，从而抑制胶原合成、促进胶原降解抗HF的作用机制，进一步明确中药抗HF的现代生物学机制。

Activation of hepatic stellate cell(HSC) and more collagen synthesis than degradation is the core link of hepatic fibrosis(HF). The fibrosin(FBRS) expressed by T lymphocytes can promote the activation of HSC and synthesis of collagen, and microparticle(MP)derived from T lymphocytes can inhibit the activation of HSC and promote the expression of MMPs and collagen degradation. Our previous studies showed that Rougan granule play some roles in anti-hepatic fibrosis through inhibiting the synthesis of collogen and promoting its degradation. The contents of this research are as follows:① ConA induced murine model for hepatic fibrosis is used in this study,and the effects of Rougan granule on the expressions of FBRS and MP by T lymphocytes in the liver and the activation of HSC are examined, and the correlation between FBRS and MP expressions and the activation of HSC is analyzed;② the mechanism of HSC activation and collagen synthesis regulated by FBRS expressed by T cell line ;③the mechanism of HSC activation and collagen degradation regulated by MP derived from T cell line;④ the effects of Rougan granule on the expressions of FBRS and MP by T cell line and the relevant regulation mechanism of HSC activation . This research will confirm that the mechanism of Rougan granule on anti-hepatic fibrosis is through inhibiting the FBRS expression and promoting the MP expression and the dual-directional regulational roles on HSC actviation, and inhibiting the collagen synthesis and promoting degradation. This study will in further elucidate the modern biological mechanimsm of Chinese herbs on anti-hepatic fibrosis.