子痫前期患者滋养细胞中KiSS-1基因及基质金属蛋白酶9表达的临床意义

目的探讨胎盘滋养细胞中KiSS-1基因及基质金属蛋白酶(MMP)9在子痫前期发病中的作用及其与新生儿预后的相关性。方法采用RT-PCR和western blot(蛋白印迹法)检测40例子痫前期患者(其中轻度15例、重度25例,子痫前期组)和20例正常足月正常妊娠妇女(正常妊娠组)胎盘滋养细胞中KiSS-1mRNA和MMP-9mRNA及其蛋白的表达,并与其临床症状及其新生儿围产结局进行相关性分析。结果(1)子痫前期组滋养细胞中KiSS-1mRNA及其蛋白表达水平分别为1.73±0.24和(78.4±8.0)μg/100μg总蛋白,其中轻度患者为1.50±0.15和(72.4±6.9)μg/100μg总蛋白,重度患者为1.87±0.20和(83.5±3.6)μg/100μg总蛋白;均显著高于正常妊娠组的1.24±0.25和(63.4±2.7)μg/100μg总蛋白(P<0.01)。(2)子痫前期组MMP-9mRNA及其蛋白表达水平分别为0.09±0.06和(9.6±4.3)μg/100μg总蛋白,其中轻度患者为0.11±0.08和(10.0±3.2)μg/100μg总蛋白,重度患者为0.07±0.05和(7.8±2.0)μg/100μg总蛋白;均显著低于正常妊娠组的0.17±0.10和(17.9±7.3)μg/100μg总蛋白(P<0.01)。(3)子痫前期组KiSS-1mRNA及其蛋白表达水平与中心动脉压(MAP)和24h尿蛋白定量呈正相关,r分别为0.610(P=0.023)、0.713(P=0.011)和0.397(P=0.003)、0.638(P=0.002);与有、无眼底动脉痉挛呈显著正相关,r分别为0.499(P=0.000)和0.511(P=0.000)。子痫前期组MMP-9mRNA及其蛋白表达水平则与MAP、24h尿蛋白定量及有、无眼底动脉痉挛呈显著负相关,r分别为0.561(P=0.042)、0.571(P=0.022)、0.275(P=0.039)、0.375(P=0.048)、0.346(P=0.001)、0.543(P=0.000)。(4)子痫前期组MMP-9mRNA及其蛋白表达水平与新生儿体重呈显著正相关,r分别为0.651(P=0.000)和0.544(P=0.004);KiSS-1mRNA及其蛋白表达水平与其呈显著负相关,r分别为0.759(P=0.000)和0.865(P=0.000)。(5)随着新生儿窒息程度加重,MMP-9mRNA及其蛋白表达水平呈降低趋势,KiSS-1mRNA及其蛋白表达水平呈升高趋势(P均<0.05)。结论MMP-9和KiSS-1表达失衡在子痫前期发病中起重要作用,且与新生儿预后密切相关。

Clinical significance of KiSS-1 and matrix metalloproteinase-9 expression in trophoblasts of women with preeclampsia and their relation to perinatal outcome of neonates

OBJECTIVE: To investigate the role of KiSS-1 and matrix metalloproteinase (MMP) 9 in trophoblasts in the pathogenesis of preeclampsia and their relation to perinatal outcome of neonates. METHODS: RT-PCR and western blot analyses were used to detect the MMP-9 and KiSS-1 expression levels in trophoblast of 40 patients with preeclampsia (15 cases of mild and 25 cases of severe preeclampsia) (preeclampsia group) and 20 cases of term pregnancy (normal pregnancy group) and their correlations with symptoms and perinatal outcome of neonates were analyzed. RESULTS: (1) The KiSS-1mRNA and metastin expression levels in trophoblasts of preeclampsia group were 1.73 +/- 0.24 (A value) and (78.4 +/- 8.0) microg/100 microg total protein separately, those of mild preeclampsia were (1.50 +/- 0.15) and (72.4 +/- 6.9) microg/100 microg total protein, and severe preeclampsia were (1.87 +/- 0.20) and (83.52 +/- 3.57) microg/100 microg total protein, which were all significantly higher than those of normal pregnancy group 1.24 +/- 0.25, P < 0.01, and (63.4 +/- 2.7) microg/100 microg total protein, P < 0.01], especially those in severe preeclampsia. (2) The MMP-9 mRNA and MMP-9 expression levels in trophoblasts of preeclampsia group were 0.09 +/- 0.06 and (9.6 +/- 4.2) microg/100 microg total protein, those of mild preeclampsia were 0.11 +/- 0.08 and (10.0 +/- 3.2) microg/100 microg total protein, and severe preeclampsia were 0.07 +/- 0.05 and (7.8 +/- 2.0) microg/100 microg total protein, which were all significantly lower than those of normal pregnancy group 0.17 +/- 0.10, P < 0.01, and (17.9 +/- 7.3) microg/100 microg total protein, P < 0.01]. (3) The expression level of KiSS-1mRNA and metastin in preeclampsia group were positively correlated with MAP, urinary protein per 24 hours, the correlation coefficients between KiSS-1mRNA and MAP, urinary protein per 24 hours were 0.610 (P = 0.023), 0.397 (P = 0.003), and between metastin and MAP, urinary protein per 24 hours were 0.713 (P = 0.011), 0.638 (P = 0.002), separately. The expression level of KiSS-1mRNA and metastin in preeclampsia group was significantly positively correlated with the occurrence of fundus oculi artery spasm, correlation coefficients were 0.499 (P = 0.000) and 0.511 (P = 0.000). The MMP-9mRNA and MMP-9 expression levels were negatively correlated with MAP, urinary protein per 24 hours and the occurrence of fundus oculi artery spasm, correlation coefficients between MMP-9mRNA and MAP, urinary protein per 24 hours, the occurrence of fundus oculi artery spasm were 0.561 (P = 0.042), 0.275 (P = 0.039), 0.346 (P = 0.001), between MMP-9 and MAP, urinary protein per 24 hours, the occurrence of fundus oculi artery spasm were 0.571 (P = 0.022), 0.375 (P = 0.048), 0.543 (P = 0.000), separately. (4) The expression level of MMP-9 mRNA and MMP-9 of preeclampsia was positively correlated with neonatal birth weight significantly, Pearson correlation coefficient was 0.651 (P = 0.000) and 0.544 (P = 0.004) separately, while the expression levels of KiSS-1mRNA and KiSS-1 of preeclampsia were negatively correlated with neonatal birth weight significantly, Pearson correlation coefficients were 0.759 (P = 0.000) and 0.865 (P = 0.000) separately. (5) The expression level of MMP-9 showed decreased tendency with the severity of newborn asphyxia, while the expression level of KiSS-1 showed increased tendency (P < 0.05). CONCLUSION: The expression imbalance of MMP-9 and KiSS-1 in trophoblasts may play an important role in the pathogenesis of preeclampsia, and correlate to perinatal outcome of neonates.