环孢素A诱导妊娠失败模型孕鼠外周母-胎免疫耐受

目的探讨环孢素A(cyclosporin A,CsA)能否诱导妊娠失败模型CBA/J×DBA/2孕鼠外周母-胎免疫耐受。方法分别使用CBA/J×DBA/2及CBA/J×BALB/c作为妊娠失败模型和正常妊娠模型,CBA/J小鼠于妊娠第4天(着床期)腹腔注射不同剂量(0、5、10、15mg/kg)CsA,妊娠第9天和第14天时分别采用单向混合淋巴细胞反应分析孕鼠外周脾脏免疫细胞对父系抗原的增殖能力,并用RT-PCR分析细胞IL-2mRNA含量以研究脾脏细胞母-胎免疫耐受状态;妊娠第14天观察两组的胚胎吸收率。结果(1)于妊娠第4天腹腔注射5、10、15mg/kg CsA后,妊娠失败模型胚胎吸收率分别下降至2.86%、5.75%及11.24%,明显低于对照组(P<0.001,P<0.01,P<0.01);而对妊娠成功模型胚胎吸收率无显著性影响(P>0.05)。(2)混合淋巴细胞反应研究显示,于妊娠第4天腹腔注射CsA,可使妊娠第9、14天的妊娠失败模型孕鼠外周脾脏免疫细胞对父系抗原的增殖能力显著下降(P均<0.01);RT-PCR分析显示,孕鼠脾细胞受父系抗原刺激后IL-2转录显著下降(P均<0.01)。结论于孕早期腹腔注射CsA可诱导妊娠失败模型孕鼠外周免疫细胞对父系抗原的特异性免疫耐受,从而使自然流产模型孕鼠的妊娠结局达到正常妊娠水平,提示CsA可能成为治疗妊娠失败的有效药物。

Cyclosporin A induces peripheral maternal-fetal immumo-tolerance of the abortion-prone murine model

Objective To testify if cyclosporin A (CsA) induces peripheral maternal-fetal immuno-tolerance of the murine abortion-prone model. Methods CBA/J female mice were injected i.p by 0, 5, 10, 15 mg/kg CsA on day 4 of gestation respectively after they were mated to DBA/2 as a abortion-prone model or BALB/c male mice as a successful pregnancy model. The resorption rate was calculated on day 14 of gestation, immuno-tolerance and IL-2 mRNA level were checked by mixed lymphocyte reaction and RT-PCR on day of 9, 14 of gestation respectively. Results CsA administrated on day 4 of gestation significantly reduced the embryo resorption rate of the abortion-prone model, and induced a significantly lower proliferation response and IL-2 production by maternal splenic immuno-competent cells to paternal antigen as compared to the control group. Conclusion Administration of CsA on day 4 of gestation, the duration of peri-implantation, could induce paternal immuno-tolerance, which lead to the embryo resorption rateof the abortion-prone model to normal level. We conclude that CsA is a potential medicine for the treatment of pregnancy loss.