二硫化碳对孕鼠胚胎和子宫组织基质金属蛋白酶-2和基质金属蛋白酶-9表达水平的影响

Effect of carbon disulfide on expression of matrix metalloproteinase-2 and metalloproteinase-9 in embryo and uterus of pregnant mice

目的 观察二硫化碳（CS2）对孕鼠胚胎和子宫组织中基质金属蛋白酶（MMP）-2、MMP-9表达水平的影响,探讨CS2致胚胎毒性作用机制.方法 昆明种小鼠随机分为对照组、卵泡发育期染毒组、胚胎植入早期染毒组、胚胎植入晚期染毒组,染毒组分别在卵泡发育期、胚胎植入早期、胚胎植入晚期腹腔注射631.4 mg/kg CS2,1次/d,连续2 d.孕第9天检查胚胎植入和发育情况,应用明胶酶谱法检测胚胎和子宫组织中MMP-2、MMP-9表达水平.结果 与对照组（30.700±5.599）比较,植入晚期染毒组胚胎植入数（16.000±12.166）明显减少,差异有统计学意义（P＜0.05）.染毒后胚胎组织中MMP-2、MMP-9表达均降低,其中植入晚期染毒组MMP-2、MMP-9分别为0.6837±0.0929、0.7309±0.0822,卵泡发育期染毒组分别为0.6222±0.0997、0.7520±0.1068,与对照组（分别为1.0000±0.0710、1.0000±0.0413）比较,差异均有统计学意义（P＜0.01）;植入晚期染毒组孕鼠子宫组织中MMP-2（1.3153±0.3032）、MMP-9（5.0210±4.0307）表达水平较对照组（分别为1.0000±0.1771、1.0000±0.0996）明显升高,差异有统计学意义（P＜0.01）.结论 胚胎植入晚期暴露CS2后胚胎毒作用明显,胚胎和子宫组织中MMP-2、MMP-9表达水平异常可能是CS2致胚胎毒性的重要机制之一.

Objective To observe the effect of carbon disulfide（CS2）on the expression of matrix metalloproteinase（MMP）-2, MMP-9 in mouse embryo and utems tissues and to explore the mechanism of embryo toxicity induced by CS2.Methods At the phases of follicular development and embryonic implantation which was subdivided into early-implantation phase and late-implantation phase, mice were intraperitoneally exposed to CS2（the dosage was 631.4 mg/kg, and the volume was 0.1ml/10 g body weight）for 2 consecutive days.All indicators were got at the ninth day in gestation, and the expression of MMP-2 and MMP-9 in embryo and uterus tissues was analyzed by gelatin zymography.Results The number of implanted embryos significantly decreased after exposure at late-implantation phase（16.000±12.166）compared with those of the control （30.700±5.599, P＜0.05）.Expression of MMP-2 and MMP-9 in embryos declined obviously at the three reproductive phases（P＜0.01）, and the levels of MMP-2 and MMP-9 expression in embryos at the phases of late-implantation phase（0.6837 ±0.0929,0.7309±0.0822）and follicular development（0.6222 ±0.0997,0.7520±0.1068）were much lower than those of the control（1.0000±0.0710, 1.0000±0.0413,P＜0.01）.Expression of MMP-2 and MMP-9 in uterus significantly increased at the phase of late-implantation（1.3153 ±0.3032,5.0210±4.0307）compared with those of the control（1.0000±0.177 1, 1.0000±0.0996, P＜0.0 1）.Conclusion Embryo toxicity of CS2 is more obvious at the phase of late-implantation.Exposure to CS2 disturbs expression of MMP-2 and MMP-9 in embryo and uterus tissues, which might be one of the important factors contributed to embryo toxicity induced by CS2.