中华妇产科杂志
中華婦產科雜誌
중화부산과잡지
CHINESE JOUNAL OF OBSTETRICS AND GYNECOLOGY
2015年
7期
493-499
,共7页
仙娜%陈维萍%张妍%李静%张宁%叶元华
仙娜%陳維萍%張妍%李靜%張寧%葉元華
선나%진유평%장연%리정%장저%협원화
先兆子痫%糖基化终产物,高级%受体,免疫%肿瘤坏死因子α
先兆子癇%糖基化終產物,高級%受體,免疫%腫瘤壞死因子α
선조자간%당기화종산물,고급%수체,면역%종류배사인자α
Pre-eclampsia%Glycosylation end products,advanced%Receptors,immunologic%Tumor necrosis factor-alpha
目的探讨孕妇血清及胎盘组织中晚期糖基化终末产物（AGE）及晚期糖基化终末产物受体（RAGE）的表达水平变化与子痫前期发病的相关性。方法选择2013年12月至2014年6月在青岛大学附属医院产科住院的重度子痫前期孕妇32例为重度子痫前期组，选取同期晚期妊娠健康孕妇30例为健康对照组，两组孕妇均为剖宫产术分娩。采用ELISA法检测孕妇血清中AGE、可溶性晚期糖基化终末产物受体（sRAGE）、肿瘤坏死因子α（TNF-α）及胎盘组织中AGE、TNF-α的水平；免疫组化SP法检测胎盘组织中AGE、RAGE蛋白的表达定位；实时荧光定量PCR技术检测胎盘组织中RAGE和TNF-αmRNA的表达水平；蛋白印迹法（western blot）检测胎盘组织中AGE、RAGE及TNF-α蛋白的表达水平。结果（1）重度子痫前期组孕妇血清中AGE、sRAGE及TNF-α水平分别为（538±75）、（367±86）及（322±40）ng/L，均显著高于健康对照组的（454±50）、（286±35）及（270±35）ng/L，两组分别比较，差异均有统计学意义（P<0.05）。重度子痫前期组孕妇血清AGE水平与TNF-α水平呈显著正相关（r=0.588，P<0.05），sRAGE水平与TNF-α水平无相关性（r=-0.041，P>0.05）。（2）重度子痫前期组胎盘组织中AGE及TNF-α水平分别为（500±82）及（334±57）ng/L，明显高于健康对照组的（431±74）及（263±46）ng/L，两组分别比较，差异均有统计学意义（P<0.05）。重度子痫前期组孕妇胎盘组织中AGE水平与TNF-α水平呈显著正相关（r=0.406，P<0.05）。（3）重度子痫前期组及健康对照组胎盘组织中AGE及RAGE蛋白均主要定位表达于胎盘合体滋养细胞、巨噬细胞及血管内皮细胞，AGE主要定位于细胞质内，RAGE主要定位于细胞膜和细胞质内。（4）重度子痫前期组胎盘组织中RAGE及TNF-αmRNA的表达水平分别为12.6±4.6及10.4±2.4，均高于健康对照组的0.9±0.4及3.5±0.9，两组分别比较，差异均有统计学意义（P<0.01）。（5）重度子痫前期组胎盘组织中AGE、RAGE及TNF-α蛋白的表达水平分别为0.68±0.06、0.82±0.08及0.76±0.08，均显著高于健康对照组的0.46±0.05、0.42±0.09及0.52±0.07，分别比较，差异均有统计学意义（P<0.01）。结论重度子痫前期孕妇血清及胎盘组织中AGE及RAGE表达水平明显高于健康孕妇，同时伴有胎盘组织炎性因子TNF-α水平的明显升高，提示AGE及RAGE可能通过诱发孕妇全身和胎盘局部炎性反应参与子痫前期的发病过程。
目的探討孕婦血清及胎盤組織中晚期糖基化終末產物（AGE）及晚期糖基化終末產物受體（RAGE）的錶達水平變化與子癇前期髮病的相關性。方法選擇2013年12月至2014年6月在青島大學附屬醫院產科住院的重度子癇前期孕婦32例為重度子癇前期組，選取同期晚期妊娠健康孕婦30例為健康對照組，兩組孕婦均為剖宮產術分娩。採用ELISA法檢測孕婦血清中AGE、可溶性晚期糖基化終末產物受體（sRAGE）、腫瘤壞死因子α（TNF-α）及胎盤組織中AGE、TNF-α的水平；免疫組化SP法檢測胎盤組織中AGE、RAGE蛋白的錶達定位；實時熒光定量PCR技術檢測胎盤組織中RAGE和TNF-αmRNA的錶達水平；蛋白印跡法（western blot）檢測胎盤組織中AGE、RAGE及TNF-α蛋白的錶達水平。結果（1）重度子癇前期組孕婦血清中AGE、sRAGE及TNF-α水平分彆為（538±75）、（367±86）及（322±40）ng/L，均顯著高于健康對照組的（454±50）、（286±35）及（270±35）ng/L，兩組分彆比較，差異均有統計學意義（P<0.05）。重度子癇前期組孕婦血清AGE水平與TNF-α水平呈顯著正相關（r=0.588，P<0.05），sRAGE水平與TNF-α水平無相關性（r=-0.041，P>0.05）。（2）重度子癇前期組胎盤組織中AGE及TNF-α水平分彆為（500±82）及（334±57）ng/L，明顯高于健康對照組的（431±74）及（263±46）ng/L，兩組分彆比較，差異均有統計學意義（P<0.05）。重度子癇前期組孕婦胎盤組織中AGE水平與TNF-α水平呈顯著正相關（r=0.406，P<0.05）。