Neuroprotective effects of neural stem cells pretreated with neuregulin1ß on PC12 cells exposed to oxygen-glucose deprivation/reoxygenation.

Studies on ischemia/reperfusion (I/R) injury suggest that exogenous neural stem cells (NSCs) are ideal candidates for stem cell therapy reperfusion injury. However, NSCs are difficult to obtain owing to ethical limitations. In addition, the survival, differentiation, and proliferation rates of transplanted exogenous NSCs are low, which limit their clinical application. Our previous study showed that neuregulin1ß (NRG1ß) alleviated cerebral I/R injury in rats. In this study, we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1ß on PC12 cells injured by oxygen-glucose deprivation/reoxygenation (OGD/R). Our results found that 5 and 10 nM NRG1ß promoted the generation and proliferation of NSCs. Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1ß improved the level of reactive oxygen species, malondialdehyde, glutathione, superoxide dismutase, nicotinamide adenine dinucleotide phosphate, and nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial damage in injured PC12 cells; these indexes are related to ferroptosis. Research has reported that p53 and solute carrier family 7 member 11 (SLC7A11) play vital roles in ferroptosis caused by cerebral I/R injury. Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4 (GPX4) was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells, but this change was alleviated after co-culturing NSCs with damaged PC12 cells. These findings suggest that NSCs pretreated with NRG1ß exhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.

[Correlation of lipocalin-2 and its receptor expressions with preeclampsia].

OBJECTIVE: To research the correlation of the expressions of lipocalin-2 (LCN-2) and its receptor (NGALR) in serum and placenta with preeclampsia. METHODS: From Dec.2010 to Apr.2011, 64 women with preeclampsia who delivered in Affiliated Hospital of Qingdao University Medical College were recruited in the study, including 26 women with moderate preeclampsia (MPE group) and 38 women with severe preeclampsia (SPE group). Twenty-five healthy pregnant women were taken as control group. LCN-2 and NGALR mRNA and protein expression in placenta were measured by reverse transcription-PCR (RT-PCR) and western blot, respectively. RESULTS: (1) The serum levels of LCN-2 in MPE group and SPE group [(58 ± 20), (90 ± 18) µg/L] were significantly higher than that in control group [(19 ± 6) µg/L, P < 0.01]; the serum LCN-2 level in SPE group was significantly higher than that in MPE group (P < 0.01). (2) LCN-2 mRNA expression in placenta in MPE group and SPE group (0.55 ± 0.14, 0.61 ± 0.14) were both significantly higher than that in control group (0.28 ± 0.16, P < 0.01); LCN-2 protein expression in placenta of MPE group and SPE group (2.2 ± 0.4, 2.4 ± 0.5) were also significantly higher than that in control group (1.4 ± 0.4, P < 0.01), no significant difference was found between MPE group and SPE group (P > 0.05). (3) No significant difference was found in the expressions of NGALR mRNA in placenta among MPE group, SPE group and control group (0.46 ± 0.11, 0.46 ± 0.14, 0.45 ± 0.15, P > 0.05). (4) NGALR protein expressions in MPE group, SPE group and control group were 2.7 ± 0.8, 3.0 ± 0.9, and 2.7 ± 0.9, and there were no significant difference among these three groups (P > 0.05). (5) In preeclampsia, serum LCN-2 level significant associated with 24 hours total urinary protein and uric acid (r = 0.565, 0.476, P < 0.01). LCN-2 serum level were not associated with systolic pressure and diastolic pressure (P > 0.05); there were no association with the expressions LCN-2 mRNA and protein in placenta (P > 0.05). CONCLUSIONS: Serum LCN-2 level is closely related to the progress of preeclampsia. Increasing expression of LCN-2 in placenta may be a compensatory response to preeclampsia.

[Association between plasma levels of soluble leukocyte differentiation antigens CD40/CD40 ligand and kidney damage in preeclamptic patients].

