子痫前期母体血清PIGF、sEng浓度对脑流体动力学、脑组织损伤的影响

发布时间：2018-08-15 18:53

【摘要】：目的 ①阐明P E与正常妊娠母体血清PIGF、sEng浓度及sEng/PIGF比值的差异，评估PIGF、sEng浓度及sEng/PIGF比值在PE预测中的价值。 ②探讨PE母体脑动脉、静脉、脑脊液三大流体系统动力学、流动模式的变化及其脑静脉、脑脊液循环的调节方式。 ③探讨PE母体血清PIGF、sEng浓度对脑流体动力学的影响。材料与方法 1．研究对象选取2013年10月~2014年3月广州医科大学附属第三医院产科收治的子痫前期孕妇31例（重度PE17例，轻度PE14例）为研究对象，另招募24例健康育龄期女性及28例正常中晚期妊娠孕妇为对照研究。 2．PC-MRI测量对31例PE患者（入院当天）及24例健康育龄期女性（2013年7月~2013年9月）行BA、右侧大脑中动脉（MCA）、上矢状窦（SSS）、SS（直窦）及中脑导水管（CA）的PCMRI流动测量，其中18PE患者例于产后4~8周内行PCMRI复查。 3．血清PIGF、sEng浓度检测对该31例PE患者于入院第二天早晨空腹静脉采血5ml，28例中晚期正常妊娠孕妇于门诊空腹采静脉血5ml，离心后取血清置于-800冷藏，并采用ELISA法检测血清PIGF、sEng浓度。 4．结果观察及分析比较P E与正常妊娠母体血清PIGF、sEng浓度及sEng/PIGF值的差异，采用ROC曲线评估PIGF、sEng浓度及sEng/PIGF浓度比值用于PE诊断的价值；观察三组各测量血管及CA的时相--峰值流速曲线特征，记录舒张期及收缩期流速达峰速度和时相点，计算收缩期和舒张期流速达峰时相差，并除以16获得两峰值时相差率，比较三组曲线达峰时相差率及流体动力学间的差异；计算SSS与SS的平均流量比值，并比较三组该比值的差异。计算PE母体血清sEng/PIGF浓度比与脑流体动力学的相关性。结果 1. PE母体血清PIGF浓度低于正常妊娠，sEng及sEng/PIGF比值浓度高于正常妊娠；重度PE母体血清PIGF浓度低于轻度PE，sEng及sEng/PIGF比值浓度高于轻度PE。 2. sEng/PIGF比值预测PE的临界值为9.85，灵敏度为93.5%，特异性为100%；sEng浓度预测PE的临界值为3402.6pg/ml，灵敏度为93.5%，特异性为96.4%；PIGF浓度预测PE的临界值为359.5pg/ml，灵敏度为82.1%，特异性为90.3%。 3. PE母体BA的MF、MV、PV及血管面积均大于产后复查值；PE母体MCA的MV、PV值大于产后复查值，血管面积小于产后复查值，MF与产后复查无明显差异。 4. PE母体SSS及SS的血管面积、总MF及SS流量大于产后复查值，流速参数低于产后复查值，SS/SSS流量比值增大。 5. PE母体CA面积及收缩期、舒张期PV均高于产后复查值，净流量低于产后复查值。 6. MCA、CA时相-峰值流速曲线两波峰间时相差率小于产后复查值，BA、SSS及SS时相-峰值流速曲线两波峰间时相差率大于产后复查值。 7. PE母体产后复查脑血管及CA面积及流体动力学、流动模式与育龄期女性均无差异。 8. PE母体血清sEng/PIGF比值与BA平均流速呈正相关性，sEng/PIGF比值与CA净流量呈负相关性，sEng/PIGF值与MCA、SSS、SS平均流速无相关性。结论 1. PE母体血清sEng浓度、sEng/PIGF浓度比值显著高于正常妊娠，PIGF显著低于正常妊娠， PIGF、sEng参与了PE的病理生理过程；血清sEng/PIGF比值可作为预测PE的理想指标，截值为9.85，灵敏度为93.5%，特异性为100%。 2. PE母体颅内动脉、静脉及中脑导水管的流体动力学、流动模式均改变，产后6~8周恢复。 3. PE母体MCA血流灌注正常，BA血流过渡灌注、血管面积增大，提示后循环系统自我平衡被打破。 4.颅内静脉与脑脊液循环一起参与了颅内循环的再平衡调节，但两者调节方式不同，静脉呈“高排出”、脑脊液呈“低排出”。 5. PE母体血清sEng/PIGF比值与BA平均流量呈正相关性，而与MCA、颅内静脉平均流量无明显相关性。 6. PE母体血清sEng/PIGF比值与CA净流量呈负相关性，PIGF、sEng的比例改变可能影响了脑脊液的生成。目的： ①阐明PE母体脑血管源性水肿、细胞毒性水肿及脑出血、脑微量出血的发生率，探讨DWI在脑水肿病因鉴别中的价值。 ②探讨PE脑组织损伤与血清PIGF、sEng浓度及sEng/PIGF比值的关系，评估sEng浓度及sEng/PIGF比值在PE脑损伤预测中的价值。 ③探讨PE脑组织损伤与颅内动、静脉及脑脊液流量的关系。材料与方法： 1.研究对象选取2013年10月~2014年3月我院产科收治的子痫前期孕妇31例（重度PE17例，轻度PE14例）为研究对象，其中早发型PE13例，，晚发型PE18例。 