（3）重度子癇前期組及健康對照組胎盤組織中AGE及RAGE蛋白均主要定位錶達于胎盤閤體滋養細胞、巨噬細胞及血管內皮細胞，AGE主要定位于細胞質內，RAGE主要定位于細胞膜和細胞質內。（4）重度子癇前期組胎盤組織中RAGE及TNF-αmRNA的錶達水平分彆為12.6±4.6及10.4±2.4，均高于健康對照組的0.9±0.4及3.5±0.9，兩組分彆比較，差異均有統計學意義（P<0.01）。（5）重度子癇前期組胎盤組織中AGE、RAGE及TNF-α蛋白的錶達水平分彆為0.68±0.06、0.82±0.08及0.76±0.08，均顯著高于健康對照組的0.46±0.05、0.42±0.09及0.52±0.07，分彆比較，差異均有統計學意義（P<0.01）。結論重度子癇前期孕婦血清及胎盤組織中AGE及RAGE錶達水平明顯高于健康孕婦，同時伴有胎盤組織炎性因子TNF-α水平的明顯升高，提示AGE及RAGE可能通過誘髮孕婦全身和胎盤跼部炎性反應參與子癇前期的髮病過程。
목적탐토잉부혈청급태반조직중만기당기화종말산물（AGE）급만기당기화종말산물수체（RAGE）적표체수평변화여자간전기발병적상관성。방법선택2013년12월지2014년6월재청도대학부속의원산과주원적중도자간전기잉부32례위중도자간전기조，선취동기만기임신건강잉부30례위건강대조조，량조잉부균위부궁산술분면。채용ELISA법검측잉부혈청중AGE、가용성만기당기화종말산물수체（sRAGE）、종류배사인자α（TNF-α）급태반조직중AGE、TNF-α적수평；면역조화SP법검측태반조직중AGE、RAGE단백적표체정위；실시형광정량PCR기술검측태반조직중RAGE화TNF-αmRNA적표체수평；단백인적법（western blot）검측태반조직중AGE、RAGE급TNF-α단백적표체수평。결과（1）중도자간전기조잉부혈청중AGE、sRAGE급TNF-α수평분별위（538±75）、（367±86）급（322±40）ng/L，균현저고우건강대조조적（454±50）、（286±35）급（270±35）ng/L，량조분별비교，차이균유통계학의의（P<0.05）。중도자간전기조잉부혈청AGE수평여TNF-α수평정현저정상관（r=0.588，P<0.05），sRAGE수평여TNF-α수평무상관성（r=-0.041，P>0.05）。（2）중도자간전기조태반조직중AGE급TNF-α수평분별위（500±82）급（334±57）ng/L，명현고우건강대조조적（431±74）급（263±46）ng/L，량조분별비교，차이균유통계학의의（P<0.05）。중도자간전기조잉부태반조직중AGE수평여TNF-α수평정현저정상관（r=0.406，P<0.05）。（3）중도자간전기조급건강대조조태반조직중AGE급RAGE단백균주요정위표체우태반합체자양세포、거서세포급혈관내피세포，AGE주요정위우세포질내，RAGE주요정위우세포막화세포질내。（4）중도자간전기조태반조직중RAGE급TNF-αmRNA적표체수평분별위12.6±4.6급10.4±2.4，균고우건강대조조적0.9±0.4급3.5±0.9，량조분별비교，차이균유통계학의의（P<0.01）。（5）중도자간전기조태반조직중AGE、RAGE급TNF-α단백적표체수평분별위0.68±0.06、0.82±0.08급0.76±0.08，균현저고우건강대조조적0.46±0.05、0.42±0.09급0.52±0.07，분별비교，차이균유통계학의의（P<0.01）。결론중도자간전기잉부혈청급태반조직중AGE급RAGE표체수평명현고우건강잉부，동시반유태반조직염성인자TNF-α수평적명현승고，제시AGE급RAGE가능통과유발잉부전신화태반국부염성반응삼여자간전기적발병과정。
Objective To investigate the correlation of the expressions of advanced glycation end products(AGE) and the receptor for advanced glycation end products(RAGE) in serum and placenta with the pathogenesis of preeclampsia. Methods From December 2013 to June 2014, 32 women with severe preeclampsia who received cesarean section in the Affiliated Hospital of Qingdao University were recruited in the study, defined as the severe preeclampsia group. 