A Study On The Correlation Between HGF/C-met HIF-1α And The Pathogenic Of Hypertensive Disorder Complicating Pregnancy

Objective: To evaluate the changes of the levels of HGF/ C-met HIF-1αin placenta of patients with hypertensive disorder complicating pregnancy, and the correlation between HGF/ C-met and HIF-1. It would provide a new train of thought for further study of the pathogeny.Methods:1 The study subject1.1 The study group: 40 patients with preeclampsia (PE group, 20 patients with severe preeclampsia and 20 patients with mild preeclampsia were involved ) who had prenatal examinations and delivered in the Obstetrics of the Second Hospital of HeBei Medical University were selected from November 2005 to July 2006. Mean age of them was 27.68±3.06 years old (24 to 33 years old), and mean gestational age was 35.26±2.16(32 to 40 weeks of gestation). Diagnosis criteria of severe preeclampsia was: blood pressure≥160/110mmHg; proteinuria≥2.0g/24 hours or proteinuria of (++); serum creatinine>106μmol/L; platelet count<100×109/L; microangiothic hemolysis (elevation of serum LDH); elevation of serum ALT or AST; persistent headache or other disturbances of cranial nerve or vision; persistent discomfort of the epigastrium. Diagnosis criteria of mild preeclampsia was: blood pressure≥140/90 mmHg after 20 weeks of gestation; proteinuria≥300mg/24 hours or proteinuria of (+) ; accompanying with symptoms of epigastric discomfort or headache.1.2 The control group: 20 health third trimester pregnant women were select to serve as the control group .Mean age of them was 27.31±2.61years old (23 to 35 years old );and mean gestational age of them was 36.98±1.34weeks(36 to 40 weeks). all the subject must meet the following criteria: no multi gestations, no chronic hypertension, no diabetes, no heart disease, no chronic renal disease, no chronic liver disease and no immune disease.2 Sample collecting: About 1cm3 placental tissues were collected from the pregnant women after the placental was deliveried. Use axenic 0.9% sodium chloride to wash it and fix it with formaldehyde.3 The experiment methods: Use H and E method and immunohistochemical method to determine the level of HGF/C-met and HIF-1α.To analyze the results by means of the SPSS 13.0.Results:1 The expression position of HGF, C-met in placenta: they were all expressed in the cell nucleus and cell liquid of the syncytiotrophocyte cells and the cell cytotrophoblastic cells in placenta. They also were expressed in the liquid of chorial blood capillary cells in placenta. The expression of HGF and C-met is concomitant.2 The expression position of HIF-1αin the placenta:HIF-1αwas expressed in the liquid of the syncytiotrophocyte cells and the cell cytotrophoblastic cells in placenta.3 The expression and comparision of HGF and C-met in the preeclampsia group and the healthy pregnant group in placenta: the expression in the study group was markedly statistical difference when the severe preeclampsia group compared with the control group (P<0.05) , but there was no statistical difference between the mild preeclampsia group (P>0.05).4 The expression and comparision of HIF-1αin the placenta: Compared with the study groups and the control group, the HIF-1αexpression was significantly higher than those in the control group. It was statistical difference when the severe preeclampsia group compared with the control group (P<0.05), there was markedly statistical difference between the mild preeclampsia group and the control group (P<0.05).5 The correlation between HGF/c-met and HIF-1α: there was a negative correlation between the expression of HGF/c-met and HIF-1α(P<0.05)in the preeclampsia groups.6 The correlation between the density of chorial blood vessel and HGF: was a positive correlation between them (rs =0. 499 P<0.05); The correlation between the number of chorial trophoblastic cells knots and HGF: was a negative correlation between them(rs = - 0.38 P<0.05)7 The correlation between the number of chorial trophoblastic cells knots and HIF-1α: was a positive correlation between them(rs = 0.794 P<0.05)8 The correlation between HGF and diastolic blood pressure of the study group: was a negative correlation between them(rs = -0.699 P<0.05)9 The correlation between HGF and systolic blood pressure of the study group: was a positive correlation between them (rs = 0.749 P<0.05)Conclusion:1 In the study we found that the correlation between the number of chorial trophoblastic cells knots and HGF: was a negative correlation between them. the study group was markedly increased compared with the healthly pregnancy group (P<0.05).We presumed that the invasion biology of the trophoblastic cell was regulated and controlled by the expression of HGF. The abnormal expression of HGF will lead to depress the amount of and the invasion ability of the trophoblastic cells, and may restrain the corrosion of trophocyte.2 In the study, It was found that HIF-1αand c-met have the common binding sites on the gene level. HIF-1αcan assist c-met to educe the effect of promoting generation in placenta trophoblastic cell. Although the lower expression of c-met in preeclampsia group, it was significantly effect of HIF-1αto promote generation in placenta trophoblastic cell.3 In the study, it is found that the expression of HGF was significantly lower in preeclampsia group than in the control group. The density of chorionic blood vessels was also lower. We presumed that the lower expression of HGF was the key factor to dyspoiesis in placental villus blood vessel. The abnormal expression of HGF may significantly effect the placental villus blood vessel re-casting.4 There was a negative correlation between the expression of HIF-1αand HGF/c-met in the study groups and the control group.5 In the study ,we found that HGF can adjust the biological activities of trephocyte multiplication,infiltration,differentiation and invasion by trephocyte signal transduction pathway to the explain theory of placenta light nidation. The abnormal expression of HGF in placenta may serious effect the biological activities of trephocyte, promote the pathogenetic condition (hypertensive disorder complicating pregnancy) development.6 In the study, we found that HGF and HIF-1αcan product two group antistatic cytokines of vascular endothelial cell by adjusting the trephocyte signal transduction pathway. It was imbalance of the cytokines in the study groups, which may induce a series of typical clinical situations of hypertensive disorder complicating pregnancy. Such as hydrops,hyperpiesia,proteinuria. 7 Now the function of HGF was gradually to be thought highly of in the therapia of hypertensive disorder complicating pregnancy. HGF has become one of the significant cytokines to progress the intervention therapic, which may be a new assistant method to treat hypertensive disorder complicating pregnancy.