2.MRI检查所有患者于入院当天行BA、RMCA、SSS、SS及CA的PC-MRI流动测量；同时行常规轴位T1WI、T2WI、T2/FLAIR、DWI、SWI及T2WI矢状位扫描。 3.PIGF、sEng浓度测量对该31例PE患者于入院第二天早晨空腹静脉采血5ml，离心后取血清置于-800冷藏，并采用ELISA法检测血清PIGF、sEng浓度。 4.数据记录与分析脑血管源性水肿、细胞毒性水肿及脑出血、脑微量出血的发病率并比较脑组织损伤的发病率在重、轻度PE及早发型、晚发型PE中的差异；比较血管源性脑水肿、细胞毒性脑水肿灶ADC值与正常脑实质的差异，比较颅内流体动力学、血清sEng/PIGF浓度比值在脑损伤组与无损伤组间的差异；采用ROC曲线评估血清sEng浓度、sEng/PIGF比值预测脑组织损伤的价值，并计算其临界值及相应的敏感度、特异性。结果： 31例PE患者中血管源性脑水肿8例（25.8%），细胞毒性脑水肿2例（6.5%），脑出血1例（3.2%），脑微量出血0例；17例重度PE中脑损伤10例，14例轻度PE中脑损伤1例，两者存在显著统计学差异（P0.01）；早发型PE13例中脑损伤8例，晚发型PE18例中脑损伤3例，两者存在统计学差异（P0.05）。产后4~8周复查，8例血管源性水肿病灶信号均恢复。脑水肿T1WI呈低信号，T2WI及T2/FAIR呈高信号；血管源性脑水肿DWI呈等、略高信号，ADC图呈明显高信号，细胞毒性脑水肿DWI呈明显高信号，ADC图呈明显低信号。血管源性脑水肿病灶平均ADC值显著高于相应对侧（或周边）正常脑组织平均ADC值（P0.01）；细胞毒性脑水肿病灶平均ADC值显著低于相应对侧（或周边）正常脑组织平均ADC值（P0.01）。脑损伤组BA、SS平均流量高于无脑损伤组（P0.05）， CA净流量显著低于无脑损伤组（P0.01）；脑损伤组MCA、SSS平均流量与无脑损伤组间无明显差异(P0.05)。SS平均流量与BA平均流量呈正相关（r=0.87，P=0.00），CA净流量与BA平均流量呈无相关性（r=0.11，P=0.76）。脑损伤组血清sEng、sEng/PIGF浓度比值显著高于无脑损伤组（P0.01），PIGF浓度低于无脑损伤组（P0.01）；sEng/PIGF比值预测PE脑损伤的临界值为20.0，灵敏度为81.8%，特异性为85.0%；sEng浓度预测PE的临界值为4809.4pg/ml，灵敏度为81.8%，特异性为70.0%。结论： 1. PE脑组织损伤以血管源性脑水肿最为常见，常发生于后循环供血区域，细胞毒性脑水肿及脑出血、微出血少见。 2.重度PE脑损伤发生率高于轻度PE，早发型PE脑损伤发生率高于晚发型PE。 3. DWI能准确鉴别脑水肿的病因，ADC值可反映脑组织损伤的病理生理改变。 4. PE脑组织损伤BA血流灌注显著高于无脑损伤组，SS静脉回流相应增加，且与BA流量呈正相关；CA净流出量减少，与BA流量无相关性。 5.脑损伤组血清sEng浓度、sEng/PIGF浓度比值显著高于无脑损伤组，血清PIGF、sEng可能参与了脑组织损伤的病理生理过程，sEng/PIGF比值可作为预测PE脑损伤的理想指标，其临界值为20.0，灵敏度为81.8%，特异性为85.0%。
[Abstract]:objective
(1) To clarify the difference of PIGF, sEng concentration and sEng/PIGF ratio between PE and normal pregnant women, and to evaluate the value of PIGF, sEng concentration and sEng/PIGF ratio in predicting PE.
(2) To investigate the dynamics of the cerebral arteries, veins and cerebrospinal fluid (CSF) in PE mothers and the changes of the flow patterns and the regulation of the circulation of the cerebral veins and cerebrospinal fluid (CSF).
To explore the effect of maternal serum PIGF and sEng concentration on brain fluid dynamics in PE.
Materials and methods
1. object of study
