Font Size: a A A

Study On The Level Of Inositol 1,4,5 Trisphosphate (IP3)receptor(IP3R) In Placenta Of Normal Pregnancy And Hypertensive Disorders In Pregnancy

Posted on:2010-12-22Degree:MasterType:Thesis
Country:ChinaCandidate:H X SunFull Text:PDF
GTID:2144360272997454Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Objective: Hypertensive disorders in pregnancy (pregnancy-induced hypertension ) is a unique disease to pregnancy. This disorder is still one of the leading causes of increasing of maternal and fetal morbidity and mortality . Therefore, the research on the cause and the pathogenesis of pregnancy-induced hypertension has been an important subject of obstetrics. With in-depth research, more and more study inclined to the correlation between the occurrence of pregnancy - induced hypertension and calcium imbalance in pregnant women's body, disorders of energy metabolism and endothelial cell activation. Calcium is the intracellular messenger of signal transduction. Its any change in the channels generating energy will result in a series of pathological phenomena.As one of the two major calcium release family in cell, intracellular calcium release mediated by inositol trisphosphate receptor(IP3R) is very important to the regulation of the intracellular calcium concentration. IP3R is a cell signal transduction molecule be increasingly concerned in recent years and IP3 can be changed in many pathological conditions.At present there is a great deal of research about IP3R in cardiovascular disease, however ,most of the research is limited in animal experiments in vitro and the establishment of disease model because the difficulties in obtaining organizations such as smooth muscle etc. The research on hypertensive disorders in pregnancy which is specific in pregnancy and can cause systemic changes in the various systems is rare. The placenta is a vital organ of the fetus to obtain nutrients from the mother and exclusive metabolites,which has two separate circulatory system consisted of the maternal and descendant's. The detection of the expression of IP3R may response the maternal situation indirectly. The collection of specimen is convenient.In this paper, we collect placenta randomly from the normal pregnant women and the patients with hypertensive disorders in pregnancy of mild and severe pre-eclampsia without complications. Then we detect the allocation and expression of IP3R in the placenta of patients with hypertensive disorders in pregnancy by immunohistochemistry, analyze the relation between the signal transduction pathway and pregnancy-induced hypertension-related diseases, and explore the role of calcium signal mediated IP3R in the hypertensive disorders in pregnancy. In order to provide proof for the cause and pathogenesis of pregnancy-induced hypertension disease and the new targets of its treatment , reduce the incidence and mortality of pregnancy-induced hypertension, improve their cure rate and reduce premature delivery, fetal growth restriction, fetal distress, neonatal asphyxia and the occurrence of placental abruption. The further study of this signal transduction pathway may develop a new way of thinking for resolving the pathological mechanism of the hypertensive disorders in pregnancy.Method: Placental tissue samples were collected from 40 healthy pregnant women as a control group and 80 patients composed of 40 mild preeclampsia and40 severe preeclampsia as tested groups. All specimens came from the Second Clinical Medical Hospital of Jilin University (2006--2008). All of the patients had no complications. There were no significant differences in age and gestational weeks among 3 groups. After delivery, rapid disposal placenta including maternal and fetal surface(avoid calcified lesions) about 1.0cm×0.5cm×0.5cm, then 10% formalin-fixed, paraffin-embedded conventional. After enough specimen were collected, slice together, then immunohistochemical method (SM avidin- peroxydase) was used to detect the density of expresstion of IP3R protein. Experimental steps were carried out in accordance with the operating instruction of the reagent.Result's standard: Observing results made use of double blind procedure .The positive expressions showed brown particles in cytoplasm or nucleus inferior mirror lens. Refer to Hao's comprehensive scoring method: observe the distribution, positive strength and positive rate of IP3R protein. First according to the degree of stain score zero, one, two and three respectively. The degree of stain must be relative ratio to the background color. Second according to percent of positive cell score zero(<5%﹚,one(5%~35%),two(36%~65%),three(>65%) respectively. When half of the sum of percent of positive cell and degree of stain is <0.5,response to immunization is negative , 0.5~1 is positive , 1.5~3 is strongly positive. Choose one microtome section per specimen and five campus visualis per microtome section. Use software SPSS11.5 to analyze results of immunohistochemistry and make use of rank-sum test to compare rate among these groups. Take P value below 0.05 as significance difference.Results: The distributions of IP3R in placenta tissues among three groups were conformity. IP3R is mainly distribute in the trophoblast cells and decidual tissue, next the positive cell also could be observed in endothelial cell of capillary and part of stroma. The expression of IP3R in patients with mild preeclampsia were significantly higher than those in normal pregnant women and the difference was statistically significant (P<0.05). With the advanced of the disease, IP3R's expression gradually increased. IP3R's expression intensity of severe pre-eclampsia was significantly higher than that of mild pre-eclampsia group, the difference was statistically significant (P <0.05).conclusion:1. The distribution ofy IP3R in the normal placenta tissue demonstrate that there is a very close relationship between the synthesis, secretion of IP3R and the physiology of normal pregnancy.2. The expression of IP3R in pre-eclampsia group was significantly higher than the normal pregnancy group. The difference between the two groups was statistically significant (P <0.05), which may hint that the increased expression of IP3R during pregnancy has an influence on the function of vascular endothelial cells and trophoblast cells, which is concerned with the occurrence and development of pre-eclampsia and eclampsia. 3. There was a trend that the density of expression of the IP3R increased with the severity of disease .The density of expression of IP3R by immunohistochemical method reflects the severity of pre-eclampsia at a certain extent.4.The research detect the expression of the IP3R in placenta of the hypertensive disorders in pregnancy is the first in domestic and overseas, hint the signal transduction pathway have obvious dependability to the desease.In the future we will research it in the molecular level ,which will provide a new path for the prevention of pregnancy-induced hypertension disease,decrease the nosogenesis,develop of it and reduce premature delivery, fetal growth restriction, fetal distress, neonatal asphyxia and the occurrence of placental abruption.
Keywords/Search Tags:Inositol trisphosphate receptor, Preeclampsia, Placenta, Hypertensive disorders in pregnancy
PDF Full Text Request
Related items