中华妇产科杂志
中華婦產科雜誌
중화부산과잡지
CHINESE JOUNAL OF OBSTETRICS AND GYNECOLOGY
2011年
1期
36-40
,共5页
罗欣%刘丹丹%漆洪波%姚珍薇
囉訢%劉丹丹%漆洪波%姚珍薇
라흔%류단단%칠홍파%요진미
先兆子痫%p38丝裂原活化蛋白激酶类%内皮,血管%血管内皮生长因子受体1%受体,细胞表面%抗原,CD
先兆子癇%p38絲裂原活化蛋白激酶類%內皮,血管%血管內皮生長因子受體1%受體,細胞錶麵%抗原,CD
선조자간%p38사렬원활화단백격매류%내피,혈관%혈관내피생장인자수체1%수체,세포표면%항원,CD
Pre-eclampsia%p38 Mitogen-activated protein kinases%Endothelium,vascular%Vascular endothelial growth factor receptor-1%Receptors,cell surface%Antigens,CD
目的 探讨p38丝裂原活化蛋白激酶(MAPK)信号分子在子痫前期患者血管内皮细胞损伤中的作用.方法选择2009年9月至2010年3月在重庆医科大学附属第一医院住院分娩的足月产妇54例为研究对象,其中36例为子痫前期患者,按病情分为子痫前期轻度组(20例)、子痫前期重度组(16例);同期足月择期剖宫产孕妇为对照组(18例).采用CD34标记血管内皮细胞,计数各组胎盘微血管密度(MVD);SP法检测磷酸化的p38 MAPK(p-p38 MAPK)在胎盘组织中的定位;蛋白印迹法检测各组胎盘p38 MAPK及p-p38 MAPK的蛋白表达差异;双抗体夹心ELISA法检测各组血清中可溶性血管内皮生长因子受体1(sFlt-1)及可溶性内皮糖蛋白(soluble endoglin,sEng)的水平.结果 (1)MVD:对照组、子痫前期轻度组及子痫前期重度组患者胎盘MVD分别为103±3、81±5、63±4,各组间两两比较,差异均有统计学意义(P＜0.05).(2)p38 MAPK和p-p38 MAPK蛋白表达水平:对照组、子痫前期轻度组及子痫前期重度组患者胎盘组织p38 MAPK蛋白表达水平分别为0.84±0.05、0.90±0.14、0.86±0.18,各组间两两比较,差异均无统计学意义(P＞0.05);p-p38 MAPK蛋白的表达水平分别为0.13±0.05、0.59±0.12和1.16±0.18,各组间两两比较差异均有统计学意义(P＜0.05).(3)p-p38 MAPK蛋白的表达部位:p-p38 MAPK蛋白主要表达于胎盘滋养层细胞的胞质及胞核、血管内皮细胞及少量间质细胞的胞核.(4)sFlt-1及sEng的水平:①对照组孕妇血清sFlt-1、sEng水平分别为(5.2±0.3)、(10.9-±0.4)μg/L;子痫前期轻度组分别为(12.5±1.2)、(20.4±5.3)μg/L;子痫前期重度组分别为(19.3±3.0)、(29.5±3.7)μg/L;各组sFlt-1、sEng水平两两比较,差异均有统计学意义(P＜0.05);②p-p38 MAPK蛋白表达水平与血清sFlt-1、sEng水平的相关性:子痫前期重度组和子痫前期轻度组p-p38 MAPK蛋白表达水平与血清sFlt-1、sEng水平均呈明显正相关(r=0.68,P＜0.05;r=0.87,P＜0.05).结论 子痫前期患者胎盘组织中p38 MAPK信号分子的显著活化,使血清中sFlt-l、sEng水平升高,损伤胎盘血管内皮细胞,导致胎盘MVD降低;p38 MAPK信号分子可能是子痫前期患者血管内皮细胞损伤的关键信号传导通路之一.