OBJECTIVE: To investigate the variance levels of plasma soluble leukocyte differentiation antigens CD40 (sCD40) and soluble CD40 ligand (sCD40 L) in preeclamptic patients with renal damage and its relationship. METHODS: A total of 63 pregnant women attended the Department of Obstetrics, Affiliated Hospital of Qingdao University Medical College between August 2008 and June 2010. In the present study included 28 pregnant women with mild preeclampsia and 35 patients with severe preeclampsia. Thirty matched normotensive pregnant women were enrolled in the study as the control group. Expression of sCD40 and sCD40 L were determined by ELISA. At the same time, the blood routine, C reaction protein (CRP), urine routine, 24 hours urine protein excretion, and serum uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN) were measured. The correlation analysis was performed between the sCD40/sCD40 L and the blood biochemical indexes in 3 groups. RESULTS: (1) The median levels of CRP in severe preeclampsia (10.8 mg/L) and mild preeclampsia group (7.1 mg/L) are significantly higher than that of control group (3.3 mg/L, P < 0.05); The level of CRP in severe preeclampsia group was also higher than that of mild preeclampsia group (P < 0.05). The median gestational age at delivery in severe preeclampsia (32.5 weeks) was significantly less than that of mild preeclampsia group (37.2 weeks) and normal group (38.6 weeks, P < 0.05). However no significant differences were observed between mild preeclampsia group and normal group (P > 0.05). The platelet count in severe preeclampsia (132 × 109/L) was significantly less than those of mild preeclampsia group (212 × 109/L) and normal group (216 × 109L, P < 0.01), but no significant differences were observed in blood platelet amount between mild preeclampsia group and normal group (P > 0.05). There was no significant difference in hemoglobin level and white blood cell in three groups (P > 0.05). (2) The sCD40 plasma concentration in severe, mild preeclampsia and normal group was 133.6, 126.5 and 90.7 ng/L, respectively. The sCD40 L plasma concentrations were 12.5, 10.4 and 4.4 ng/L respectively in the 3 groups. 24 hours urinary protein quantitative was 4.5 g/d, 0.8 g/d and 0 in the 3 groups respectively. And the UA level was 486 µmol/L, 289 µmol/L and 162 µmol/L. In the above three groups, the monitoring indicators were significantly higher in women with severe preeclampsia group compared with mild preeclampsia and control groups (P < 0.01), and there were also higher in mild preeclampsia group than that in control groups (P < 0.01). The level of plasma Cr (89 µmol/L) and BUN (5.32 mmol/L) in severe preeclampsia group were higher than those of mild preeclampsia group (66 µmol/L and 4.49 mmol/L) and control group (57 µmol/L and 3.32 mmol/L, P < 0.05). There was no significant difference between mild preeclampsia group and normal group (P > 0.05). (3) The correlation analysis indicated that the level of sCD40 has a positive correlation with 24 hours urinary protein quantitative (r = 0.434, P < 0.05), also significant positive correlation (r = 0.536, 0.528, P < 0.01) between the level of sCD40 and UA or CRP in women with preeclampsia. There was no significant correlation between the level of sCD40 and systolic blood pressure, diastolic blood pressure, delivery gestational age, Cr, BUN, and platelet count (r = 0.135, 0.183, -0.133, 0.190, 0.167, -0.221, all P > 0.05). There were positive correlation between the level of sCD40 L and 24 hours urine protein excretion, either UA or CRP (r = 0.591, 0.445, 0.539, all P < 0.01). No significant correlation was found between sCD40 L and systolic blood pressure, diastolic blood pressure, delivery gestational age, Cr, BUN, and platelet count (r = 0.178, 0.212, -0.292, 0.144, 0.135, -0.273, all P > 0.05). There was significant positive correlation between plasma sCD40 and sCD40 L (r = 0.707, P < 0.01). There was no relationship between the level of sCD40, sCD40 L and the blood biochemical indexes in normotensive pregnant women (P > 0.05). CONCLUSIONS: The plasma concentrations of sCD40 and sCD40 L are significantly higher in pregnant women with preeclampsia compared with the control, which may be involved in the development of preeclampsia and contribute to the kidney damage. The variance levels of sCD40 and sCD40 L may be also related to the severity of preeclampsia.