Thirty-one preeclampsia pregnant women (17 severe PE and 14 mild PE) admitted to the Obstetrics Department of the Third Affiliated Hospital of Guangzhou Medical University from October 2013 to March 2014 were selected as the study subjects. Another 24 healthy women of childbearing age and 28 normal pregnant women of middle and late pregnancy were recruited as the control group.
2.PC-MRI measurement
PCMRI flow measurements were performed in 31 PE patients (on admission day) and 24 healthy women of childbearing age (from July 2013 to September 2013), including BA, right middle cerebral artery (MCA), superior sagittal sinus (SSS), SS (straight sinus) and midbrain aqueduct (CA). PCMRI was performed in 18 PE patients within 4 to 8 weeks after delivery.
3. serum PIGF, sEng concentration detection
The fasting venous blood samples were taken from 31 PE patients in the morning of admission and from 28 normal pregnant women in the middle and late stages of pregnancy in the outpatient department. The serum samples were collected after centrifugation and placed in - 800 cold storage. The serum PIGF and sEng concentrations were detected by ELISA.
4. observation and analysis of results
The differences of PIGF, sEng concentration and sEng/PIGF value between PE and normal pregnant women were compared, and the diagnostic value of PIGF, sEng concentration and sEng/PIGF concentration ratio for PE was evaluated by ROC curve; the characteristics of peak velocity curves of blood vessels and CA were observed, the peak velocity and time point of diastolic and systolic velocity were recorded, and the recovery was calculated. The phase difference of peak flow rate between systolic and diastolic phases was obtained by dividing them by 16. The difference of phase difference rate and hydrodynamics between the three groups of curves was compared. The mean flow rate ratio of SSS to SS was calculated and the difference between the three groups was compared.
Result
1. The serum PIGF concentration of PE mothers was lower than that of normal pregnancies, the sEng and sEng/PIGF ratio concentration was higher than that of normal pregnancies, the serum PIGF concentration of severe PE mothers was lower than that of mild PE, and the sEng and sEng/PIGF ratio concentration was higher than that of mild PE.
