Abstract:Objective To discuss the expression of ADMA and DDAH2 in plasma and placental and the correlation between the two factors in early onset severe preeclampsia (EPSP). To approach the possible role of DDAH2 and ADMA in the pathogenesis and progression of EPSP. And to seek the basis of early diagnosis and treatment of disease based on pathogenesis. Methods From January 2017 to January 2018, 45 cases with severe preeclampsia in Guangdong Maternal and Child Health Hospital ("our hospital" for short) were selected as the experimental group, of which 25 cases in early onset severe preeclampsia group, 20 cases in late onset severe preeclampsia group, and 35 healthy pregnant women delivery in our hospital during the same period were selected as the control group. The expression levels of ADMA and DDAH2 in sera and placenta tissues of two groups were detected with Enzyme-linked immunosorbent assay (ELISA). Spearman linear correlation analysis was used for correlation analysis. Results The expression level of ADMA in serum of early-onset severe preeclampsia was significantly higher than that of later onset severe preeclampsia and control group (P < 0.05). The expression level of ADMA of later onset severe preeclampsia in serum was significantly higher than that of control group (P < 0.05). The expression level of DDAH2 of in serum of early onset severe preeclampsia group was significantly lower than that of later onset severe preeclampsia group and control group (P < 0.05). The expression level of DDAH2 in serum of later onset severe preeclampsia group was significantly lower than that of control group (P < 0.05). The positive staining rate of ADMA in the placenta tissues of early onset severe preeclampsia was significantly higher than that of late onset severe preeclampsia (P < 0.05). The positive staining rate of ADMA in the placenta tissue of late onset severe preeclampsia was significantly higher than that of control group (P < 0.05). The positive staining rate of DDAH2 in the placenta tissues of early onset severe preeclampsia was significantly lower than that of late onset severe preeclampsia (P < 0.05). The positive staining rate of DDAH2 in the placenta tissues of late onset severe preeclampsia was significantly lower than that of control group (P < 0.05). The expression levels of DDAH2 and ADMA in serum and in the placenta tissues of earlyonset severe preeclampsia appeared in a obvious negative correlation (r = -0.77, P < 0.05). Conclusion The significantly higher expression level of ADMA and the significantly lower expression level of DDAH2 in serum and in the placenta tissue of early onset severe preeclampsia, they are negatively correlated. ADMA and DDAH2 are closely related to early onset severe preeclampsia. They may interact with each other in the process of trophoblast infiltration and participate pathogenesis of the early onset severe preeclampsia.
赵莉娜 李嘉蔚 刘国成. 早发型重度子痫前期中ADMA与DDAH2的表达水平及临床意义[J]. 中国医药导报, 2018, 15(36): 71-74,82.
ZHAO Li′na Li Jiawei LIU Guocheng. Expression level and clinical significance of ADMA and DDAH2 in earlyonset severe preeclampsia. 中国医药导报, 2018, 15(36): 71-74,82.
[1] 米杰.心血管病的发育起源及早期干预窗口期[J].中华预防医学杂志,2016(1):1-3.
[2] Raymond D,Peterson E. A critical review of early-onset and late-onset preeclampsia [J]. Obstet Gynecol Surv,2011, 66(8):497-506.
[3] 张丹,张炯,王金泉.非对称性二甲基精氨酸在慢性肾病中的研究进展[J].医学研究生学报,2018,31(01):83-87.
[4] 谢幸、苟文丽.妇产科学[M].8版.北京:人民卫生出版社,2013:64-67.
[5] Fromowitz FB,Viola MV,Chao S,et al. Ras p21 expression in the progression of breast cancer [J]. Hum Pathol,1987,18(12):1268
[6] von Leitner EC,Klinke A,Atzler D,et al. Pathogenic cycle between the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine and the leukocyte-derived hemoprotein myeloperoxidase [J]. Circulation,2011,124(24):2735-2745.
[7] Zhang J,Liu J,Li Z,et al. Dysfunction of endothelial NO system originated from homocysteine-induced aberrant methylation pattern in promoter region of DDAH2 gene [J]. Chin Med J,2007,120(23):2132-2137.
[8] Anderssohn M,Maa?覻 LM,Diemert A,et al. Severely decreased activity of placental dimethylarginine dimethylaminohydrolase in pre-eclampsia [J]. Eur J Obstet Gynecol Reprod Biol,2012,161(2):152-156.
[9] Das UN,Repossi G,Dain A,et al. L-arginine,NO and asymmetrical dimethylarginine in hypertension and type 2 diabetes [J]. Front Biosci,2011,16(1):13-20.
[10] Seppa N. Preeclampsia progress:Blood test for predicting pregnancy problems [J]. Science News,2003,163(19):293-293.
[11] Bahtiyar MO,Buhimschi C,Ravishankar V,et al. Contrasting effects of chronic hypoxia and nitric oxide synthase inhibition on circulating angiogenic factors in a rat model of growth restriction [J]. Am J Obstet Gynecol,2007,196(1):72.el-e6.
[12] Zheng JJ,Wang HO,Huang M,et al. Assessment of ADMA,estradiol,and progesterone in severe preeclampsia [J]. Clinical and Experimental Hypertension,2016,38(4):347-351.
[13] Gumus E,Atalay MA,Cetinkaya Demir B,et al. Possible role of asymmetric dimethylarginine (ADMA) in prediction of perinatal outcome in preeclampsia and fetal growth retardation related to preeclampsia [J]. J Matern Fetal Neonatal Med,2016,29(23):3806-3811.
[14] Ghebremariam YT,Erlanson DA,Yamada K,et al. Development of a dimethylarginine dimethylaminohydrolase (DDAH) assay for high-throughput chemical screening [J]. J Biomol Screen,2012,17(5):651-661.
[15] Alacam H,Dikmen ZG,Yaman H,et al. The role of asymmetric dimethyl arginine and oxidant/antioxidant system in preeclampsia [J]. Fetal Pediatr Pathol,2011,30(6):387-393.
[16] 向兰花,周小峰,钟敏.子痫前期患者血清中sEng,ADMA含量与胎盘缺氧损伤,细胞凋亡的相关性[J].海南医学院学报,2017,23(5):627-630.
[17] Pope AJ,Karuppiah K,Cardounel AJ. Role of the PRMT-DDAH-ADMA axis in the Regulation of Endothelial Nitric Oxide Production [J]. Pharmacol Res,2009,60(6):461-465.
[18] 冯梅.体外转染二甲基精氨酸二甲胺水解酶改善高胆固醇血症兔胸主动脉内皮功能不全[D].长沙:中南大学,2005.
[19] Tsukahara H,Ohta N,Tokuriki S,et al. Determination of asymmetric dimethylarginine,an endogenous nitric oxide synthase inhibitor,in umbilical blood [J]. Metabolism,2008,57(2):215-220.