[Correlation of angiopoietin-2 and angiopoietin-2 receptor expressions in serum and placenta with preeclampsia].

OBJECTIVE: To investigate the correlation of the expressions of angiopoietin-2 (Ang-2) and angiopoietin-2 receptor (Tie-2) in serum and placenta with preeclampsia. METHODS: From May 2009 to April 2010, 62 women with preeclampsia who delivered in Affiliated Hospital of Qingdao University Medical College were recruited in the study, including 30 women with moderate preeclampsia (MPE group) and 32 women with severe preeclampsia (SPE group). Another 30 healthy pregnant women were taken as control group. ELISA was used to measure the serum Ang-2 in these women. Semiquantitative reverse transcription (RT)-PCR was used to investigate the expressions of Ang-2 mRNA and Tie-2 mRNA in placenta. Western blot was used to determine the expression of Ang-2 protein in placenta. RESULTS: (1) The serum concentrations of Ang-2 in MPE group and SPE group were (5.4 ± 1.8) µg/L and (5.1 ± 1.7) µg/L, respectively. Both were significantly lower than that in control group (16.2 ± 4.5) µg/L (P < 0.01). There was no significant difference between MPE group and SPE group (P > 0.05). (2) The expressions of Ang-2 mRNA in placenta of MPE group (2.1 ± 0.7) and SPE group (2.0 ± 0.6) were both significantly lower than that of control group (5.8 ± 0.8; P < 0.01). But there was no significant difference in Ang-2 mRNA expression between MPE group and SPE group (P > 0.05). (3) No significant difference was found in the expressions of Tie-2 mRNA in placenta among MPE group (1.33 ± 0.04), SPE group (1.35 ± 0.05) and control group (1.34 ± 0.04; P > 0.05). (4) The expressions of Ang-2 protein in placenta of MPE group (2.0 ± 0.8) and SPE group (2.0 ± 0.8) were both significantly lower than that of control group (5.7 ± 0.9; P < 0.01), while no significant difference was found between MPE group and SPE group (P > 0.05). (5) In MPE group and SPE group, the serum concentrations of Ang-2 were positively correlated with the levels of Ang-2 mRNA and Ang-2 protein in placenta (r = 0.651, 0.627; P < 0.01). CONCLUSIONS: Decreased expressions of Ang-2 mRNA and Ang-2 protein in placenta reduced serum concentration of Ang-2. Low expression of Ang-2 may be involved in the pathophysiological process of preeclampsia by affecting the formation of placenta in early pregnancy.

[Expression of macrophage migration inhibitory factor and CD74 in preeclamptic placenta and its correlation with preeclampsia].

OBJECTIVE: To investigate the expression of macrophage migration inhibitory factor (MIF) and CD74, the receptor of MIF, in preeclamptic placenta and its correlation with the pathogenesis of preeclampsia. METHODS: From March 2008 to November 2008, 69 preeclamptic women who delivered in the Department of Obstetrics, Affiliated Hospital of Qingdao University Medical College, were recruited, including 33 women with mild preeclampsia (MPE group) and 36 women with severe preeclampsia (SPE group). Another 43 healthy pregnant women were taken as control group. Immunoturbidimetry was applied to measure the concentrations of C-reactive protein (CRP) in maternal blood. The expressions of MIF and CD74 in placenta were tested with immunohistochemistry and the expressions of MIF mRNA and CD74 mRNA were detected by semiquantitative RT-PCR. The relationship between maternal blood level of CRP and MIF mRNA and CD74 mRNA in placenta was analyzed in the MPE and SPE group. RESULTS: (1) MIF and CD74 were expressed in the placenta of all pregnant women in the 3 groups, as shown in brown-yellow color, and significantly higher expression was found in the MPE and SPE group. (2) The expression of MIF mRNA and CD74 mRNA in the MPE group (0.70+/-0.13 and 0.96+/-0.16), SPE group (0.88+/-0.12 and 1.08+/-0.15) were significantly higher than in the control group (0.67+/-0.11 and 0.83+/-0.14) (P<0.01), and statistical significance was also found between the MPE and SPE group (P<0.01). (3) The maternal blood concentrations of CRP in the MPE and SPE group were significantly higher than in the control group [(15.3+/-7.0) mg/L and (21.6+/-9.1) mg/L vs (4.8+/-1.8) mg/L, P<0.01], and significant difference was also found between the MPE and SPE group (P<0.01). (4) In the two preeclamptic groups, the blood concentrations of CRP were positively correlated with the expression of both MIF mRNA (r=0.67, P<0.01) and CD74 mRNA (r=0.83, P<0.01) in placenta. Positive correlation was also found between the levels of MIF mRNA and CD74 mRNA in placenta (r=0.93, P<0.01). CONCLUSIONS: Overexpression of MIF and CD74 in the placenta may up-regulate the CRP level in maternal blood, resulting in systemic inflammatory reaction and vascular endothelium damage which may be involved in the pathogenesis of preeclampsia.