2. The critical value of predicting PE by sEng/PIGF ratio was 9.85, the sensitivity was 93.5%, the specificity was 100%; the critical value of predicting PE by sEng concentration was 3402.6 pg/ml, the sensitivity was 93.5%, the specificity was 96.4%; the critical value of predicting PE by PIGF concentration was 359.5 pg/ml, the sensitivity was 82.1%, the specificity was 90.3%.
3. MF, MV, PV and vascular area of PE maternal BA were greater than those of postpartum reexamination; MV and PV values of PE maternal MCA were higher than those of postpartum reexamination, and vascular area was smaller than that of postpartum reexamination. There was no significant difference between MF and postpartum reexamination.
4. The blood vessel area, total MF and SS flow rate of PE maternal SSS and SS were greater than that of postpartum reexamination, flow rate parameters were lower than that of postpartum reexamination, and SS/SSS flow rate ratio increased.
5. the CA area and systolic and diastolic PV of maternal PE were all higher than those of postnatal reexamination, and the net flow rate was lower than that of postnatal review.
6. The time difference between the two peaks of MCA and CA time-peak velocity curves was smaller than that of postpartum reexamination. The time difference between the two peaks of BA, SSS and SS time-peak velocity curves was larger than that of postpartum reexamination.
7. There was no significant difference in the flow pattern of cerebrovascular and CA area and fluid dynamics between PE mothers and women of childbearing age.
8. The sEng/PIGF ratio of PE maternal serum was positively correlated with BA average flow rate, while the sEng/PIGF ratio was negatively correlated with CA net flow rate. The sEng/PIGF ratio was not correlated with MCA, SSS and SS average flow rate.
conclusion
1. The serum sEng concentration and sEng/PIGF ratio of PE mothers were significantly higher than those of normal pregnancies, and PIGF was significantly lower than that of normal pregnancies. PIGF and sEng participated in the pathophysiological process of PE. Serum sEng/PIGF ratio could be an ideal index for predicting PE, with a cut-off value of 9.85, a sensitivity of 93.5% and a specificity of 100%.
2. The hydrodynamics and flow pattern of intracranial artery, vein and midbrain aqueduct of PE maternal body were changed, and recovered at 6-8 weeks postpartum.
3. The MCA blood perfusion of PE maternal body was normal, BA blood flow was transitional perfusion, the area of blood vessel was enlarged, suggesting that the self-balance of posterior circulation system was broken.
4. Intracranial veins and cerebrospinal fluid circulation participate in the rebalancing regulation of intracranial circulation, but the two regulation modes are different, the veins are "high discharge" and the cerebrospinal fluid is "low discharge".
5. The sEng/PIGF ratio of PE maternal serum was positively correlated with BA mean flow, but not with MCA and intracranial venous flow.
6. The ratio of sEng/PIGF in PE maternal serum was negatively correlated with CA net flow. The change of the ratio of PIGF and sEng may affect the formation of CSF.
Objective:
To elucidate the incidence of cerebrovascular edema, cytotoxic edema, cerebral hemorrhage and microhemorrhage in PE mothers, and to explore the value of DWI in the etiological differentiation of cerebral edema.
(2) To investigate the relationship between brain injury of PE and serum PIGF, sEng concentration and sEng/PIGF ratio, and to evaluate the value of sEng concentration and sEng/PIGF ratio in predicting brain injury of PE.
(3) to explore the relationship between PE brain tissue damage and intracranial dynamic, venous and cerebrospinal fluid flow.
Materials and methods:
1. object of study
Thirty-one preeclampsia pregnant women (17 cases of severe PE and 14 cases of mild PE) admitted to our obstetric department from October 2013 to March 2014 were selected as the study subjects. Among them, 13 were early-onset PE and 18 were late-onset PE.
