Influence Of N-acetylcysteine On Toll Like Receptor And Its Protective Effect On Liver And Lung In Mice After Ischemia-reperfusion Injury

Objective: To investigate the influence of NAC on TLR2/4 gene expression and the protective effect of NAC on liver and lung in mice after hepatic ischemia/reperfusion injury.Methods: BALB/c mice were used in a model of partial hepatic I/R injury and randomly subjected to sham-operated control group (SH), hepatic ischemia/reperfusion group (I/R) or NAC pretreated in hepatic I/R group (I/R-NAC). The level of TNF-αin portal vein and plasma ALT were measured at 1hour and 3hour respectively after reperfusion. Lung tissue wet-to-dry weight ratio compared,samples of lung tissue were sent for histological evaluation. The expression of TLR2/4 mRNA and protein in liver and lung was observed with RT-PCR and Western blot at the same time points.Results: 1. Lung tissue W/D ratio showed significant difference between two groups (P<0.05);histological evaluation showed severe changes in lung tissue in I/R group. 2. The expressions of TLR2/4 mRNA and protein in liver and lung increased obviously after hepatic I/R injury(P<0.01). 3. The level of TNF-αand ALT in portal vein increased continually in I/R group at 1hour and 3hour of reputation compared with SH group(P<0.01). 4. Compared with I/R group, the lung injury lessened in I/R-NAC group; the expressions of TLR2/4 mRNA and protein in liver and lung in I/R-NAC was decreased at the same time point (P<0.05); the level of TNF-αand ALT declined significantly in the group pretreated by NAC (P<0.05).Conclusion: TLR2/4 was activated in liver and lung in the process of partial hepatic I/R injury. N-acetylcysteine can inhibit the activation of TLR2/4 and the induction of TNF-αresulted from I/R injury via modulating the state of oxidoreduction, thus it might mitigates liver and lung injury following partial hepatic ischemia-reperfusion in mice.