Expression And Significance Of The Differently Expressed Protein In Serum From Patients With Hypertensive Disorder Complicating Pregnancy

Objective:Hypertensive disorder complicating pregnancy is a kind of diseasethat severily harm the health of pregnant women and infants.It is the main cause ofpregnant women and infants'death. Althought there are many hypothesizes ,peoplecan not satisfactly interprete the pathogenesy of this diease. Because there is no satisfact therapy for this diease,it is very impormtent that to screen high risk gravida and monitori high-risk group as early as possible.But up to now there are still not specific biomarker in serum can as early scanning indicatrix. Proteomics give us a new method and strategy to study the pathogenesy and the method of early scanning hypertensive disorder complicating pregnancy.Our study apply proteome echnique to scan the serum special biomarker of hypertensive disorder complicating pregnancy. We hope we can get the serum special biomarker of hypertensive disorder complicating pregnancy and some specificness associated proteins of this disease and give us some enlightenment of pathogenesy.Method:21 patients that are hypertensive disorder complicating pregnancy and 10 normal pregnancies were tested by Weak cationic exchang (WCX2) protein chip and surface enhanced laser desorption ionization-time of flight-mass-spectrometry of Ciphergen Inc. The differentially expressed proteins were analyzed by BioMarker Wizard, set up diagnostic cast of the hypertensive disorder complicating pregnancy and severe preeclampsia by Biomark Pattern Software and obtained its positive predictive value and accuracy and specificity. Using this diagnostic cast we gave a double-blind trial to the remanent serum samples from patients with and control group to get its accuracy and specificity. At last we researched the differently expressed protein on the UniPort protein database according to their molecular weight and it was further verified by ELISAResult:1. In the rang of M/Z from 1000 to 20000 there are distinction between two groups'serum mass spectrums. In the serum of mild preeclampsia group,the relative amount of protein which M/Z is 3936 ( 2.52±1.89 ) is obviously lower than normal group (8.42±4.75) (P< 0.05 ), the relative amount of proteins which M/Z are 3263,7979 and 13773 (4.67±0.79, 24.16±15.27, 3.87±1.5) is obviously higher than normal group( 0.85±0.45, 3.23±1.21, 0.46±0.16 ) ( P< 0.05 )。2. In the rang of M/Z from 1000 to 20000 there are distinction between two groups'serum mass spectrums. In the serum of severe preeclampsia group,the relative amount of protein which M/Z is 7982 and 15943 (3.18±1.35, 2.12±1.58 ) is obviously lower than mild preeclampsia group (21.18±13.41, 18.12±10.46) (P< 0.05 ), the relative amount of proteins which M/Z are 3263 and 13773 (16.34±4.5, 9.49±0.75) is obviously higher than mild preeclampsia group (4.67±0.79, 3.87±1.5 ) ( P< 0.05 )。3. We have developed two protein profiles (3263, 13773) that can separate patients with hypertensive disorder complicating pregnancy from normal pregnancies. It gives the much-improved sensitivity of 90.48% and the specificity of 80%.4. We have developed four protein profiles (3263, 7982, 13773, 15943) that can separate patients with severe preeclampsia from patients with mild preeclampsia. It gives the much-improved sensitivity of 100% and the specificity of 87.5%.5. Through searching databases, we have got six probably significant protein related with six different protein among three groups.6. Further confirmed by ELISA, M / Z for 3263 and 13773, respectively protein VIP and MCP-1.Conclusion:1. Application of SELDI-TOF-MS technology to test serum from patients with hypertensive disorder complicating pregnancy and found six kinds of the differently expressed proteins, these proteins may participate the occurrence and development of hypertensive disorder complicating pregnancy.2. The diagnose model making use of the differently expressed proteins has a high degree of sensitivity and specificity.3. Search the database to identification of the six kinds of the differently expressed proteins, are Vasoactive intestinal peptide, Islet amyloid polypeptide, Ubiquinol-cytochrome c reductase complex 7.8 kDa protein, Ferredoxin-like, Small-inducible cytokine A2 precursor, Atrial natriuretic factor precursor.4. By ELISA found content of MCP-1 in serum from patients with hypertensive disorder complicating pregnancy to increase progressively along with disease aggravation, and prompts MCP-1 related to incidence and development of diseases.5. By ELISA found content of VIP in serum from patients with hypertensive disorder complicating pregnancy to increase progressively along with disease aggravation, and prompts VIP related to incidence and development of diseases.6. Using SELDI-TOF-MS, the method of sieving the marker from becomes quick and valid.