子痫前期患者血清中sFlt-1和sEng水平及胎盘中Endoglin表达的研究
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摘要
目的:通过对子痫前期患者血清中的可溶性血管内皮生长因子受体1 (soluble fms-like tyrosine kinase-1,sFlt-1)和可溶性Endoglin(soluble Endoglin,sEng)的表达水平以及胎盘中Endoglin蛋白的表达水平的测定,探讨它们在子痫前期发病的作用、以及与子痫前期病情严重程度的关系。方法:选取2008年10月至2009年10月在泸州医学院附属医院住院分娩的子痫前期患者40例,按照乐杰主编的全国统编教材《妇产科学》第7版的诊断和分类标准进行分类,其中包括10例轻度子痫前期组,30例重度子痫前期组。选取同期健康孕妇40例作为对照组。采用酶联免疫吸附试验(ELISA)夹心法检测子痫前期患者与正常妊娠妇女血清中的sFlt-1和sEng的表达水平,了解两组间sFlt-1和sEng的表达是否存在差异。并通过免疫组化SP法测定子痫前期患者与正常妊娠妇女胎盘中Endoglin蛋白的表达水平来了解两组间Endoglin蛋白的表达水平是否存在差异,以及它与血清中sEng的关系。采用SPSS 14.0统计软件包进行统计学分析,数据以均数±标准差(x±s)表示;两样本均数比较用随机独立样本均数t检验;两变量间的相关关系用Pearson直线相关分析。取a=0.01作为检验水平,P<0.01差异有统计学意义。结果:1.子痫前期组血清sFlt-1为939.27±109.48ng/L,正常妊娠组为279.24±147.39ng/L,两组比较差异有显著性(p<0.01)。重度痫前期组血清中sFlt-1为941.76±159.01ng/L,轻度痫前期组血清中sFlt-1为928.13±141.27ng/L,两组比较差异无统计学意义(p>0.05)。2.子痫前期组血清中sEng为7.38±1.78ng/ml正常妊娠组为2.17±0.59ng/ml,两组比较差异有显著性(p<0.01)。重度痫前期组血清中sEng为7.94±1.27ng/ml,轻度痫前期组血清中sEng为5.72±1.09ng/ml,重度子痫前期与轻度子痫前期比较,差异有显著性(p<0.01)。血清中sEng的水平随疾病病情的加重而升高。3.子痫前期组胎盘组织中Endoglin的平均光密度为0.462±0.057,正常妊娠组为0.219±0.042,两组比较差异有显著性(p<0.01);轻度子痫前期组胎盘组织中Endoglin的平均光密度为0.382±0.035,重度子痫前期组胎盘组织中Endoglin的平均光密度为0.488±0.054,两组比较差异有显著性(p<0.01)。子痫前期胎盘组织中Endoglin的平均光密度随疾病病情的加重而升高。4.相关性分析:胎盘组织中Endoglin的平均光密度与血清中sEng的水平呈正相关关系(r>0.9,p<0.01)。血清中sEng的水平随胎盘组织中Endoglin的平均光密度的增强而升高。结论:sEng在子痫前期患者的外周血中高表达,sEng升高的水平与子痫前期临床症状的严重程度呈正相关,其升高程度能反映疾病的严重程度。sFlt-1在子痫前期患者的外周血中高表达,但与子痫前期的严重程度没有直接关系。因此我们认为升高的sFlt-1和sEng共同参与了子痫前期的病理生理过程,但它们分别有不同的作用。Endoglin蛋白在子痫前期胎盘中的表达增高,它随着疾病病情的加重而逐渐升高。而且胎盘中Endoglin蛋白表达水平与血清中sEng浓度呈明显的正相关关系,提示sEng可能主要是由胎盘分泌进入母体循环的。
Objective:By observing the level of serum soluble fins-like tyrosine kinase-1(sFlt-1),soluble Endoglin (sEng) and the expression of Endoglin in placenta in patients with preeclampsia to investigate their roles in patients with preeclampsia and the correlation these parameters with severity degree of preeclampsia. Methods:40 patients in Department of Obstetrics of the Affiliated Hospital of Lu Zhou Medical College were collected from October 2008 to October 2009.Among the 40 patients,10 cases were mild preeclampsia and 30 cases were sever preeclampsia according to the diagnostic and classification criteria based on "Obstetrics and Gynecology"(edited by Lejie, the seventh edition).40 healthy pregnant women were selected as the control group over the same period. The serum level of sFlt-1 and sEng were measured by using enzyme-linked immune-sorbent assay (ELISA) in 40 patients with preeclampsia and 40 control group.So we can learn whether there is difference in the serum level of sFlt-1 and sEng between the two groups. Immunohistochemistry SP method was used to detect the expressions of Endoglin protein in preeclampsia placentas and in normal placentas.So we can learn whether there is difference in the expression of Endoglin between the two groups and learn the relationship between the expression of Endoglin in the placenta and sEng in the serum. Datum were represented by mean±standard deviation(x±s).The result were analyzed using