2.MRI examination
On the day of admission, all patients underwent PC-MRI flow measurements of BA, RMCA, SSS, SS and CA, and sagittal axial T1WI, T2WI, T2/FLAIR, DWI, SWI and T2WI.
3.PIGF, sEng concentration measurement
The fasting venous blood samples of 31 PE patients were collected for 5 ml in the morning of admission. The serum samples were collected after centrifugation and placed in - 800 cold storage. The serum concentrations of PIGF and sEng were detected by ELISA.
4. data recording and analysis
The incidence of cerebrovascular edema, cytotoxic edema, cerebral hemorrhage and microhemorrhage were compared and the difference of the incidence of severe, mild PE in early and late PE was compared. ROC curve was used to evaluate the value of serum sEng concentration and sEng/PIGF ratio in predicting brain tissue injury, and the critical value and corresponding sensitivity and specificity were calculated.
Result:
There were 8 cases (25.8%) of vascular brain edema, 2 cases (6.5%) of cytotoxic brain edema, 1 case (3.2%) of cerebral hemorrhage and 0 cases of micro-cerebral hemorrhage in 31 PE patients, 10 cases of severe PE middle brain injury and 1 case of mild PE middle brain injury. There were significant differences between them (P 0.01); 8 cases of early PE middle brain injury and 3 cases of late PE middle brain injury. There was statistical difference (P0.05). After 4~8 weeks of postpartum reexamination, 8 cases of angiogenic edema were recovered.
Cerebral edema showed low signal on T1WI, high signal on T2WI and T2/FAIR, vasogenic brain edema DWI, slightly high signal on ADC, cytotoxic brain edema DWI, and low signal on ADC. The average ADC value of cytotoxic brain edema lesions was significantly lower than that of the corresponding contralateral (or peripheral) normal brain tissues (P 0.01).
The average flow of BA and SS in brain injury group was higher than that in non-brain injury group (P 0.05), and the net flow of CA was significantly lower than that in non-brain injury group (P 0.01). There was no significant difference between MCA and SSS in brain injury group and non-brain injury group (P 0.05). The average flow of SS was positively correlated with the average flow of BA (r = 0.87, P = 0.00), and the net flow of CA was not correlated with the average flow of BA (r = 0.11, P = 0.76).
The ratio of sEng and sEng/PIGF in serum of brain injury group was significantly higher than that of non-brain injury group (P 0.01), and the concentration of PIGF was lower than that of non-brain injury group (P 0.01); the critical value of sEng/PIGF for predicting brain injury of PE was 20.0, the sensitivity was 81.8%, and the specificity was 85.0%; the critical value of sEng for predicting PE was 4809.4 pg/ml, the sensitivity was 81.8%, and the specificity was 70.0%.
Conclusion:
1. Vasculogenic brain edema is the most common brain tissue injury in PE. It often occurs in the blood supply area of posterior circulation. Cytotoxic brain edema and cerebral hemorrhage are rare.
2. the incidence of severe PE brain injury was higher than that of mild PE, and the incidence of early onset PE brain injury was higher than that of late onset PE..
3. DWI can accurately identify the cause of cerebral edema. ADC value can reflect the pathophysiological changes of brain tissue injury.
4. The blood flow perfusion of BA in PE brain tissue injury was significantly higher than that in non-brain injury group, and the venous reflux of SS increased correspondingly, and was positively correlated with the flow of BA; the net flow of CA decreased, but was not correlated with the flow of BA.
5. Serum sEng concentration and sEng/PIGF ratio in brain injury group were significantly higher than those in non-brain injury group. Serum PIGF and sEng may be involved in the pathophysiological process of brain injury. The ratio of sEng/PIGF can be used as an ideal index for predicting PE brain injury. The critical value of sEng/PIGF ratio was 20.0, the sensitivity was 81.8%, and the specificity was 85.0%.
【学位授予单位】：广州医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.244

【参考文献】