Tissue Levels Of Advanced Oxidation Protein Products In Preeclampsia And Its Significance

BackgroundsPreeclampsia is a peculiar disease during pregnancy, in our country the incidence is about9.4%-10.4%. Preeclampsia severely affected the maternal and child health, preeclampsia is one of the main reasons of maternal and perinatal morbidity and mortality. Preeclamsia is a disease which occours after20weeks gestation firstly, characterized by proteinuria, edema and hypertension; and systemic multiple organ damage, seriously patients may be lead to convulsions, coma, cerebral hemorrhage, pulmonary edema, heart failure, disseminated intravascular bleeding and death; the incidence of fetal growth restriction and preterm birth in preeclampsia is much higher than that of normal pregnancy women. The preeclampsia is multifactorial causes, at present the disease pathogenesis is not yet clear. The current clinical treatment meathod mainly is symptomatic and termination of pregnancy. Due to the lack of a predictive means and control means, make the disease become the second reason which leading to maternal death, and is the leading cause of maternal and perinatal morbidity. Now many scholars believed that preeclampsia disease correlated to several factors:abnormal trophoblast cells invade the myometrium, immune injury, vascular endothelial cell injury, genetic factors, nutritional deficiency and insulin resistance, and the vascular endothelial cell dysfunction and oxidative stress are closely related. Some studies suggestted that oxidative stress may be play a key role in preeclampsia. Many scholars have found that in preeclampsia the imblanace between oxidant and antioxidant system is destructed, and the total balance tend to oxidation stress.Placental morphology and function changing appeared before clinical symptoms in preeclampsia, and the clinical symptoms and clinical signs disappeared quickly after delivery of the placenta, these show that the placenta may play a key role in the process of preeclampsia. At present, some scholars suggestted that preeclampsia is a derived placental disease, its maybe originated from abnormal placental trophoblast invasion and placental oxidant and antioxidant imbalance, which can lead to inflammatory cytokines release, the involvement of endothelial injury, caused further systemic endothelial dysfunction, resulting in vasoconstriction, end-organ hypoperfusion, vascular permeability increased, which will lead to preeclampsia clinical symptoms.Oxidative stress plays a key role in many endothelial dysfunction diseases. Many researches proved that the excessive products of lipid peroxidation and antioxidant system’s function decreased result in oxidative stress. Literatures have reported that the circulating products of lipid peroxidation of preeclamptic patient increased compared to normal pregnant women. Uncontrollable peroxide may cause intimal lipid and other cell fractions ablation. The feature of oxidative stress is the high concentrations of ROS. The expression of free radicals and reactive oxygen species in preeclampsia is increased, and antioxidant system’s function declined, make the body in oxidative stress stutas. Of course, in normal pregnant women also saw the free radical production increased, but as a result of pregnancy antioxidant capacity increased, the patients do not constitute oxidative stress. Proteins, peptides and amino acids are sensitive on free radicals. In preeclampsia patients, oxidation products increased (such as, lipid peroxide, protein oxidation products and nucleic acid oxidation products), as the same time the preeclampsia antioxidant capacity weakened, resulting in oxidative stress status in preeclampsia. In addition because of the placenta ischemis, hypoxia, procuded a large number of free radical generation, lipid, protein oxidation, endothelial cell injury; these cause the oxidative stress process aggravated, leading to disease development.Advanced oxidation protein products (AOPP) is a novel protein oxidative stress marker, they are the end products formed between oxidative stress and protein. It is firstly found in plasma of chronic renal failure patients by Witko-Sarsat. At present, many studies have found that AOPP is a reliability maker of protein oxidation degree, it contained of tyrosine cross-linking, it is componed of serum albumin reactioned with free radicals and reactive oxygen system (mainly neutrophil myeloperoxidase generates chloride oxide). In vitro, experiments found that AOPP can lead to human vein endothelial cell injury, release of inflammatory factor, further aggravating the degree of oxidative stress. The expression levels of AOPP are increased in diabetes, atherosclerosis, coronary heart disease, uremia, chronic enteritis and other diseases. Hideaki Kaneda studies showed that plasma protein occurred oxidation in chronic coronary disease and uremic disease. The levels of AOPP increased both in uremic patients and patients with chronic coronay artery disease. Oxidative stress may be related with the pathology of chronic coronary disease. Agnieszka Piwowan showed that diabetes mellitus is a complex metabolic disorder disease induced by exccesive ROS and antioxidant system imbalance, its TRAP and SH levels decreased, at the same time the level of CO, NH2and AOPP increased. AOPP levels in type Ⅱ diabetes increased significantly. The AOPP may be a useful marker which used to assesse oxidant mediated protein damage in diabetes mellitus patients. AOPP is not only the product of oxidative stress, but also cause monocyte neutrophil respiration burst, induce monocytes to produce more reactive oxygen species, positive feedback oxidative stress response, so that the body showed a persistent oxidative stress status.At present, there is little research about AOPP in normal pregnant women and preeclampsia both in domestic and foreign. There is no research reported about the AOPP level in umbilical cord, placenta tissues of preeclampsia. And there are many differents between domestic patients and the foreigners, such as dietary habits, environmental, genetic and other factors, these factors may effect the AOPP levels between the two groups. In this paper, through the observation the expression of advanced oxidation protein products (AOPP) in umbilical cord and placenta tissues of 26examples of preeclampsia patients (including mild preeclampsia of10cases, severe preeclampsia of16cases) and20cases of normal pregnancy, discussed the correlation between AOPP and oxidative stress status; and further explored its role in the process of preeclampsia.ObservationDetermination the differences expression of AOPP in umbilical cord and placenta tissues in preeclampsia and normal pregnancy, discussed the correlation between AOPP and preeclampsia, exploring its role in pathogenesis of preeclampsia, provided clues for further study of oxidative stress in the pathogenesis of preeclampsia molecules pathways.Research methods1、Using the immunohistochemical method for the detection of umbilical cord AOPP expression levels of patients with preeclampsia and normal pregnancy, and whether there are differences;2、Using the immunohistochemical method for the detection of placental AOPP expression levels of preeclampsia patients and normal pregnancy, and whether there are differences;3、Used the average gray density expression the AOPP level in umbilical cord and placenta.4、Statistics using SPSS13.0software, Statistical differences between means for different groups were evaluated using Independent-Samples T Test and One-way ANOVA (Levene’s-test, SNK-test and Welch-test). P<0.05difference has statistics significance.Results1、A statistically significant increasing in the expression of AOPP were found in both mild and severe preeclampsia umbilical cord, compared to normal control umbilical cord,(P<0.05),. The AOPP quartity had good correlation with the severity of preeclampsia (P<0.05).2、A statistically significant increasing in the expression of AOPP were found in both mild and severe preeclampsia placenta, compared to normal control placenta,(P<0.05),. The AOPP quartity had good correlation with the severity of preeclampsia (P<0.05).Conclusions1、A statistically significant increasing in the expression of umbilical cord AOPP were found between preeclampsia patients and normal pregnancy.2、A statistically significant increasing in the expression of placenta AOPP were found between preeclampsia patients and normal pregnancy.3、AOPP expression levels of umbilical cord and placenta in preeclampsia has position correlation with the severity of the disease.4、These findings showed that the increased AOPP is the most important pathological of preeclampsia, which may be involved in the occurrence and development of preeclampsia.