Independent-Samples T Test and Pearson Correlation Test by SPSS 14.0 statistic software. There was a statistical significance when the P value less than the 0.01 level. Result:1.The level of sFlt-1 in the serum was 939.27±109.48ng/L in preeclampsia group and 279.24±147.39ng/L in normal group.Serum sFlt-1 levels in patients with preeclampsia significantly higher than those in controls(p<0.01).The level of sFlt-1 in maternal serum was 941.76±159.01ng/L in sever preeclampsia group and 928.13±141.27ng/L in mild preeclampsia group.There were no statistical significant difference in serum sFlt-1 among patients with preeclampsia(p>0.05).2. The level of sEng in the serum was 7.38±1.78ng/ml in preeclampsia group and 2.17±0.59ng/ml in normal group.Serum sEng levels in patients with preeclampsia significantly higher than those in controls(p<0.01).The level of sEng in maternal serum was 7.94±1.27ng/ml in sever preeclampsia group and 5.72±1.09 ng/ml in mild preeclampsia group.The sEng levels were higher in severe preeclampsia compared to mild. There was a significant difference in serum sEng among patients with preeclampsia(p<0.01).Serum sEng levels increased in accordance with the severity of preeclampsia.3.The mean optical density of Endoglin protein expressed in placenta was 0.462±0.057 in preeclampsia group and 0.219±0.042 in normal group. The mean optical density of Endoglin protein expressed in placenta in preeclampsia group was significantly higher than those in control group (p<0.01);The mean optical density of Endoglin protein expressed in placenta was 0.382±0.035 in mild preeclampsia group and 0.488±0.054 in sever preeclampsia group.The mean optical density of Endoglin protein expressed in placenta was significant higher in severe preeclampsia compared to mild.(p<0.01).The mean optical density of Endoglin protein expressed in placenta increased in accordance with the severity of preeclampsia.4.Correlation analyses showed the levels of the mean optical density of Endoglin protein expressed in placenta had a positive correlation with serum sEng levels(r>0.9,p<0.01).Serum sEng levels increased in accordance with the increase of the mean optical density of Endoglin protein expressed in placenta. Conclusion:Serum sEng level was significantly increased in patients with preeclampsia and increased with the severity degree of diseases.Serum sFlt-1 level was significantly increased in patients with preeclampsia. However it is not directly related to the severity of preeclampsia. We conclude that elevated sFlt-1 and sEng are involved in the pathogenesis of preeclampsia with cooperative, but different roles.The expression of Endoglin protein in placenta was significantly increased in patients with preeclampsia and increased with the severity degree of diseases.The expression of Endoglin protein in placenta had a positive correlation with serum sEng levels, indicating that sEng in the maternal circulation probably was secreted mainly by the placenta.
引文
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