Abstract:【Objective】The purpose was to investigate whether the placental perfusion in preeclampsia model rats can be improved by transplantation of angiogenic T cells(Tang). 【Methods】Thirty adult healthy female rats were selected and kept in the same cage as the male rats at a ratio of 2:1 during the estrus period. The vaginal plug shedding was observed daily; and it was marked as pregnancy d1 when the day of the vaginal plug was seen. Then, 30 pregnant rats were randomly divided into experimental group, control group and normal group, with 10 rats in each group. The rats' model of preeclampsia was induced by intraperitoneal infected with L-NAME. The pregnant rats of the experimental group and the control group were intraperitoneally injected with L-arginine methyl ester(L-NAME) 250 mg/(kg·d) from d7 of pregnancy for 5 consecutive days, and the tail arteries of rats were measured on d7, d10, d13, d16, and d19 of pregnancy, respectively. The systolic blood pressure is found to be significantly elevated, which is regarded as the successful modeling of the preeclampsia pregnant mouse model. Umbilical venous blood was taken from healthy pregnant rats, then isolation of cord blood mononuclear cells was performed by density gradient centrifugation, followed by magnetic activated cell sorting(MACS) and flow cytometry for the isolation Tang cells. The Tang cells were transplanted by means of tail vein injection to the rats with preeclampsia. Meanwhile, the control group was injected with the same amount of normal saline in the tail vein for 6 consecutive days. No treatment was done in the normal group. The blood pressure, urine protein concentration, placental blood vessel density, placental weight, fetal weight and other indicators were compared among the three groups. The micro vascular density of placenta was detected by positive expression of CD31 as shown by inmunofluorescence histochemistry. The gestational result was observed by measurement of the weight of placenta rat fetus and placenta. 【Results】On d13, d16, and d19 of pregnancy, the blood pressure and urine protein concentration of pregnant rats in the experimental group and the control group were higher than those of the normal group; on d16, d19 of pregnancy, the blood pressure and urine protein concentration of the experimental group were significantly lower than those of the control group, and the differences were statistically significant(P<0.05). There was no significant difference in the number of fetal rats and placenta weight among the three groups(P>0.05). The birth weight and the fluorescence density of placental neovascularization of the experimental group and the control group were significantly lower than those of the normal group, but the experimental group's birth weight and the fluorescence density of placental neovascularization were significantly higher than those of the control group; and the difference was statistically significant(P<0.05). The placenta HE staining showed that the placental tissue cells of the control group were disordered, the amount of cells was small, the cell edema and vacuole-like changes were more, the placental intervascular membrane was thickened, and fibrinoid necrosis was seen. On the other hand, the placental tissue of the experimental group was more obvious than the control group Improved, there is no obvious cell edema and vacuoles, there is still a small amount of fibrinoid necrosis, and the new blood vessels are significantly increased compared with the control group.【Conclusion】Tang transplantation can increase the density of placental neovascularization in preeclampsia rats and improve pregnancy outcome, indicating that it has a certain effect on placental perfusion.
曹武占, 郭叶青, 贺鑫, 刘佳, 邓利, 陆佳黛, 姚穗. 血管生成性T淋巴细胞对子痫前期大鼠胎盘灌注的影响[J]. 医学临床研究, 2021, 38(7): 1048-1051.
CAO Wu-zhan, GUO Ye-qing, HE Xin,et al. Improvement of Placental Perfusion in Preeclampsia Model Rat by Transplantation of Angiogenic T Cells. JOURNAL OF CLINICAL RESEARCH, 2021, 38(7): 1048-1051.
[1] 谢幸, 苟文丽. 妇产科学[M].第8版. 北京:人民卫生出版社,2013:64-65. [2] VON DADELSZEN P, MAGEE L A. Pre-eclampsia:an update[J].Curr Hypertens Rep,2014, 16(8):454. [3] GOULOPOULOU S, DAVIDGE S T. Molecular mechanisms of maternal vascular dysfunction in preeclampsia[J].Trends Mol Med,2015, 21(2):88-97. [4] MOL B W,ROBERTS C T,THANGARATINAM S,et al. Preeclampsia[J].Lancet,2016,387(10022):999-1011. [5] HUR J, YANG H M, YOON C H, et al .Identification of a novel role of t cells in postnatal vasculo-genesis:characterization of endothelial progenitor cell colonies[J].Circulation,2007,116(15):1671-1682. [6] 郭叶青, 刘佳, 曹武占,等,血管生成性T淋巴细胞及内皮祖细胞与子痫前期发病的关系及两种细胞的相关性[J].中华妇产科杂志,2015, 50(10):747-751. [7] BROSSERON F,MARCUS K,MAY C.Isolating peripheral lymphocytes by density gradient centrifugation and magnetic cell sorting[J].Methods Mol Biol,2015,1295:33-42. [8] FISHER S J. Why is placentation abnormal in preeclampsia?[J].Am J Obstet Gynecol,2015, 213(4 Suppl):S115-S122. [9] ROUHL R P W, MERTENS A, VAN OOSTENBRUGGE R J, et al. Angiogenic t-cells and putative endothelial progenitor cells in hypertension-related cerebral small vessel disease[J].Stroke,2012, 43(1):256-258. [10] RODRIGUEZ-CARRIO J, ALPERI-LOPEZ M, LOPEZ P, et al. Angiogenic T cells are decreased in rheumatoid arthritis patients[J].Ann Rheum Dis,2015, 74(5):921-927. [11] CALIGIURI G, ROSSIGNOL P, JULIA P, et al. Reduced immunoregulatory CD31+ T cells in patients with atherosclerotic abdominal aortic aneurysm[J].Arterioscler Thromb Vasc Biol,2006, 26(3):618-623. [12] WEIL B R, KUSHNER E J, DIEHL K J, et al. CD31+ T cells,endothelial function and cardiovascular risk[J].Heart Lung Circ,2011, 20(10):659-662. [13] ZHU J. Transplantation of endothelial progenitor cells for improving placental perfusion in preeclamptic rats[J].Arch Gynecol Obstet,2015, 291(5):1113-1119. [14] CHRISTOFFERSSON G, VAGESJO E, VANDOOREN J , et al. Vegf-a recruits a proangiogenic mmp-9 delivering neutrophil subset that induces angiogenesis in transplanted hypoxic tissue[J].Blood,2012,120(23):4653-4662.