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中华妇幼临床医学杂志(电子版)

中华妇幼临床医学杂志(电子版) ›› 2015, Vol. 11 ›› Issue (02) : 207 -213. doi: 10.3877/cma.j.issn.1673-5250.2015.02.013

所属专题： 文献；

论著

胎盘组织中牙周细菌对子痫前期孕妇妊娠结局的影响
吕莉娟1, 叶宁2,*,*(), 李心悦2, 牛建民1, 温济英1, 林小红1, 武丽3   
  1. 1. 511400　广州，广东省妇幼保健院妇产科
    2. 511400　广州，广东省妇幼保健院口腔科
    3. 511400　广州，广东省妇幼保健院保健部
  • 收稿日期:2014-10-12 修回日期:2015-03-09 出版日期:2015-04-01
  • 通信作者: 叶宁

Effects of placental periodontal pathogens on preeclampsia outcomes

Lijuan Lyu1, Ning Ye2(), Xinyue Li2, Jjianmin Niu1, Jiying Wen1, Xiaohong Lin1, Li Wu3   

  1. 1. Department of Obstetrics and Gynecology, Guangdong Women and Children Hospital, Guangzhou 511400, Guangdong Province, China
    2. Department of Stomatology, Guangdong Women and Children Hospital, Guangzhou 511400, Guangdong Province, China
    3. Health Care Department, Guangdong Women and Children Hospital, Guangzhou 511400, Guangdong Province, China
  • Received:2014-10-12 Revised:2015-03-09 Published:2015-04-01
  • Corresponding author: Ning Ye
  • About author:
    Corresponding author: Ye Ning, Email:
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引用本文：

吕莉娟, 叶宁, 李心悦, 牛建民, 温济英, 林小红, 武丽. 胎盘组织中牙周细菌对子痫前期孕妇妊娠结局的影响[J]. 中华妇幼临床医学杂志(电子版), 2015, 11(02): 207-213.

Lijuan Lyu, Ning Ye, Xinyue Li, Jjianmin Niu, Jiying Wen, Xiaohong Lin, Li Wu. Effects of placental periodontal pathogens on preeclampsia outcomes[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2015, 11(02): 207-213.

目的

探讨子痫前期(PE)合并牙周炎患者血清C反应蛋白(CRP)水平、胎盘组织中牙龈卟啉单胞菌(Pg)、伴放线放线杆菌(An)、具核梭杆菌(Fn)、直肠弯曲菌(Cr)4种牙周细菌的表达及胎盘组织中一氧化氮(NO)含量变化的意义。

方法

选择2012年1月至2013年10月于广东省妇幼保健院诊断为PE并住院分娩的25例孕妇为研究对象，并纳入PE组。此外，随机选择同期于本院建卡、定期接受产前检查并住院分娩的健康孕妇27例纳入对照组。按照是否合并牙周炎，进一步将PE组和对照组分别分为PE合并牙周炎亚组(PE-A亚组，n＝16)、PE未合并牙周炎亚组(PE-B亚组，n＝9)与正常妊娠合并牙周炎亚组(对照-A亚组，n＝10)、正常妊娠未合并牙周炎亚组(对照-B亚组，n＝17)。4组受试者的年龄构成比、体质量、孕前体质指数(BMI)等一般临床病历资料比较，差异无统计学意义(P>0.05)。本研究遵循的程序符合广东省妇幼保健院人体试验委员会制定的伦理学标准，得到该委员会批准，分组征得受试对象的知情同意，并与之签署临床研究知情同意书。分别使用免疫透射比浊法、PCR、Western blotting、Griess法对孕妇血清CRP水平、胎盘组织中牙周细菌DNA、内皮细胞型一氧化氮合成酶(eNOS)表达水平及胎盘组织中NO含量进行检测，分析组间表达水平的差异。

结果

①PE组和对照组孕妇的牙周炎患病率、PD、CAL和BOP比较，差异均无统计学意义(P>0.05)。②PE-A亚组孕妇的平均收缩压(MSBP)、平均舒张压(MDBP)、早产率和胎儿宫内受限发生率显著高于对照-A亚组和对照-B亚组，并且差异均有统计学意义(MSBP：P<0.05；MDBP：P<0.05；早产率：P<0.05；胎儿宫内受限发生率：P<0.05)。③PE-B亚组孕妇的MSBP、MDBP、早产率和胎儿宫内受限发生率亦显著高于对照-A亚组和对照-B亚组，并且差异均有统计学意义(MSBP：P<0.05；MDBP：P<0.05；早产率：P<0.05；胎儿宫内受限发生率：P<0.05)。④PE-A亚组胎儿窘迫发生率显著高于对照-B亚组，并且差异均有统计学意义(P＝0.018)。⑤PE-A亚组的分娩孕龄、胎儿出生体质量、胎盘细胞组织的NO含量、胎盘重量均显著低于对照-A亚组和对照-B亚组，并且差异均有统计学意义(分娩孕龄：P<0.05；胎儿出生体质量：P<0.05；胎盘细胞组织的NO合成量：t＝－28.8，－42.1；P<0.05；胎盘重量：P<0.05，P<0.001)。⑥PE-B亚组孕妇的平均分娩孕龄、胎儿出生体质量、胎盘重量亦显著低于对照-A亚组和对照-B亚组，并且差异均有统计学意义(分娩孕龄：P<0.05；胎儿出生体质量：P<0.05；胎盘重量：P<0.05，P<0.001 )。⑦PE-A亚组孕妇血清CRP水平、胎盘组织Pg、Aa和Cr检出率显著高于对照-B亚组，并且差异有统计学意义(血清CRP水平：P＝0.038；胎盘组织Pg、Aa和Cr检出率：χ2＝5.097，P＝0.024；χ2＝7.659，P＝0.006；P＝0.044)。⑧PE-A亚组β-actin/eNOS值显著高于PE-B亚组、对照-A亚组及对照-B亚组，并且差异均有统计学意义(P<0.05)。PE-B亚组β-actin/eNOS值显著高于对照-B亚组，并且差异均有统计学意义(P<0.05)。对照-A和对照-B亚组组间比较，差异亦有统计学意义(P<0.05)。⑨各组间胎盘指数比较，差异均无统计学意义(P>0.05)。

