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摘要：目的 探讨二硫化碳（CS2）暴露对孕鼠卵巢黄体巨噬细胞极化和功能的影响，从免疫损伤角度解析巨噬细胞在CS2致胚胎植入障碍中的作用。方法 建立围植入期不同时间点暴露于CS2动物模型，3个染毒组分别于受孕第3（GD3）、4（GD4）和5（GD5）天经腹腔染毒CS2（0.4 LD50，631.4 mg/kg）1次，各组设立平行溶剂对照（等体积橄榄油）。各组动物染毒后于不同时间点设立连续观察终点，取卵巢组织进行HE染色、免疫组织化学染色及实时荧光定量PCR实验，检测孕鼠卵巢组织中巨噬细胞极化和功能改变。结果 ①卵巢黄体巨噬细胞极化平衡在CS2染毒后表现为M1型巨噬细胞为主导（M1>M2，如GD3染毒组GD4观察终点，t=10.000，P<0.001）后期转变为M2型巨噬细胞为主导（M1<M2，如GD5染毒组GD6 观察终点，F=10.235，P=0.003）；②TNF-α 和Vegfa的mRNA表达水平升高（如Vegfa在GD4染毒组GD7观察终点，F=6.801，P=0.007）；孕鼠卵巢黄体表现为血管扩张与充血以及结构改变（如GD4染毒组GD5观察终点的结构评价，F=8.638，P=0.019）；Cox2和Hif1-α的mRNA表达均呈先升高后下降的趋势（如Cox2在GD3染毒组GD5观察终点，F=6.184，P=0.035）。结论 围植入期CS2暴露致胚胎植入障碍的机制可能是卵巢黄体巨噬细胞极化平衡与功能改变，引发并加重卵巢黄体结构和功能受损。
Abstract: Objective To investigate the effect of carbon disulfide (CS2) exposure on the polarization and function of corpus luteum macrophages in pregnant rats and the role of macrophages in embryo implantation induced by CS2 from the perspective of immuno-injury. Methods CS2 animal models were established at different time points during peri-implantation period. Three exposure groups were intraperitoneally treated with CS2 (0.4 LD50, 631.4 mg) on GD3, GD4 and GD5, / kg) once, each group set up a parallel solvent control (equal volume of olive oil). The animals were sacrificed at different time points after the establishment of continuous observation of end points, ovarian tissue taken HE staining, immunohistochemical staining and real-time fluorescence quantitative PCR assay to detect macrophage polarization and functional changes in ovarian tissue of pregnant rats. Results ① The polarization of corpus luteum macrophages was dominated by M1 macrophages after CS2 exposure (M1 & gt; M2, as GD3 in GD3 end point, t = 10.000, P & lt; 0.001) (M1, M2, GD5, F = 10.235, P = 0.003); ② The mRNA expression of TNF-α and Vegfa increased (for example, the observation of GD in GD4 group by Vegfa (F = 8.638, P = 0.019). The levels of Cox2 and Hif1-Hs1 in endometriosis were significantly higher than those in the control group α mRNA expression increased first and then decreased (such as Cox2 in the GD3 treatment group GD5 end point, F = 6.184, P = 0.035). Conclusions The mechanism of embryo implantation disturbance caused by peri-implantation CS2 may be the polarization balance and function change of luteal corpus luteum macrophage, causing and aggravating the structure and function of corpus luteum.