NO在小鼠早期胚胎吸收过程中的作用

Research on the Role of NO in Early Embryo Resorption in Mice

给妊娠 7d小鼠尾静脉注射细菌脂多糖 (L PS)诱导早期胚胎吸收。注射 L PS后 12、2 4、36 h,以 EL ISA、比色法检测血清和子宫匀浆中 Th1型细胞因子 IFN- γ、IL- 12与 NO的含量变化 ;免疫组织化学法观察 3种一氧化氮合酶(n NOS,e NOS,i NOS)和 Th2型细胞在小鼠子宫表达的变化。此外 ,还观察了 NO供体硝普钠 (SNP)诱导孕鼠流产效果及氨基胍 (AG)对抗 L PS诱导孕鼠流产的效果。结果显示 ,相对于正常妊娠组 ,L PS处理组孕鼠子宫匀浆 NO含量及 IFN- γ、IL- 12水平极显著升高 (P<0 .0 1) ,血清 NO含量也极显著升高 (P<0 .0 1) ;n NOS、i NOS在 L PS处理组小鼠子宫可见阳性标记 ,而 e NOS未见阳性标记 ;大量 Th2型阳性细胞标记仅在正常妊娠组小鼠子宫内膜基质可见 ,L PS处理组未见阳性细胞。腹腔注射 SNP致使孕鼠早期胚胎吸收 ,然而妊娠 6～ 9d腹腔注射 AG却未能降低 L PS诱导的孕鼠早期胚胎吸收。上述结果提示 ,L PS处理后 ,Th1型免疫反应增强 ;源自升高表达的 i NOS的子宫局部高浓度 NO可能作为一种效应分子介导小鼠早期胚胎吸收。

Intravenous injection of Lipopolysaccharide(LPS) induced fetus resorption on day 7 of gestation in mice.Variation of producton of NO and cytokines including IFN γ,IL 12 was measured both in serum and in homogenized uterus at 12,24,36 hours after administrated with LPS.Using immunohistochemistry,the changing expression of three NOS isolforms,nNOS,eNOS,iNOS, and Th2 cells in uterus were also detected at same time.Compared with normal pregnancy,there were significantly higher produciton ( P <0 01) of NO,IFN γ and IL 12 measured in homogenized uterus of mice administrated with LPS.The serum levels of NO were also higher ( P <0 01) than normal.The nNOS and iNOS were all expressed in uterus of mice treated with LPS,while the staining of eNOS was negative.Numerous positive cells of Th2 were only found in uterus of normal pregnancy.Intraperitoneal injection of sodium nitroprusside(SNP),a donor of NO,led to the early embryo resorption.However,Aminoguanidine,a selective inhibitor of eNOS and nNOS,did not to reduce the early embryo resorption of mice induced by LPS when given parenterally on day 6 to day 9 of gestation.The results presented strongly suggested that a role of NO derived from iNOS may act as an effector molecule in induction of the early embryo resorption in mice.