The Study On The Relationship Between TLR2,TLR4,Resistin And Idiopathic Fetal Growth Retriction

Fetal Growth Restriction refers to the phenomenon of which the fetal birth weight is below the two standard deviation of the average weight with gestational age,or below the loth percentile number of normal weight with gestational age,or less than 2500g after 37 weeks'gestation.It is one of the important perinatal complication.The high perinatal incidence and mortality not only lead to the influence of fatal intrauterine development but also impacts on the physical and intellectual development in childhood and adolescence. And it is one of the causes of the adolescence intrauterine disease according to the epidemiological investigation. FGR has many pathogenies and its nosogenesis is complicated.At present,there are as much as 40% patients whose pathogenies are not clear,which is called (idiopathic fetal growth restriction, IFGR).In recent years,with the fast development of immunology the research into the gestational immunomodulation has been changed from the systematic immunity deeping into the local immunity of maternofetal interface.If the immune reaction loses balance,it may influence the growth and development of fetus and placenta and lead to a negative gestation effect.Toll-like receptors is a kind of action pattern recognition receptor,At present eleven kinds of human TLRS which are expressed in many organs and tissues in the human body has been found one after another and they can identify different types of exogenous pathogens and endogeneous autacoid.TLR2,TLR4 are expressed strongly in the placenta villus and trophblast.After combined with ligands,TLR2,TLR4 can activate NF-κB through the intra-cellular MAPK signal transduction and induce various inflammatory cytokines.So as to trigger the acquired immunity reaction to defend the invasion of hazardous material by starting the innate immunity reaction so as to promote the development of fetus and placenta.If the immunomodulation reaction lose balance in the maternofetal interface,the organism can not clear hazardous materials effectively or immune reaction is excessive,or the secretion of cytokines related to the development of fetus disorders,they all may cause the nega- tive gestational effects. So it can be one of the key links of IFGR nosogenesis.The resistin is a new-found placenta hormone.The human placenta tissue can participate in the adjutstment of gestational serum resistin level.Recently,the resistin has been put forward as having a kind of characteristics of proinflammatory cytokines.It can adjust other inflammatory agents through NF-κB hedgehog.So it has the correlation with TLRs and they may participate in the IFGR nosogenesis together.At present the research into the TLR2,TLR4 and the resistin in IFGR nosogenesis has been seldom reproted.This research subject is about further discussing the proximal cause of IFGR and its possible nosogenesis from the infection and immunity aspects.ObjectiveTo discuss the expression of TLR2,TLR4 in the placenta of IFGR patient and the expression of resistin in the maternal blood,cord blood and further detect the relation among the three points mentioned above and its meaning in the IFGR nosogenesis. It is also expected to find new targets for the clinically prevention of IFGR occurrence.Methods1 subject investigated: we selected 36 cases of IFGR pregnant women in the third Affiliated Hospital of Zhengzhou University from June 2009 to June 2010 hospital deliveries,the corresponding time period of normal pregnant women (control group) 30 cases. All enrolled women were single birth,primipara,regular menstrual cycle,the last menstrual was clear.Exclusion criteria included dysfunction of the liver and kidney, pregnancy complications, uterine contraction and cesarean section deliveries.the 1th edition of gynemetrics edited for seven years by Feng Youji is adopted as the reference standards for the diagnostic criteria of FGR and IFGR.2 methods:2.1 testing methods:using immunohistochemical SP method detected TLR2,TLR4 and NF-κB expression in the placenta.Using double-antibody sandwich enzyme-linked sorbent assay method (ELISA) detected the concentration of the resistin in the fetal cord blood and maternal blood serum.2.2 statistical method:using SPSS 13.0 software packages to analyze the experimental data statistically.All the enumerationdata are showed by using (x±s),using t to test the comparison of the two enumerationdata groups,using Pearson linear correlation to analyze the two factors relativity analysis.Use a=0.05 as inspection level.Results1 the comparison of the common clinical data between the experimental group and the control group:the difference between the two groups of pregnant women in their clinical data,ages,preconception weights,gestational weeks, pragnante parities has no statistic meaning(P>0.05).the placenta weight,fetal birth weight,fetal birth stature of the experimental group are all lower than those of the control group.The difference has the statistic meaning.(P<0.05)2 The expression and relativity of TLR2,TLR4,NF-κB in the placenta of the experimental group and the control group2.1 TLR2,TLR4 protein:Both the placenta of two groups have positive expressions of different levels,the positive taking on yellow or brown are mainly positioned on syncytiophoblast of the placenta and cytoplasm. exochorial trophoblast,chorion mesenchyma and endangium are expressed a little.In the expression of TLR2,TLR4 protein in the syncytiophoblast of the placenta of the two groups,the experiment group is higher than those of the control group The difference has the statistic meaning.(P<0.05)2.2 NF-κB protein:NF-κB protein is expressed in different levels in the placenta of two groups.the positive taking on yellow or brown are mainly positioned on syncytiophoblast of the placenta and cytoplasm.The expression of NF-κB protein in the placenta of two groups, the experiment group is higher than those of the control group The difference has the statistic meaning.(P<0.05)2.3 In the experiment group, the expression level of TLR2,TLR4 protein of the placenta and the expression level of NF-κB protein existed positive correlation (P<0.05) there does not existed correlation.3 The expression and correlation of the resistin in maternal blood and cord blood in the experiment group and the control group.the expression level of the resistin in maternal blood and cord blood in the experiment group is higher than that of the control group. The difference has the statistic meaning. (P<0.05) In the experiment group, the expression level of the resistin in cord blood is higher than that of the resistin in maternal blood (P<0.05);but the the expression level of the resistin in maternal blood and cord blood has no correlation. (P>0.05)4 The correlation between the resistin level in maternal blood and cord blood and the expression level of TLR2,TLR4 of the placenta in the experiment group.In the experiment group, the resistin level of cord blood and the expression level of TLR2,TLR4 of the placenta existed positive correlation (P<0.05) the resistin level in maternal blood and the expression level of TLR2,TLR4 of the placenta has no correlation (P>0.05)Conclusions1. The expression of TLR2,TLR4 of the placenta may participate in the IFGR nosogenesis.2. The rise of the resistin level in maternal blood and cord blood may be one of the main factors of the IFGR nosogenesis.3. TLR2,TLR4 may influence the development of fetal together by adjusting the expression of the resistin.