The role of TLR4 signaling pathway in obstructive jaundice liver injury

Objective To study the roles of TLR4 sigaling pathway in obstructive jaundice liver injury. Methods Sixty SD rats were randomly divided into Obstructive Jaundice + Polymyxin B group(Group OJ+PMB,n=15),Obstructive Jaundice group(Group OJ,n=15),Sham-operated group(Group SO,n=15) and Blank Control Group(Group CG,n=15).The obstructive-jaundice rat model was established by bile duct ligation.Specimens were collected on the 7th,14th and 21st day after operation.Serum endotoxin(LPS),alanine aminotransferase(ALT) and total bilirubin(TBI) were measured;Hepatic pathological changes were examined under the microscope in HE-stain sections,;Expression of TLR4 protein and NF-κB p65 activity were measured with ELISA;TLR4 mRNA expression was determined with RT-PCR. Results Significant elevation of endotoxin,ALT,TBI,TLR4 and NF-κB p65 was observed in both Group OJ+PMB and Group OJ when comparing with those in Group SO and Group CG at all time points(P0.01).Meanwhile,TLR4 was significantly positively correlated with ALT,LPS and NF-κB p65(r=0.875,0.848 and 0.877,respectively;P0.01).Furthermore,hepatic pathological change was also positively correlated with TLR4 expression.Serum indicators were significantly reduced on 21st day in Group OJ+PMB,compared with those in Group OJ(P0.01),with alleviation in pathological injury. Conclusion Expression of TLR4 aggravates obstructive jaundice liver injury through LPS-TLR4-NF-κB pathway.PMB alleviates the liver injury against endotoxin.