[Correlation of oxidized low-density lipoprotein and lectin-like oxidized low-density lipoprotein receptor-1 with pre-eclampsia].

OBJECTIVE: To investigate the role of oxidized low-density lipoprotein (oxLDL) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in pre-ecalmpsia. METHODS: From June 2007 to January 2008, 73 women with pre-eclampsia who delivered in the Department of Obstetrics, Affiliated Hospital of Qingdao University Medical College, were recruited, including 35 women with mild pre-eclampsia (MPE group) and 38 women with severe pre-eclampsia (SPE group). And 45 healthy pregnant women were taken as control group. Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma concentrations of oxLDL in these women. Semiquantitative RT-PCR and Western blot were used to investigate the expression of LOX-1 mRNA and protein in placenta. The expression of caspase-3 mRNA in placenta was determined using Semiquantitative RT-PCR. RESULTS: (1) The plasma concentrations of oxLDL in MPE group (0.42 +/- 0.11) mg/L, SPE group (0.68 +/- 0.12) mg/L, were significantly higher compared with control group (0.35 +/- 0.14) mg/L (P < 0.01) and the concentrations of oxLDL in MPE group were significantly higher compared with SPE group (P < 0.01). (2) The expression of LOX-1 mRNA in placenta of MPE group (0.70 +/- 0.10) and SPE group (0.84 +/- 0.08) were significantly higher than that in control group (0.58 +/- 0.11) (P < 0.01) and the expression of LOX-1 mRNA in MPE group was significantly higher than that of SPE group (P < 0.01). (3) The expression of LOX-1 protein in placenta of MPE group (0.79 +/- 0.15) and SPE group (0.90 +/- 0.12) were significantly higher compared with control group (0.68 +/- 0.11) (P < 0.01), while the expression of LOX-1 protein of MPE group was significantly higher compared with SPE group (P < 0.01). (4) The expression of caspase-3 mRNA in placenta of MPE group (3.82 +/- 0.18) and SPE group (5.39 +/- 0.14) were significantly higher than that in control group (2.19 +/- 0.20) (P < 0.01), and the expression of caspase-3 mRNA in MPE group was significantly higher than that of SPE group (P < 0.01). (5) In pre-eclampsia groups, the levels of LOX-1 mRNA in placenta were positively correlated with the plasma concentrations of ox LDL (r = 0.93, P < 0.05), and caspase-3 mRNA expression were positively correlated with the expression of LOX-1 mRNA in placenta (r = 0.84, P < 0.05). CONCLUSION: Increased levels of oxLDL in plasma may induce excess expression of LOX-1 in placenta, which may be involved in the pathophysiological processes of pre-eclampsia.

[Correlation of retinol binding protein 4 expression in maternal serum and subcutaneous adipose tissue with insulin resistance in gestational diabetes mellitus.].