目的 探討p38絲裂原活化蛋白激酶(MAPK)信號分子在子癇前期患者血管內皮細胞損傷中的作用.方法選擇2009年9月至2010年3月在重慶醫科大學附屬第一醫院住院分娩的足月產婦54例為研究對象,其中36例為子癇前期患者,按病情分為子癇前期輕度組(20例)、子癇前期重度組(16例);同期足月擇期剖宮產孕婦為對照組(18例).採用CD34標記血管內皮細胞,計數各組胎盤微血管密度(MVD);SP法檢測燐痠化的p38 MAPK(p-p38 MAPK)在胎盤組織中的定位;蛋白印跡法檢測各組胎盤p38 MAPK及p-p38 MAPK的蛋白錶達差異;雙抗體夾心ELISA法檢測各組血清中可溶性血管內皮生長因子受體1(sFlt-1)及可溶性內皮糖蛋白(soluble endoglin,sEng)的水平.結果 (1)MVD:對照組、子癇前期輕度組及子癇前期重度組患者胎盤MVD分彆為103±3、81±5、63±4,各組間兩兩比較,差異均有統計學意義(P＜0.05).(2)p38 MAPK和p-p38 MAPK蛋白錶達水平:對照組、子癇前期輕度組及子癇前期重度組患者胎盤組織p38 MAPK蛋白錶達水平分彆為0.84±0.05、0.90±0.14、0.86±0.18,各組間兩兩比較,差異均無統計學意義(P＞0.05);p-p38 MAPK蛋白的錶達水平分彆為0.13±0.05、0.59±0.12和1.16±0.18,各組間兩兩比較差異均有統計學意義(P＜0.05).(3)p-p38 MAPK蛋白的錶達部位:p-p38 MAPK蛋白主要錶達于胎盤滋養層細胞的胞質及胞覈、血管內皮細胞及少量間質細胞的胞覈.(4)sFlt-1及sEng的水平:①對照組孕婦血清sFlt-1、sEng水平分彆為(5.2±0.3)、(10.9-±0.4)μg/L;子癇前期輕度組分彆為(12.5±1.2)、(20.4±5.3)μg/L;子癇前期重度組分彆為(19.3±3.0)、(29.5±3.7)μg/L;各組sFlt-1、sEng水平兩兩比較,差異均有統計學意義(P＜0.05);②p-p38 MAPK蛋白錶達水平與血清sFlt-1、sEng水平的相關性:子癇前期重度組和子癇前期輕度組p-p38 MAPK蛋白錶達水平與血清sFlt-1、sEng水平均呈明顯正相關(r=0.68,P＜0.05;r=0.87,P＜0.05).結論 子癇前期患者胎盤組織中p38 MAPK信號分子的顯著活化,使血清中sFlt-l、sEng水平升高,損傷胎盤血管內皮細胞,導緻胎盤MVD降低;p38 MAPK信號分子可能是子癇前期患者血管內皮細胞損傷的關鍵信號傳導通路之一.
