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The Expression Of HO-1 And HIF-1α On Preeclampsia Of Hypertensive Disorders Complicating Pregnancy

Posted on:2010-03-18Degree:MasterType:Thesis
Country:ChinaCandidate:X Y HuoFull Text:PDF
GTID:2144360275969819Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Objective: Preeclampsia is a significant health problem of pregnancy, affecting approximately 9.4%~10.4% of women in china. As preeclampsia is associated with increased maternal, perinatal and neonatal morbidity and mortality. Heme Oxygenase-1 is a kind of antioxidative enzyme, which catalyzes the rate-limiting oxidation of heme to the biologically active molecules biliverdin and bilirubin, releasing iron and carbon monoxide in the process. It is expressed at a low level in most mammalian tissues and is highly induced by many factors which induce oxidative injury such as heme, hydrogen peroxide, ultraviolet radiation, heavy metals, hypoxia, hyporoxia, nitric oxide(NO),shear stress, endotoxin, cytokines, growth factors et al and protect against oxidative stress. It is found that HO-1 could protect people from a lot of diseases and its protective mechanism relates undoubtedly to various kinds of metabolites produced in catabolism, but the exact mechanism remains unknown. Hypoxia-inducible factor-1 alpha (HIF-1α) is an important regulator of the responses of a cell to oxygen tension. HIF-1αis a widely expressed basic helix-loop-helix (bHLH)-PAS transcription factor composed of two subunits: HIF-1αand HIF-1β. This family is responsible for mediating the response of cells and organisms to various environmental stimuli, including xenobiotic exposure, hypoxia and light. Immunohistochemical staining was used to examine negative expression of HO-1 and positive expression of HIF-1αin these samples. It elucidate the possible relationship between HO-1/ HIF-1αexpression and the pathogenesis of preeclampsia. To investigate the expression of HO-1 and reduce the HIF-1αin placental of women with preeclampsia and normal pregnancy is sufficient.Method: Placental samples were obtained in 10 minutes after delivery from 30 normal pregnancy women and 30 patients with mild preeclamptic pregnancies, 15 with severe preeclampsia. The villi were taken from them. All placentas were obtained from women undergoing spontaneous labor when they took on caesarean surgery. All tissues were routinely fixed in 10 percent formalin and embedded in paraffin. Five-μm-thick tissue sections of all samples were stained by immuno- histochemical analysis. Statistical analyses were performed with the use of the SPSS 13.0. Kruskal-Wallis H test and spearman rank correlation were used to analyze the data,α<0.05 was considered statistically significant.Result: 1The three groups were matched in maternal age, parity and gestational age. 2 In the study, HO-1 was localized to placental trophocyte cells and mesenchymal cells. The concentrations of immunoreactive HO-1 on normal placental trophocyte cells and mesenchymal cells were strongest, positive rate was 83.33% and that of severe preeclampsia were almost negative, positive rate was 33.33%, mild preeclampsia had stronger expression, positive rate was 66.67%(showed by Fig.1, 3-5, table 1). The difference between the normal placenta and preeclamptic placenta was statistically significant (P<0.05); the difference between the normal placenta and severe preeclamptic placenta was statistically significant (P<0.01); the experiments found significant differences in HO-1 by severe and mild preeclampsia placenta (P<0.05); no difference was found between normal and mild preeclampsia placentas (P>0.05). 3 HIF-1αwas localized to placental trophoblast cells. The expression of HIF-1αon control group was the weakest, positive rate was 30.00%, and that of severe pre-eclampsia was almost negative, positive rate was 86.67% ,mild preeclampsia had weaker expression, positive rate was 63.33%(Showed by Fig.2, 6-8, table 2). The difference between the normal placenta and preeclamptic placenta was statistically significant (P<0.05); the difference between the normal placenta and severe preeclamptic placenta was statistically significant (P<0.01); the experiments found significant differences in HIF-1αby severe and mild preeclampsia placenta (P<0.05); no difference was found between normal and mild preeclampsia placentas (P>0.05). 4 No correlation was found between HO-1 and HIF-1αexpressions in normal and mild preeclampsia groups (r=0.232 p>0.05; r=0.225 p>0.05), in patients with severe preeclampsia, HO-1 expression showed negative correlation with HIF-1α expression (r=-0.365,p<0.01).Conclusion: Based on the data mentioned above, we can come to the following conclusions: 1 Placental villi can express HO-1 and HIF-1αmainly on trophoblast. 2 HO-1 and HIF-1αmay play an important role in placental trophoblast invasion. Decreased expression of HO-1 and (or) increased HIF-1αmay affect acquisition of an invasive by trophoblasts, resulting in the abnormal shallow trophoblast invasion of the uterus that is associated with preeclampsia. 3 negative correlation was found between HO-1 and HIF-1αexpression in severe preeclampsia placenta and normal placenta.
Keywords/Search Tags:Heme Oxygenase-1, Hypoxia-inducible factor-1α, Hypertensive disorders complicating pregnancy, Preeclampsia, Placenta
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