结论

牙周细菌及其产物可能侵入胎盘组织，通过激发机体炎症反应抑制胎盘eNOS活性，从而增加PE孕妇不良妊娠结局发生率。

关键词: 先兆子痫, 牙周炎, C反应蛋白质, 一氧化氮合酶
Objectlve

To investigate the expressions of serum C reactive protein (CRP), four common periodontal pathogens, porphyromonas gingivalis (Pg), actinobacillus actinomycetemcomitans (An), fusobacterium nucleatum (Fn), campylobacter rectus (Cr) and the alteration of NO formation in the placenta tissue of preeclampsia (PE) combined with periodontitis.

Methods

A total of 25 pregnant women who visited Guangdong Women and Children Hospital from January 2012 to October 2013 were included in this study (PE group). Meanwhile, another 27 healthy pregnant women were collected into control group. PE group and control group were both further divided into two sub-groups respectivley, PE group combined with periodontitis (PE-A sub-group, n=16), PE sub-group combined with no periodontitis (PE-B sub-group, n=9), control group combined with periodontitis (control-A sub-group, n=17), and control group combined with no periodontitis (control-B sub-group, n=10). There were no significant differences on age ratio, body weight, and body mass index (BMI) among four groups (P>0.05). The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Guangdong Women and Children Hospital. Informed consent was obtained from the parent of each participates. CRP was tested by immunological transmission turbidimetry. Four periodontal pathogens in the placenta tissues were tested by PCR. The levels of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) in placenta tissues were tested by Western blotting and Griess assay, respectively.

Results

①There were no significant differences on the incidence rate of periodontitis, PD, CAL and BOP between PE group and control group (P>0.05). ②There were significant differences on MSBP, MDBP, incidence rate of premature labor, and IUGR between PE-A sub-group and control-A sub-group, PE-A sub-group and control-B sub-group (MSBP: P<0.05; MDBP: P<0.05; incidence of premature delivery: P<0.05; IUGR: P<0.05). ③ The levels of MSBP, MDBP, incidence rate of premature labor, and IUGR between PE-B sub-group and control-A sub-group, PE-B sub-group and control-B sub-group (MSBP: t=50.5, 43.3; P<0.05; MDBP: t=13.3, 16.3; P<0.05; incidence of premature delivery: P<0.05; IUGR: P<0.05). ④ The incidence rate of fetal distress of PE-A sub-group was significant higher than that of control-B sub-group(P=0.018). ⑤ There were significant differences on gestational age, fetal birth weight, NO biosynthesis of placental tissues and placenta weight between PE-A sub-group and control-A sub-group, PE-A sub-group and control-B sub-group (gestational age: t=-7.0, -6.3; P<0.05; fetal birth weight: P<0.05; P<0.05; NO biosynthesis of placental tissues: t=-28.8, -42.1; P<0.05; placenta weight : P<0.05, P<0.001)). ⑥ There were significant differences on gestational age, fetal birth weight and placenta weight between PE-B sub-group and control-A sub-group, PE-B sub-group and control-B sub-group (gestational age: t=-5.9, -5.2, P<0.05; fetal birth weight: P<0.05; placenta weight: P<0.05, P<0.001 ). ⑦ The levels of serum CRP, incidence rates of Pg, Aa, and Cr in placental tissues of PE-A sub-groups were higher than those of control-B sub-group with significant differences (serum CRP: t=2.2, P=0.038; incidence rates of Pg, Aa, and Cr in placental tissues: χ2=5.097, P=0.024; χ2=7.659, P=0.006; P=0.044). ⑧ The b-actin/ eNOS value of PE-A sub-group was higher than that of PE-B sub-group, control-A sub-group and control-B sub-group, with significant differences (P<0.05). ⑨There were no significant differences on placental index among four groups (P>0.05).

Conclusions

Periodontal pathogens /byproducts may invade the placenta tissues and stimulate the inflammatory response against the activity of eNOS in placenta tissues. Then periodontal pathogens may lead to the exacerbation of PE adverse pregnancy outcomes.

