Abnormol Expression Of HDAC3-NF-κB Signailing Pathway In Placenta With Intrahepatic Cholestasis Of Pregnancy And Its Significance

Objective Recent studies have been found that there was a close relationship beween intrahepatic cholestasis of pregnancy and immune imbalance,and HDAC3-NF-κB signalling pathway played an important role in the regulation of immune balance.To evaluate the locations and expressions of the nuclear transcription factor-KB(NF-KB),inhibitor of nuclear transcription factor-κB-α(IκB-a),histone deacetylase3(HDAC3) and acetylased-nuclear transcription factor-KB (Acetyl-NF-κB) in human placenta with intrahepatic cholestasis of pregnancy(ICP) and explore the expression and significance of HDAC3-NF-κB signalling pathway.Methods We chosed 41 ICP women as the study objects.All of them were delivered in the First Affiliated Hospital of Chongqing Medical University from May 2012 to May 2013,and divided into two groups,mild group (n=19) and severe group (n=22).Twenty healthy pregnant women who delivered in the same period were chosen as the control group (n=20).Immunohistochemical was employed to detect the localizations and expressions of NF-κB,IκB-α,HDAC3 and Acetyl-NF-KB in placenta tissue. Western blot was used to detect the NF-κB、Acetyl-NF-κB-、IκB-α and HDAC3 protein levels in the three goups.Results (1) The serum levels of alanine transferase (ALT), aspartate transferase (AST) and total bile acid(TBA) in the control group, mild proup and severe group were (17.3±4.5), (116.9±31.2), (351.3±105.3)U/L, (21.3±4.1), (105.1±28.2), (308.7±146.1)U/L, and (2.76±1.00), (22.33±10.61), (51.80±21.16)μmol/L, respectively.The ALT,AST and TBA serum levels in the control group, mild proup and severe group were gradually and significantly increased(P<0.05). (2) NF-κB was mainly located in the nucleus of placenta syncytiotrophoblastic cells in the three groups, stained light tan in control group and mild ICP group, and stained dark tan in severe ICP group. IκB-α was mainly located in the cytoplasm of placenta syncytiotrophoblastic cells in the three groups, stained light tan in severe and mild ICP group, and stained dark tan in control group. HDAC3 was mainly located in the nucleus of placenta syncytiotrophoblastic cells in the three groups, stained light tan in severe and mild ICP group, and stained dark tan in control group. Acetyl-NF-KB was mainly located in the nucleus of placenta syncytiotrophoblastic cells in the three groups, stained light tan in control group and mild ICP group, and stained dark tan in severe ICP group. (3) The NF-κB protein level in placenta of the control group, mild proup and severe group was (0.231±0.019),(0.358±0.047) and (0.550±0.006), respectively. NF-κB protein level in the the control group mild proup and severe group was gradually and significantly increased(P<0.05). The IκB-a protein level in placenta of the control group, mild proup and severe group was (0.678±0.095),(0.441±0.053) and (0.212±0.117),respectively.IκB-α protein level in the the control group, mild proup and severe group was gradually and significantly reduced(P<0.05). The HDAC3 protein level in placenta of the control group, mild proup and severe group was (0.224±0.061) (0.079±0.021) and (0.072±0.024), respectively. HDAC3 protein level was not significantly lower in severe group than that in mild group(P>0.05).But compared with the control group,both of them were significantly reduced(P<0.05).The acetyl-NF-κB protein level in placenta of the control group, mild proup and severe group was (0.217±0.079),(0.469±0.033) and (0.673±0.091), respectively. Acetyl-NF-κB protein level in the the control group, mild proup and severe group was gradually and significantly increased (P<0.05). (4) The protein levels of NF-κB in placenta was positively correlated with serum levels of TBA,ALT and AST(the correlation coefficient is 0.858, P<0.05; 0.881, P<0.05; 0.879, P<0.05; respectively). The protein levels of IκB-α in placenta was negatively correlated with serum levels of TBA,ALT and AST(the correlation coefficient is-0.888, P<0.05;-0.853, P<0.05;-0.867, P<0.05; respectively). The protein levels of HDAC3 in placenta was negatively correlated with serum levels of TBA,ALT and AST(the correlation coefficient is-0.751, P<0.05;-0.680, P<0.05;-0.729, P<0.05; respectively). The protein levels of acetyl-NF-KB in placenta was positively correlated with serum levels of TBA,ALT and AST(the correlation coefficient is 0.829, P<0.05; 0.887, P<0.05; 0.892, P<0.05; respectively).Conclusions The immune imbalance of ICP placenta,as well as the abnormal expression of HDAC3-NF-κB signailing pathway,miaht take part in the process of ICP.