Study On The Role Of Inhibitor Of NF-κB In The Regulation Of BSEP And NTCP By Estrogen

Objectives:To explore the acid bile concentration in medium and the exression of NTCP and BSEP mRNA of the liver cells which have been effected with different levels of NF-κB inhibitor PDTC and estrogen. To investigate the relationship between NF-κB and BSEP/NTCP. Use this to analyze the role of NF-κB in the nosogenesis of intrahepatic cholestasis of pregnancy and the relationship of severity and prognosis. To intend to investigate the clinical application value of NF-κB in the patients of intrahepatic cholestasis of pregnancy.Methods:Biochemical method and reverse transcription polymerase chain reaction (RT-PCR) were applied to detect the acid bile concentration in medium and the expression of NTCP and BSEP of gene transcription of liver cells. Use this to analyze the role of NF-κB in the nosogenesis of intrahepatic cholestasis of pregnancy.Results:(1) Liver cells were treated by estrogen for 6h,12h,18h,24h,30h and 36h, RT-PCR showed that the mRNA expressions of BSEP and NTCP in liver cells were significantly lower than those of liver cells untreated by estrogen, P<0.05. But the 6-24h in each group no significant changes in bile acid (P> 0.05),24h and 30h group between bile acid concentration was statistically significant (P<0.05),30h,36h, no significant between (P>0.05). (2) Liver cells were treated by different levels of estrogen for 24h, showed that bile acid and the mRNA expressions of BSEP and NTCP in liver cells treated by physiological concentration of estrogen were not significantly lower than those of liver cells untreated by estrogen, not statistically significant, P>0.05. But high concentration of estrogen group compared with bile acid normal liver cells were decreased, BSEP and NTCP mRNA than the decline was statistically significant (P<0.05), high concentration of estrogen in each group was statistically significant (P<0.05). (3) In PDTC combined estrogen groups, bile acid concentration, BSEP and NTCP expression was significantly higher than estrogen alone increased significantly (P<0.05), PDTC combined estrogen group results among the groups was statistically significant (P<0.05).Conclusions:(1) Physiological concentrations of estrogen does not cause decreased expression of BSEP and NTCP, higher than the physiological concentration of estrogen can cause the expression of BSEP and NTCP decreased in a dose dependent manner. (2) NF-κB may be involved in estrogen regulation of BSEP and NTCP, estrogen may be mediated by NF-κB pathway on the expression of BSEP and NTCP plays a negative regulatory role.