Key words: Pre-eclampsia, Periodontitis, C-reactive protein, Nitric oxide synthase
表1 牙周细菌引物序列长度
Table 1 Sequences length of primer of periodental pathogens
牙周细菌 引物序列 扩增片段长度(bp)
Pg 正向引物5'-TGTAGATGACTGATGGTGAAAACC-3' 131
反向引物5'-ACGTCATCCACACCTTCCTC-3' ?
Aa 正向引物5'-GCTAATACCGCCTAGAGTCGT-3' 235
反向引物5'-ATTTCACACCTCACTTAAAGGT-3' ?
Fn 正向引物5'-GGCCACAAGGGGACTGAGACA-3' 185
? 反向引物5'-TTTAGCCGTCACTTCTTCTGTTGG-3' ?
Cr 正向引物5'-TTTCGGAGCGTAAACTCCTTT TC-3' 598
? 反向引物5'-TTTCTGCAAGCAGACACTCTT-3' ?
表2 PE组和对照组孕妇牙周检查结果比较(±s)
Table 2 Comparison of periodontal examination between PE group and control group (±s)
组别 例数 牙周炎患病率例数(%) PD(mm) CAL(mm) BOP例数(%)
PE组 25 16(64) 3.51±1.02 3.41±0.93 18(72.00)
对照组 27 10(37) 3.44±0.95 3.32±0.86 14(51.85)
t值/χ2值 ? 3.775 0.980 0.158 2.23
P值 ? 0.095 0.327 0.693 0.136
表3 4组孕妇妊娠结局比较(±s)
Table 3 Comparison of pregnancy results among four groups (±s)
组别 例数 年龄(岁) MSBP(mmHg)a MDBP (mmHg)b 孕前BMI(kg/m2) 分娩孕龄(孕周)c
PE组 ? ? ? ? ? ?
? PE-A亚组 16 28.0±4.4 156.2±21.7 95.6±16.8 23.4±3.3 32.9.±2.7
? PE-B亚组 9 29.0±3.6 159.1±23.1 92.1± 9.2 23.1±2.6 33.9±2.5
对照组 ? ? ? ? ? ?
? 对照-A亚组 10 25.0±3.6 108.1±13.1 78.1±9.2 21.3±4.2 39.9±0.8
? 对照-B亚组 17 26.0±7.2 116.1±12.4 75.7±7.8 21.6±4.4 39.1±0.9
t/χ2值 ? 2.102 28.5 19.1 1.9 38.0
P值 ? 0.112 0.000 0.000 0.139 0.000
组别 出生体质量(g)d 胎儿宫内窘迫[例数(%)]e 早产[例数(%)]f FGR[例数(%)]g 生后1 min Apgar评分(分) 生后5 min Apgar评分(分)
PE组 ? ? ? ? ? ?
? PE-A亚组 2130±371 5(31) 13(81) 11(69) 8.6±0.7 9.8±0.4
? PE-B亚组 2044±384 3 (8) 8(89) 5(56) 8.6±0.7 9.9±0.3
对照组 ? ? ? ? ? ?
? 对照-A亚组 3184±308 1(10) 0 (0) 0 (0) 8.9±0.3 9.9±0.3
? 对照-B亚组 3284±358 0 (0) 0 (0) 0 (0) 9.0±0.0 10.0±0.0
t值/χ2值 44.7 10.1 48.4 32.0 7.7 1.1
P值 0.000 0.018 0.000 0.000 0.053 0.355
表4 牙周菌在胎盘组织的分布及胎盘组织的NO含量情况
Table 4 The distribution of periodontal bacteria and the metabolism of NO in placenta
组别 例数 血清CRPa 胎盘组织中检出牙周细菌b 胎盘氧代谢β-actin/eNOSc NO(μmol/L)d 胎盘系数 胎盘重量(g)e
Pg Aa Fn Cr
PE组 ? ? ? ? ? ? ? ? ? ?
? PE-A亚组 16 7.7±3.1 11(68.75) 9(56.00) 7(43.75) 4(25.00) 16.1±2.6 35.5±16.7 0.2±0.1 467.9±104.4
? PE-B亚组 9 7.1±2.2 3(33.33) 3(33.33) 2(22.22) 1(11.11) 12.7±3.5 49.7±15.0 0.2±0.0 441.0± 97.3
对照组 ? ? ? ? ? ? ? ? ? ?
? 对照-A亚组 10 5.8±2.3 4(40.00) 3(30.00) 2(20.00) 0(0.00) 10.8±2.6 64.3±23.6 0.2±0.0 593.4±119.9
? 对照-B亚组 17 5.9±1.9 4(23.50) 1 (5.88) 2(11.76) 0(0.00) 7.7±2.1 77.6±16.8 0.2±0.0 603.5± 83.7
t值/χ2值 ? 2.0 10.1 10.98 4.695 8.647 28.3 17.2 2.7 8.8
P值 ? 0.126 0.018 0.012 0.196 0.034 0.000 0.000 0.057 0.000
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