목적 탐토p38사렬원활화단백격매(MAPK)신호분자재자간전기환자혈관내피세포손상중적작용.방법선택2009년9월지2010년3월재중경의과대학부속제일의원주원분면적족월산부54례위연구대상,기중36례위자간전기환자,안병정분위자간전기경도조(20례)、자간전기중도조(16례);동기족월택기부궁산잉부위대조조(18례).채용CD34표기혈관내피세포,계수각조태반미혈관밀도(MVD);SP법검측린산화적p38 MAPK(p-p38 MAPK)재태반조직중적정위;단백인적법검측각조태반p38 MAPK급p-p38 MAPK적단백표체차이;쌍항체협심ELISA법검측각조혈청중가용성혈관내피생장인자수체1(sFlt-1)급가용성내피당단백(soluble endoglin,sEng)적수평.결과 (1)MVD:대조조、자간전기경도조급자간전기중도조환자태반MVD분별위103±3、81±5、63±4,각조간량량비교,차이균유통계학의의(P＜0.05).(2)p38 MAPK화p-p38 MAPK단백표체수평:대조조、자간전기경도조급자간전기중도조환자태반조직p38 MAPK단백표체수평분별위0.84±0.05、0.90±0.14、0.86±0.18,각조간량량비교,차이균무통계학의의(P＞0.05);p-p38 MAPK단백적표체수평분별위0.13±0.05、0.59±0.12화1.16±0.18,각조간량량비교차이균유통계학의의(P＜0.05).(3)p-p38 MAPK단백적표체부위:p-p38 MAPK단백주요표체우태반자양층세포적포질급포핵、혈관내피세포급소량간질세포적포핵.(4)sFlt-1급sEng적수평:①대조조잉부혈청sFlt-1、sEng수평분별위(5.2±0.3)、(10.9-±0.4)μg/L;자간전기경도조분별위(12.5±1.2)、(20.4±5.3)μg/L;자간전기중도조분별위(19.3±3.0)、(29.5±3.7)μg/L;각조sFlt-1、sEng수평량량비교,차이균유통계학의의(P＜0.05);②p-p38 MAPK단백표체수평여혈청sFlt-1、sEng수평적상관성:자간전기중도조화자간전기경도조p-p38 MAPK단백표체수평여혈청sFlt-1、sEng수평균정명현정상관(r=0.68,P＜0.05;r=0.87,P＜0.05).결론 자간전기환자태반조직중p38 MAPK신호분자적현저활화,사혈청중sFlt-l、sEng수평승고,손상태반혈관내피세포,도치태반MVD강저;p38 MAPK신호분자가능시자간전기환자혈관내피세포손상적관건신호전도통로지일.
Objective To study expression and activation of p38 mitogen activated protein kinase (MAPK) in vascular endothelial cells dysfunction in preeclampsia. Methods From Sept. 2009 to Mar.2010, 54 pregnant women underwent deliveries in the First Affiliated Hospital of Chongqing Medical University were enrolled in this study, including 20 patients in mild preeclampsia group, 16 patients in severe preeclampsia group and 18 women with term cesarean section without perinatal complications as control group. Placental endothelial cells were labeled by CD34 to assay microvessel density (MVD) of each group. Immunohistochemical SP and western blot were used to detect localization and expression of p-p38 MAPK protein, respectively. The levels of sera soluble fms-like tyrosine kinase-1 (sFlt-1)and soluble endoglin(sEng) were measured by ELISA. Results ①The MVD of placenta were 103 ± 3 in control group, 81 ±5 in mild preeclampsia group and 63±4 in severe group, respectively, which showed statistical difference among each group (P＜0.05).②The expression of p38 MAPK protein were 0.84±0.05 in control group,0.90±0.14 in mild group and 0. 86 ±0.18 in severe group, which did not reach remarkable difference among each group (P＞0.05). The expression of p-p38 MAPK protein were 0.13±0.05 in control group,0.59±0.12 in mild group and 1.16±0.18 in severe group, which show statistical difference among each group(P＜0.05).(3) The localization of p-p38 was in trophoblast, endothelial cells and a few (5.2±0.3)and(10.9±0.4)μg/L in control group,(12.5±1.2) and (20.4±5.3)μg/L in mild group and (19.3±3.0) and (29. 5 ±3.7) μg/L in severe group. When drawing paired comparison in those p-p38 MAPK protein levels and the concentrations of serum sFlt-1, sEng in preeclampsia groups (r=0.68,P＜0.05;r=0.87,P＜0.05). Conclusions The remarkable activation of the p38 MAPK in the placenta of patients with preeclampsia induced the increased levels of sFlt-1 and sEng in maternal serum, which confer the injury of vascular endothelial cells that caused the significant decline of MVD in placentas. p38 MAPK signaling might be one of the key pathways in vascular endothelial cell dysfunction in preeclampsia.