OBJECTIVE: To investigate the expression of retinol binding protein 4 (RBP-4) in maternal serum and subcutaneous adipose tissue and its relationship with insulin resistance (IR) in gestational diabetes mellitus (GDM). METHODS: From May 2008 to April 2009, 62 pregnant women who underwent elective cesarean section in the Department of Obstetrics, Affiliated Hospital of Qingdao University Medical College, were recruited, including 32 with GDM (GDM group) and 30 with normal glucose tolerance test (control group). Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum concentrations of RBP-4 and radio immunoassay to measure the serum levels of fasting insulin (FINS). Fasting plasma glucose (FPG) was tested by glucose oxidase, and the Home model insulin resistance index (HOMA-IR) was calculated. Reverse transcription PCR (RT-PCR) and Western blot were applied to investigate the expression of RBP-4 mRNA and protein in subcutaneous adipose tissue. The correlations between the expression of RBP-4 mRNA and protein in subcutaneous adipose tissue and the serum RBP-4 concentrations and HOMA-IR were analyzed. RESULTS: (1) The serum concentrations of RBP-4, FINS, FPG, HOMA-IR in GDM group were significantly higher compared with the control group [(27.0 +/- 1.2) mg/L vs. (19.4 +/- 1.8) mg/L, (12.1 +/- 1.4) mU/L vs. (8.3 +/- 0.8) mU/L, (5.3 +/- 0.9) mmol/L vs. (4.1 +/- 0.6) mmol/L, 2.5 +/- 0.2 vs. 1.5 +/- 0.1, P < 0.05, respectively]. (2) The expression of RBP-4 mRNA and protein in subcutaneous adipose tissue in the GDM group were significantly higher than that of the control group (0.76 +/- 0.12 vs. 0.53 +/- 0.06, 0.74 +/- 0.09 vs 0.54 +/- 0.06, P < 0.05). (3) In the GDM group, the expression of both RBP-4 mRNA and protein in the subcutaneous adipose tissue were positively correlated with HOMA-IR (r = 0.575 and 0.851, P < 0.05). The serum concentration of RBP-4 were also positively correlated with HOMA-I (r = 0.635, P < 0.05). No correlations was found between the expressions of RBP-4 mRNA and protein in subcutaneous adipose tissue with the serume RBP-4 concentrations. CONCLUSION: High expression of RBP-4 mRNA in subcutaneous adipose tissue and the elevation of serum RBP-4 levels in GDM women may contribute to IR.

[Expression and significance of Rho-associated protein kinase II in preeclamptic placenta and umbilical artery].

OBJECTIVE: To investigate the expression and significance of Rho-associated protein kinase II (Rock II) in preeclamptic placenta and umbilical artery. METHODS: Semiquantitative RT-PCR and Western blot were used to investigate the expression of Rock II mRNA and Rock II protein in placenta and umbilical artery from 35 women with moderate preeclampsia (MPE group), 38 women with severe preeclampsia (SPE group) and 45 normal third trimester pregnant women (control group), the S/D value of umbilical artery was examined by ultrasound. RESULTS: (1) The expression of Rock II mRNA of placenta in MPE group (0.82+/-0.14) and SPE group (0.93+/-0.13) were significantly higher than that in control group (0.70+/-0.12, P<0.01). The expression of Rock II protein of placenta in MPE group (0.79+/-0.15) and SPE group (0.92+/-0.12) were significantly higher compared with control group (0.68+/-0.11, P<0.01). The expression of Rock II mRNA and protein of placenta in SPE group were higher compared with MPE group (P<0.01). (2) The expression of Rock II mRNA of umbilical artery in MPE group (0.69+/-0.13) and SPE group (0.55+/-0.12) were significantly lower than that in control group (0.76+/-0.10, P<0.01). The expression of Rock II protein of umbilical artery in MPE group (0.68+/-0.10) and SPE group (0.51+/-0.12) were lower compared with control group (0.75+/-0.13, P<0.01). The expression of Rock II mRNA and protein of umbilical artery in SPE group were significantly lower compared with MPE group (P<0.01). (3) There were no correlations between the expression of Rock II mRNA and protein in placenta and umbilical artery and the S/D value and birth weight (P>0.05). CONCLUSION: The upregulated expression of Rock II in placentas and downregulated expression in umbilical artery may be a compensation in preeclampsia.

