胎盘组织中KLF-8和MMP-9的表达及其与子痫前期发病的关系

Expression of KLF-8 and MMP-9 in placentas and their relationship with the pathogenesis of preeclampsia

目的探讨胎盘组织中Krtippel样因子8（KLF-8）和基质金属蛋白酶9（MMP-9）的表达及其与子痫前期发病的关系。方法选择2011年9月至2012年3月重庆医科大学附属第一医院以剖宫产术分娩的子痫前期孕妇22例（轻度4例、重度18例）为子痫前期组，同期孕足月行择期剖宫产术分娩的20例健康孕妇为对照组。免疫组化sP法检测胎盘组织中KLF-8蛋白的表达部位，实时荧光定量PCR技术检测胎盘组织中KLF-8mRNA的表达水平，蛋白印迹法检测胎盘组织中KLF_8及MMP-9蛋白的表达水平。结果（1）子痫前期组和对照组胎盘组织中均有KLF-8蛋白表达并主要表达于合体滋养细胞的胞核及胞质中，与对照组比较，子痫前期组胎盘组织中KLF-8蛋白阳性染色程度较弱。（2）子痫前期组胎盘组织中KLF．8mRNA表达水平为0．69±0．08，对照组为1．14±0．09。两组比较，差异有统计学意义（P〈0．01）。（3）子痫前期组KLF-8及MMP-9的蛋白表达水平分别为0．684-0．05及0．21±0．03，对照组分别为0．94±0．06、0．34±0．03，两组分别比较，差异均有统计学意义（P〈0．01）。（4）合计分析两组孕妇的胎盘组织中KLF-8蛋白与MMP-9蛋白的表达呈正相关关系（r=0．64，P〈0．01）。结论子痫前期孕妇胎盘组织中KLF-8mRNA和蛋白表达水平均明显低于健康孕妇，主要表达于与细胞侵袭密切相关的滋养细胞中，且KLF-8蛋白表达与MMP-9蛋白呈正相关。提示KLF-8可能通过影响滋养细胞侵袭力而参与子痫前期的发病。

Objective To evaluate the expression of Krtippel-like factor 8 （KLF-8） and matrix metalloproteinase 9 （MMP-9） in placentas and their relationship with the pathogenesis of preeclampsia （PE）. Methods Twenty-two women with PE （mild PE：4 cases; severe PE：18 cases） who received cesarean sections in the First Affiliated Hospital of Chongqing Medical University from September 2011 to March 2012 were recruited as the PE group （n = 22）. And twenty women who received elective term cesarean section without perinatal complications were chosen as the control group （ n = 20 ）. Placentas were collected and immunohistochemieal SP method were employed to detect the localization of KLF-8 protein. KLF-8 mRNA level was determined by quantitative real-time PCR technique and western blot analysis was used to quantify KLF-8 and MMP-9 protein levels. Results （1） There was no difference of KLF-8 protein distribution in placentas of the PE group and the control group. It was mainly located in the nuclear and cytoplasm of syncytiotrophoblasts. KLF-8 immunostaining was apparently decreased in the placentas of preeclamptic women when compared with the control group. （2）The KLF-8 mRNA levels were significantly decreased in placentas of the PE group （ 0. 69 ± 0. 08 ） compared to those of the control group （ 1.14 ± 0. 09, P 〈0. O1 ）. （3） KLF-8 and MMP-9 protein levels significantly decreased in the PE placentas （0. 68 ±0.05 and O. 21 ±0. 03） when compared to the control group （0. 94 ±0. 06 and 0. 34±O. 03, respectively, P 〈 0. O1 ）. （4） There was a positive correlation between the expression of KLF-8 and MMP-9 protein in the placentas from PE and normal pregnancies （ r = 0. 64, P 〈 0. 01 ）. Conclusions KLF-8 mRNA and protein levels were decreased in placentas of PE patients compared to those of normotensive women. KLF-8 protein was primarily located in the invasion-related trophoblast cells and its expression had a positive correlation with MMP-9 levels. KLF-8 might have an important role in the pathogenesis of PE by regulation of trophoblast invasion.