30 healthy pregnant women who received cesarean section in the same hospital were recruited as the control group. ELISA was used to measure the maternal serum AGE, soluble receptor for advanced glycation end products (sRAGE) and tumor necrosis factor-α(TNF-α) in these women. Furthermore, ELISA was also used to measure AGE and TNF-α in the placenta. The localizations of AGE and RAGE protein in placentas were detected by immunohistochemical SP method. RAGE and TNF-α mRNA expression in placentas were measured by real-time quantitative PCR. AGE, RAGE and TNF-αprotein expression in placentas were measured by western blot, respectively. Results (1) The serum levels of AGE,sRAGE and TNF-αin the severe preeclampsia group were (538 ± 75),(367 ± 86) and (322 ± 40) ng/L,respectively. They were significantly higher than those in the control group[(454 ± 50), (286 ± 35) and (270 ± 35) ng/L, respectively](P<0.05). The levels of AGE showed positive correlation with the levels of TNF-α(r=0.588,P<0.05),while the levels of sRAGE showed no correlation with TNF-α(r=-0.041, P>0.05). (2) In the severe preeclampsia group, the levels of AGE and TNF-αin placentas were (500 ± 82) and (334 ± 57) ng/L, which were higher than those in the control group [(431 ± 74) and (263 ± 46) ng/L, respectively](P<0.05). The levels of AGE showed positive correlation with the levels of TNF-ɑ(r=0.406,P<0.05). (3)AGE and RAGE protein mainly located in the syncytiotrophoblasts, macrophages and vascular endothelial cells in the placentas of the two groups. AGE expressed mainly in the cytoplasm, and RAGE expressed in the cytoplasm and cell membranes.(4)RAGE and TNF-αmRNA expression in the placentas of the severe preeclampsia group were 12.6 ± 4.6 and 10.4 ± 2.4, which were significantly higher than those in the control group (0.9 ± 0.4 and 3.5 ± 0.9,P<0.01). (5) The expressions of AGE、RAGE and TNF-αprotein in placentas of the severe preeclampsia group were 0.68 ± 0.06, 0.82 ± 0.08 and 0.76 ± 0.08. All were significantly higher than those of the control group (0.46 ± 0.05,0.42 ± 0.09 and 0.52 ± 0.07;P<0.01). Conclusions The levels of AGE and RAGE in serum and placentas elevated in the severe preeclampsia group, and the expression of TNF-αalso elevated. These indicated that AGE and RAGE might be involved in the systemic inflammatory response and local inflammatory response in placentas, and then caused the preeclampsia.
