转化生长因子β2对妊娠肝内胆汁淤积症患者胎盘组织分泌肿瘤坏死因子α及γ干扰素的影响

Influence of transfonning growth factor -β2 on production of tumor necrosis factor -α and interferon-γ from placenta of intrahepatic cholestasis of pregnancy

目的 探讨转化生长因子β2(TGF-β2)对妊娠肝内胆汁淤积症(ICP)患者胎盘组织分泌肿瘤坏死因子α(TNF-α)和γ干扰素的影响。方法 选取10例ICP患者(ICP组)和10例正常孕妇(对照组)的胎盘组织,通过体外培养后,采用酶联免疫吸附试验(ELISA)检测不同浓度TGF-β2[0浓度、低浓度(1μg/L)、高浓度(10μg/L)]对两组体外培养1、24、48 h的胎盘组织上清液中TNF—α和γ干扰素的水平。结果(1)胎盘组织培养1、24、48 h时,ICP组胎盘组织上清液中的TNF—α水平分别为(771±187)pg/g、(2490±575)pg/g、(3339±1106)pg/g,γ干扰素水平分别为(931 ±148)pg/g、(1888 ±545)Pg/g、(3027±667)Pg/g;对照组胎盘组织上清液中的TNF-α水平分别为(106±40)pg/g、(658±177)Pg/g、(1099+264)pg/g,γ干扰素水平分别为(404 ±155)Pg/g、(936 ±142)pg/g、(1386 ±378)Pg/g。ICP组TNF-α和γ干扰素水平均明显高于对照组,两组比较,差异有极显著性(P<0.001)。(2)不同浓度(0浓度、低浓度、高浓度)TGF-β2抑制ICP组胎盘组织分泌TNF—α[24 h时分别为(2490 ±575)pg/g、(1806±502)pg/g、(1231±238)Pg/g;48 h时分别为(3339±1106)pg/g、(2168±794)pg/g、(1047±183)pg/g]和γ干扰素[24 h时分别为(1888±545)pg/g、(1347±405)pg/g。

Objective To investigate the influence of transforming growth factor-β2(TGF-β2) on production of tumor necrosis factor -α (TNF-α) and interferon-γ (IFN-γ) from placenta of patients with intrahepatic cholestasis of pregnancy (ICP). Methods Villous explants from 10 ICP patients(ICP group) and 10 normal gravidae (control group) were cultured in vitro. The concentrations of TNF-α and IFN-γ in the culture medium were determined by enzyme linked immunoadsorbent assay ( ELISA) after incubation with different concentrations of TGF-β2 for 1,24 and 48 hours. Results (1) After cultured for 1,24 and 48 hours, TNF-α level in ICP group was (771 ± 187)pg/g, (2 490 ±575)pg/g,and (3339 ± 1106)pg/g, respectively, while IFN-γ level was (931 ± 148) pg/g, (1888 ± 545) pg/g, and (3027 ± 667) pg/g, respectively. All were significantly higher than those in the normal group (P <0. 001). (2) TGF-β2 could inhibit the release of above cytokines in a time- and dose-dependent manner;TNF-a level was(2490 ±575) pg/g,(1806 ±502) pg/g, and (1231 ±238)pg/g after 24 h,(3339 ± 1106)pg/g, (2168 ±794)pg/g,and (1047 ±183)pg/g after 48 h, respectively; IFN-γ level was (1888 ±545) pg/g,(l 347 ±405) pg/g,and (913±303) pg/gafter 24h, and (3027 ±667) pg/g, (2062 ±795) pg/g, and (1001 ± 301) pg/g after 48 h, respectively. Conclusion (1) The excessive production of TH1 type cytokines TNF-α and IFN-γ may involve in the pathogenesis of ICP; (2) TGF-β2 may exert immunoprotection effect through inhibiting the production of TNF-α and IFN-γ