雌二醇对Th1细胞极化与肝纤维化形成的影响

Effects of estradiol on Th1 cell polarization and liver fibrosis

目的探讨雌二醇(E2)对Th1细胞极化以及与肝纤维化发生的影响。方法根据E2水平将47例肝纤维化患者分为A组(E2增高组)19例和B组(E2正常组)28例,阴性对照作为C组(正常人)30例。应用流式细胞术检测T细胞亚群,化学发光法检测透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原氨基末端肽(PⅢP)和Ⅳ型胶原(CⅣ);ELISA法检测干扰素-γ(IFN-γ)、白介素-2(IL-2)、白介素-4(IL-4)和白介素-10(IL-10),比较A、B组之间以及与C组的差异。结果 A组E2高于C组和B组(P<0.001)。A组HA、LN、PⅢP、CⅣ均高于C组(P<0.001,P=0.001,P=0.006,P<0.001),B组HA、LN、PⅢP、CⅣ也高于C组(均为P<0.001);A组PⅢP高于B组(P=0.045)。A组CD3+T细胞低于C组和B组(P<0.001,P=0.001),CD4+T细胞也低于C组和B组(P<0.001,P=0.024),B组CD3+、CD4+T细胞低于C组(P=0.002,P<0.001);A组、B组CD8+T细胞高于C组(P=0.001,P=0.012)。A组IFN-γ高于C组和B组(均为P<0.001),IL-2也高于C组和B组(P<0.001,P=0.003),B组高于C组(P=0.001,P=0.012);A组IL-4低于C组和B组(P=0.002,P=0.016),IL-10也低于C组和B组(P<0.001,P=0.012)。结论高E2在延缓肝纤维化形成的同时也通过Th1细胞极化影响着机体的免疫功能,加速了肝纤维化的发展,E2在肝纤维化的形成过程中扮演了双重角色。

Objective To explore the effects of estradiol（ E2） on Th1 cell polarization and liver fibrosis. Methods A total of 47 patients with liver fibrosis were divided into 2 groups according to the level of E2： group A（ elevated E2 level,n = 19） and group B（ normal E2 level,n = 28）. Another 30 healthy people were enrolled as the negative controls（ group C）. The T lymphocyte subsets were measured with flowcytometry. The levels of hyaluronic acid（ HA）,laminin（ LN）,procollagen type Ⅲ amino-terminal peptide（ PⅢP） and type IV collagen（ CⅣ） were detected with chemiluminescence. The levels of IFN-γ,IL-2,IL-4 and IL-10 were measured with ELISIA assay. Then the parameters of the three groups were compared. Results The E2 level was higher in group A than in group C and group B（ P〈0. 001）. The levels of HA,LN,PIIIP and C Ⅳ in group A were all higher than those in group C（ P〈0. 001,P =0. 001,P = 0. 006,P〈0. 001）,and the levels of these four parameters in group B were also higher than those in group C（ all P〈0. 001）. The level of PⅢP was higher in group A than in group B（ P = 0. 045）. The percentage of CD3＋T cells in group A was lower than that in group C and group B respectively（ P〈0. 001,P = 0. 001）,and the percentage of CD4＋T cells was also lower than that in group C and group B（ P〈0. 001,P = 0. 024）,while the percentages of CD3＋T cells and CD4＋T cells in group B were all lower than those in group C（ P = 0. 002,P〈0. 001）;The percentage of CD8＋T cells in both group A and group B was higher than that in group C（ P = 0. 001,P = 0. 012）.The level of IFN-γ in group A was higher than that in group C and group B（ both P〈0. 001）,and the level of IL-2was also higher than that in group C and group B（ P〈0. 001,P = 0. 003）,at the same time,the levels of these twoparameters in group B were all higher than those in group C（ P = 0. 001,P = 0. 012）. The level of IL-4 in group A was lower than that in group C and group B（ P = 0. 002,P = 0. 016）,and the level of IL-10 was also lower than that in group C and group B（ P〈0. 001,P = 0. 012）. Conclusion E2 played a dual role in the formation of liver fibrosis.Elevated level of E2 accelerated liver fibrosis,and affected the immune function via Th1 cell polarization.