TLR4 Overexpression After Orthotopic Liver Autotransplantation Contributes To Acute Lung Injury In Rats

Abstract

Acute lung injury(ALI) is a common and severe complication of orthotopic liver transplantation(OLT), while the underlying mechanism of post‐OLT ALI is not very clear. Toll‐like receptor (TLR) 4 is an important TLR family member that plays a key role in the innate immune system. TLR4 is increased after OLT, accompanied with increased inflammatory response and ALI (Chin Med J, 2009,122:895–899). We hypothesized that TLR4‐mediated inflammation response may play a ctitical role in ALI during OLT. Healthy SD rats (n=8/group) were randomly divided into sham operated control group (C) and OLT groups with different durations (4, 8 and 16 hours) of reperfusion in the presence or absence of TLR4 siRNA interference performed 48 hours before OLT. Lung tissue TLR4 gene and protein expressions were significantly increased 8 hours after OLT and onwards, which was coincident with increased tissue levels of tumor necrosis factor (TNF) α, interleukin (IL)6 and IL‐1β, and evident lung pathological damage manifested as increased lung injury scores and increased lung water content and functional impairment manifested as reduced PaO2 (all P<0.05 vs. OLT vs. C). TLR4 dominant negative siRNA prevented all the above changes after OLT. It is concluded that TLR4 overexpression, potentially by stimulting proinflammatory cytokine over production, plays a critical role in the developent of ALI after OLT.The study was supported by National Natural Science Foundation of China grant (No. 30801080 and 30972858).