胎盘组织KiSS-1及metastin表达在早发重度子痫前期发病中的作用及其与围生结局的相关研究

The role of placental expression of KiSS-1 and its peptin metastin in pathogenesis of early-onset severe preeclampsia and their relation to perinatal outcome

目的:探讨胎盘组织中KiSS-1及其蛋白肽metastin表达在早发重度子痫前期发病中的作用及其与围生结局的相关性。方法:采用RT-PCR、westernblot、免疫组化方法检测57例子痫前期患者(轻度15例和重度42例,其中早发重度12例,晚发重度30例)和30例正常晚期妊娠者胎盘组织中KiSS-1及其蛋白的表达水平和定位,并与围生结局进行相关性分析。结果:子痫前期胎盘组织中KiSS-1及蛋白肽metastin的表达定位与正常晚期胎盘组织相似,主要表达在绒毛的合体滋养细胞和细胞滋养细胞。子痫前期组胎盘组织中KiSS-1mRNA及其蛋白表达分别为(1.73±0.24)和(78.41±7.96)μg/100μg总蛋白,显著高于正常晚期妊娠组(P<0.01、P<0.01),以重度子痫前期组尤为显著,早发重度子痫前期组显著高于晚发重度子痫前期组。与正常晚期妊娠组相比,子痫前期组metastin平均光密度(0.64±0.02)显著增高(P<0.01),随着病情的加重而逐渐增高,早发重度子痫前期组显著高于晚发重度子痫前期组(P<0.01)。随着新生儿窒息程度的加重,KiSS-1mRNA及其蛋白表达水平呈升高趋势(P<0.05、P<0.05),且与窒息程度呈明显正相关,r分别为0.463(P=0.016)和0.587(P=0.027)。KiSS-1mRNA及其蛋白表达水平与新生儿体重呈显著负相关,r分别为-0.764(P=0.000)和-0.899(P=0.000)。结论:子痫前期存在KiSS-1基因及其表达增强,且早发重度子痫前期组表达显著高于晚发重度子痫前期组,与滋养细胞侵润能力下降和新生儿预后密切相关,其异常表达可能是早发重度子痫前期发病的主要原因之一且与围生结局密切相关。

Objective： To investigate the role of KiSS - 1 and its peptin metastin in placenta in the pathogenesis of early - onset severe preeclampsia and their relation to perinatal outcome of neonates. Methods： RT - PCR analysis, Western blot analysis and immunohistochemistry were used to detect the KiSS - 1 expression levels and cellular distribution in placenta of 57 cases of patients with preeclampsia （ 15 cases of mild and 42 cases of severe preeclampsia, which including 12 cases of early - onset severe preeclamsia and 30 cases of late - onset） and 30 cases of term. Their correlations with perinatal outcome of neonates were analyzed. Results： The expression of KiSS - 1 peptin metastin distributed ih placenta of preeclampsia were similar to those in term, which were mostly found in syncytiotrophoblast and cytotrophoblast. The KiSS - 1 mRNA and metastin expression in preeclampsia were （ 1.73 ±0.24） and （78. 41 ±7. 96） μg/100 μg total protein separately, which was significantly higher than those of term （ P 〈 0.01, P 〈 0.01 ） , especially those in severe preeclampsia, in which those in early - onset severe preeclampsia were higher than those in late - onset. Compared with term, the mean density of metastin in preeclampsia placenta （0. 64 ± 0. 02） was significantly higher accompany with the development of preeclampsia, and those in sever early - onset preeclampsia were higher than those in late - onset preeclampsia （ P 〈 0. 01 ） . The expression level of KiSS - 1 and metastin showed an increased tendency with the severity of newborn asphyxia （ P 〈 0.05, P 〈 0.05 ）, which showed a positive correlation significantly, Pearson correlation coefficients were 0. 463 （P = 0. 016） and 0. 587 （P = 0. 027） separately. The expression levels of KiSS -1 mRNA and metastin were negatively correlated with neonatal birth weight sigificantly, Pearson correlation coefficients were 0. 764 （P = 0. 000） and 0. 899 （P = 0. 000） separately. Conduslon： There is an increasing expression of KiSS- 1 in preeclampsia, which is higher significantly in early onset severe preeclampsia than those in late - onset, and is correlated with low invasive ability of trophoblast and pefinatal outcome of neonates significantly. Abnormal expression of KiSS - 1 may be one of the reasons of pathogenesis of early - onset severe preeclampsia and correlated with the perinatal outcome.