p38丝裂原活化蛋白激酶特异性抑制剂对小鼠早胚发育及植入的影响

目的观察p38丝裂原活化蛋白激酶（p38MAPK）特异性抑制剂SB203580对小鼠早胚发育及植入的影响。方法①采用体外胚胎培养技术，将孕2?d小鼠早胚随机分组，接种到添加不同浓度抑制剂的培养液内进行培养，以观察p38MAPK特异性抑制剂对早胚发育的影响；②体内宫腔注射：取孕4?d小鼠，由子宫角注射不同浓度的SB203580，于孕8?d检查胚胎植入数，同时取子宫，观察内膜的组织学变化。结果①添加抑制剂组的早胚不能发育为胚泡，停滞在8～16细胞阶段。但去除抑制剂后继续培养，幼胚仍能发育到胚泡阶段；②注射SB203580组的小鼠，胚胎植入数明显少于对照组（P＜0.01）。镜下可见，其胚胎组织呈退化坏死状态，胚胎周围蜕膜细胞呈明显的空泡样变性,蜕膜及胚胎中均见大量血细胞浸润。结论①p38MAPK在小鼠植入前胚胎发育过程中起作用；②p38MAPK特异性抑制剂SB203580可抑制在体小鼠胚泡植入及植入后胚胎和蜕膜细胞的发育。

Effect of p38MAPK inhibitors on early development and implantation in mouse embryo

Objective To observe the biological effect of p38 MAPK inhibitors on early development and implantation in mouse embryos. Methods ① Embryo culture in vitro: early mouse embryos were randomly divided into groups and cultured with 0.2, 2, and 20μmol SB203580.② Intra-uterus injection in vivo: SB203580 of different concentrations was injected into the uterus on day 4 of pregnancy. The implantation number was calculated and the histological changes were examined on day 8 of pregnancy. Results ① In the inhibitor-treated groups, embryos did not develop to the blastocyst and were halted at the 8- to 16-cell stage. The treated embryos remained viable as the devdopmentai blockage was rescued by removing embryos from the drug treatment and placing them in a drug-free medium until they progressed to the blastocyst stage. ② The average number of embryos implanted in the p38MAPK inhibitor treated uterus was significantly lower than that in the control uterus (P<0.01). Microscopic observation demonstrated that the embryo was degenerated and even necrosed in some parts. In the decidual cells there was obvious adipose degeneration, while many blood coils were invaded in the embryos and the deciduas. Conclusion ① p38MAPK activity may be required to support embryo development through the murine pre-implantation interval. ② 008MAPK inhibitors can inhibit the blastocyst implantation and the development of embryos and decidual cells in vivo.