TGFβ_1,Bcl-2与妊娠期高血压疾病胎盘细胞凋亡的关系

Bcl-2, TGFβ_1, and apoptosis in placenta tissues in patients with hypertensive disorder complicating pregnancy

目的:研究妊娠期高血压疾病患者胎盘组织的细胞凋亡以及TGFβ1和Bcl-2与细胞凋亡的关系,进一步探讨妊娠期高血压疾病发病机制。方法:收集妊娠期高血压疾病患者胎盘组织45例(15例妊娠期高血压,15例子痫前期轻度,15例子痫前期重度)和正常孕妇对照组45例。应用免疫组织化学染色法(SP法)检测胎盘绒毛滋养层TGFβ1和Bcl-2蛋白的表达;应用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL法)检测胎盘绒毛组织中滋养层细胞凋亡情况,并测定凋亡率。结果:妊娠期高血压疾病组较对照组胎盘绒毛组织中滋养层细胞凋亡率及TGFβ1表达明显增高,而Bcl-2表达明显减低(均P<0.01)。随病情加重,妊娠期高血压组、子痫前期轻度组、子痫前期重度组细胞凋亡率及TGFβ1表达呈上升趋势,Bcl-2表达呈下降趋势(均P<0.01)。子痫前期重度组、子痫前期轻度组胎盘绒毛细胞凋亡发生率与TGFβ1呈正相关;与Bcl-2表达呈负相关(均P<0.05)。子痫前期重度组、子痫前期轻度组TGFβ1与Bcl-2表达呈负相关(均P<0.05)。结论:妊娠期高血压疾病胎盘细胞凋亡率明显增高,TGFβ1在滋养层细胞表达增高,Bcl-2在滋养层细胞表达降低,TGFβ1和Bcl-2平衡失调可能导致妊娠期高血压疾病的发生。

Objective To determine the apoptosis in placenta tissues of patients with hypertensive disorder complicating pregnancy and its relationship with Bcl-2, TGFβ1 , and to explore the etiology of hypertensive disorder complicationg pregnancy. Methods Forty-five placenta samples were obtained from pregnancies with hypertensive disorder （15 gestational hypertension, 15 mild preeclampsia, and 15 severe preeclampsia） and 45 normal placenta tissues were enrolled from the third- trimester pregnancies. Immunohistochemistry （ SP method） was used to study the expression of Bcl-2 and TGFβ1 in human trophoblasts. Terminal deoxynucleotidyl transferase-dUTP nick end-labeling （TUNEL） was used to quantify the incidence of appoptosis in human trophoblasts. Results The apoptosis rate and TGFβ1 expression in hypertensive disorder complicating pregnancy group was higher than that in the control group, but the Bcl-2 expression was significantly lower than the control group （ all P 〈 0.01 ） . With the aggravation of this illness, the apoptosis rate and TGFβ1 expression in the gestational hypertension group, mild preeclampsia group, and severe preeclampsia tended to be increasing, but the Bcl-2 expression was decreasing （ P 〈 0. 001 ）. The apoptosis of placenta villi and TGFβ1 expression were positively correlated in the severe preeclampsia group and mild preeclamp- sia group, but the apoptosis of placenta villi and Bcl-2 were negatively correlated （all P1 〈 0.05 ）. TGFβ1 and Bcl-2expressions in the severe preeclampsia group and mild preeclampsia group were nega- tively correlated （ P 〈 0.05 ）. Conclusion Apoptosis of the placental trophoblasts of pregnancies with hypertensive disorder is evidently enhanced. The TGFβ1 expression increases and the Bcl-2 ex- pression decreases. The imbalance between TGFβ1 and Bcl-2 expression may induce the hypertensive disorder.