The Role Of Fasudil In Treg Differentiation Of Autoimmune Hepatitis Mice

Objective:To investigate the effects of Fasudil on the differentiation of Treg in concanavalin (ConA)-induced experimental autoimmune hepatitis mice, discussing the effects and possible mechanism of RhoA signaling on experimental autoimmune hepatitis.Methods: Female mice were randomly assigned to three groups (N=8): control group (NS + NS), ConA group (NS + ConA), Fasudil pretreated group (Fasudil + ConA), and each mouse was intravenous injected twice, which were interval 15min. Then study the possible effect and mechanism of RhoA on ConA– induced experimental autoimmune hepatitis, assess the ratio of ALT,AST in blood, pathology of liver, and the changes of Treg in CD4~+ T cells in liver.Results: (1) In contrast to the control, the number of mononuclear cell and Treg in ConA and pretreated group increased significantly (p<0.05). (2) Compared to the control, AST,ALT were dramatically promoted in ConA group (P < 0.05), while pretreated group were markedly reversed. (3) In ConA group, lymphocytes which were localized next to the portal were aggregated; liver cells showed a wide range of ballooning degeneration, hepatic lobules were damaged and liver cells necrosis. While the pathology of liver in pretreated group displayed a much more mild alteration. (4) Treg /CD4~+ T in control group was (4.53±3.62)%, which were (8.49±2.80)%,(4.53±1.08)% in ConA and pretreated group (P < 0.05). Conclusions: 1. ConA-induced acute liver injury manifested as T cells in inflammatory cell infiltration. 2. Fasudil could inhibit the Rho/ROCK singal pathway through acting on the downstream protein, reducing the ConA-induced injury and maybe could ease the injury of immunological liver. 3. Treg involved in regulating immune liver injury through the Rho/ROCK.