[Relationship between tyrosine phosphorylation and protein expression of insulin receptor substrate-1 and insulin resistance in gestational diabetes mellitus].

OBJECTIVE: To study the relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor substrate-1 (IRS-1) and insulin resistance in patients with gestational diabetes mellitus (GDM). METHODS: IRS-1 expression and TP in skeleton muscle tissue were determined by Western blot and immunoprecipitation in women with GDM (GDM group, n=22), normal pregnant women (normal pregnancy group, n=22) and normal nonpregnant women (normal nonpregnant group, n=13). Fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by oxidase assay and immunoradioassay. RESULTS: (1) The levels of FPG, FINS, and insulin resistance index were calculated according to homeostasis model assessment [HOMA-IR; (5.6 +/- 0.8) mmol/L, (15.4 +/- 5.1) mU/L, and 1.2 +/- 0.5] in GDM group were significantly higher than those in normal pregnancy group [(4.4 +/- 0.5) mmol/L, (10.6 +/- 3.1) mU/L, and 0.8 +/- 0.3; P<0.01]. The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal nonpregnant group [(7.6 +/- 2.3) mU/L and 0.5 +/- 0.3; P<0.01]. (2) The level of IRS-1 protein expression in GDM group (0.64 +/- 0.11) was lower than that in normal pregnancy group (0.81 +/- 0.13; P<0.01). (3) TP with and without insulin stimulation (0.48 +/- 0.14, and 0.35 +/- 0.12) decreased in GDM group, compared with normal pregnancy group (0.66 +/- 0.12, and 0.38 +/- 0.13; P<0.01). TP with insulin stimulation in normal pregnancy group was lower than that in normal nonpregnant group (0.85 +/- 0.09; P<0.01). (4) Protein expression and TP with insulin stimulation of IRS-1 was negatively related to HOMA-IR in GDM group (r=- 0.613, -0.632; P<0.01), and TP with insulin stimulation was negatively related to HOMA-IR in normal pregnancy group (r=-0.526, P<0.05). CONCLUSION: Changes in protein expression and tyrosine phosphorylation of IRS-1 in skeletal muscle may be one of the molecular mechanisms leading to insulin resistance in patients with GDM.

[Predictive value of serum soluble fms-like tyrosine kinase 1 concentration in preeclampsia at second trimester].

OBJECTIVE: To explore the predictive value of serum soluble fms-like tyrosine kinase-1 (sFlt-1) and vascular endothelia growth factor (VEGF) levels in preeclampsia at second trimester. METHODS: Serum sFlt-1, VEGF concentrations were determined in 172 initial normal pregnant women at 26 - 28 gestation week. The outcomes of pregnancies were followed. In a cohort of 172 pregnant women, 16 cases of preeclampsia were developed (preeclampsia group), and 156 cases were with no complication (control group). RESULTS: The serum levels of sFlt-1 in preeclampsia group (11.4 +/- 6.2) microg/L were significantly higher than that in control group (4.5 +/- 2.1) microg/L (P < 0.01). The serum levels of sFlt-1 in precelampsia women with the onset before 32 gestation week and fetal growth retardation, (14.0 +/- 6.8) microg/L, (14.4 +/- 6.7) microg/L were significantly higher than that in women with the onset after 32 gestation week and with no fetal growth retardation (9.0 +/- 4.1) microg/L, (8.9 +/- 4.0) microg/L, respectively (P < 0.05). There was no significant difference in the serum levels of VEGF between preeclampsia group and control group. A sFlt-1 cutoff value of 8.75 microg/L at 26 - 28 gestation week yielded a sensitivity of 87.5%, specificity of 97.4%, positive predictive value of 80.0%, negative predictive value of 88.5%, respectively, for subsequent onset of preeclampsia. CONCLUSION: Maternal serum sFlt-1 concentration at second trimester can be used as an early predictive marker of preeclampsia.

