P38MAPK、Nox1及ROSmRNA在早发型重度子痫前期患者胎盘组织中的表达及意义

THE EXPRESSION LEVELS AND CLINICAL VALUES OF P38MAPK,NOX1 AND ROS MRNA IN PLACENTA OF EARLY ONSET SEVERE PREECLAMPSIA

目的探讨Nox1、P38MAPK及ROS mRNA表达与早发型重度子痫前期发病的关系,揭示早发型重度子痫前期发病基础,为临床治疗提供理论依据。方法选择早发型重度子痫前期患者32例、晚发型重度子痫前期患者30例为研究组,35例正常分娩者为对照组。胎盘娩出后立即于脐带附着处母体面,避开钙化出血梗塞区(肉眼观)剪取大小为1 cm×1 cm×1 cm的组织两块,一份用无菌生理盐水(含0.1%DEPC水)漂洗,去除血液,置于经DEPC水处理并消毒的冻存管中,于-80℃冰箱保存待行RT-PCR检测;另一份取材后即以4%多聚甲醛固定,常规脱水,浸蜡,包埋,4um切片(每例5张),载玻片经清洁处理,APES包被,进行HE染色及脂肪特染观察胎盘组织的脂肪浸润情况和形态学改变;采用RT-PCR及免疫组化方法检测胎盘组织中Nox1、P38MAPK、ROSmPNA表达水平。结果各组胎盘组织的合体滋养细胞、血管内皮细胞、蜕膜细胞中均可以检测到Nox1、P38MAPKmRNA及ROS表达。早发型重度子痫前期组Nox1mRNA表达显著高于晚发型重度子痫前期组及对照组(0.712±0.012,0.215±0.013,0.113±0.01,p<0.01);早发型重度子痫前期组ROSmRNA水平显著高于晚发型重度前期组及对照组(142.43±11.81,96.12±8.93,102.21±9.75,p<0.01);早发型重度子痫前期组P38MAPKmRNA表达水平显著高于晚发型重度前期组及对照组(0.109±0.057,0.074±0.074,0.042±0.013,p<0.01)。各组胎盘组织中Nox1表达与ROS水平呈正相关(r=0.81,p<0.05);各组胎盘组织中Nox1表达与P38MAPKmRNA呈正关(r=0.63,p<0.01)。结论早发型重度子痫前期组胎盘中Nox1mRNA高表达与其发病及发展密切相关。P38MAPK介导的P38MAPK-Nox1-ROS脂质代谢途径可能在早发型重度子痫前期发生发展中起重要作用。

Objective Study the relationship between NADPH, P38MAPK, ROS mRNA and early onset severe preeclampsia, reveal the foundation of the disease, and provide a theoretical basis of Clinical treatment. Methods The study group include thirty - two early onset severe preeclampsia ones, and thirty later onset severe preeclamp- sia ones, and the control group include thirty - five normal deliveries. Clip placental tissue （ 1 cm ~ 1 cm ~ 1 cm ） with Umbilical attachment part, remove of blood with physiological saline, dry with filter paper, and take one to fix with paraformaldehyde, the others to preserve in -80~C fridge. We detect fatty infiltration and morphological changes of placenta with the methods of HE staining and fat staining technique. We detect the different expression levels of P38MAPK, Noxl and ROS mRNA in placenta with the methods of RT - PCR and Immunohistochemistry. Results We can test the expression levels of Noxl, P38MAPK, and ROS mRNA in the syncytiotrophoblast, vascular endothelial cells and decidual ceils of the placenta. The expression level of Noxl mRNA is significantly higher in early onset severe preeclampsia ones than the levels in later onset severe preeclampsia ones and normal ones （0. 712 ± 0. 012, 0. 215 ±0. 013, 0. 113 ±0. 01, p 〈0. 01 ）. The expression level of ROS mRNA is significantly higher in early onset severe preeclampsia ones than the levels in later onset severe preeclampsia ones and normal ones （142. 43 ± 11.81, 96. 12 ± 8. 93, 102. 21 ±9. 75, p 〈0. 01 ）. The expression level of P38MAPK mRNA is significantly higher in early onset severe preeclampsia ones than the levels in later onset severe preeclampsia ones and normal ones （0. 109 ±0. 057, 0. 074 ±0. 074, 0. 042 ±0. 013, p 〈0. 01 ）. The expression levels of Noxl mRNA and ROS mRNA are positive correlation （r = 0. 81, p 〈 0. 05 ）. The Expression levels of Noxl mRNA and ≥38 MAPK mRNA are positive correlation（ r = 0. 63, p 〈 0.01 ）. Conclusion Early onset severe preeclampsia placenta Noxl mRNA expression is closely related to its onset and development. P38MAPK - Noxl - ROS lipid metabolism pathways mediated by P38MAPK play an important role in the development of early onset severe preeclampsia.