[Expression and significance of soluble fms-like tyrosine kinase 1 in preeclampsia placenta].

OBJECTIVE: To investigate the expression and significance of serum soluble fms-like tyrosine kinase 1 (sFlt-1) in preeclampsia placenta. METHODS: Immunohistochemistry and semi-quantitative RT-PCR were used to investigate the expression of sFlt-1 and sFlt-1 mRNA in placenta of 30 women with preeclampsia (including mild and moderate preeclampsia 11 cases, severe preeclampsia 19 cases) and 45 normal pregnant women (including first trimester pregnancy 18 cases, 2nd trimester pregnancy 12 cases, and 3rd trimester pregnancy 15 cases). The levels of vascular endothelial growth factor (VEGF) and sFlt-1 in serum were detected by enzyme linked immunosorbent assay. RESULTS: (1) The expression of sFlt-1 mRNA was significantly higher in preeclampsia group (0.90 +/- 0.11) compared with the third trimester group (0.80 +/- 0.06; P < 0.01), and was higher in the severe preeclampsia group (0.93 +/- 0.12) than that in the mild group (0.85 +/- 0.05; P < 0.05). (2) The mean density of sFlt-1 in preeclampsia placenta (0.156 +/- 0.008) was significantly higher than that in the third trimester group (0.143 +/- 0.009, P < 0.01), and was higher in the severe group (0.159 +/- 0.008) than in the mild group (0.151 +/- 0.005; P < 0.05). (3) The level of VEGF in serum of the preeclampsia group (19.3 +/- 2.9) ng/L was significantly lower than that of the third trimester group [(30.2 +/- 3.1) ng/L, P < 0.01]. The level of sFlt-1 in serum of the preeclampsia group (30.2 +/- 13.7) microg/L was significantly higher than that of the third trimester group [(7.4 +/- 3.1) microg/L, P < 0.01]. (4) There was significant correlation between the serum level of sFlt-1 and the expression of sFlt-1 mRNA or sFlt-1 in placenta of normal pregnancy group (r = 0.314, P < 0.05; r = 0.439, P < 0.01) and preeclampsia groups (r = 0.372, r = 0.383; P < 0.05). CONCLUSION: Upregulation of sFlt-1mRNA and excess expression of sFlt-1 in placenta may induce higher level of sFlt-1 in serum, which may be involved in the pathophysiological processes of preeclampsia.

[Expression of matrix metalloproteinase-9 and tumor necrosis factor-alpha in the placenta of patients with pregnancy-induced hypertension].

OBJECTIVE: To investigate the role of matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of pregnancy-induced hypertension (PIH). METHODS: The placenta samples were collected from 57 patients with PIH and 24 normal pregnant women. Immunohistochemical staining was used to examine positive expression of MMP-9 and TNF-alpha in these samples. RESULTS: The positive expression of MMP-9 in the normal group was significantly higher than that in patients with moderate or severe PIH (P<0.01), while no significant difference was found between normal pregnant women and patients with mild PIH (P>0.05), and expression decreased drastically with the progression of PIH (P<0.05). The expression of TNF-alpha in the patients with mild, moderate and severe PIH groups were significantly higher than that in the normal group (P<0.05, P<0.01 and P<0.01, respectively), and the differences were also significant between the PIH groups of different severities (P<0.01). No correlation was found between MMP-9 and TNF-alpha expressions in the normal and mild PIH groups (r=0.287, P>0.05; r=0.382, P>0.05), in the patients with moderate and severe PIH, MMP-9 expression showed inverse correlation with TNF-alpha expression (r=-0.563, P<0.05; r=-0.681, P<0.01). CONCLUSION: Lowerd MMP-9 expression in syncytiotrophoblast might result in defective nidation in the placenta where local ischemia and hypoxia cause abnormal TNF-alpha elevation, which might be one of the important factors inducing PIH.