The therapeutic effect of tacrolimus against the lung injuries induced by severe acute pancreatitis in rats

Objective To observe the potential therapeutic effect of tacrolimus against lung injuries induced by severe acute pancreatitis(SAP) in rats and investigate its mechanism.Methods Fifty-four female SD rats were randomly divided into 3 groups: Control group(group C), SAP group(group S) and SAP+ tacrolimus treatment group(group ST) (n=18 each group). Serum levels of tumor necrosis factor-alpha(TNF-α) and matrix metalloproteinase-9(MMP-9), myeloperoxidase(MPO) activity of lung tissue and the protein content of bronchoalveolar lavage fluids(BALF) were evaluated 3,6, and 12h after operation. The survival rates of 3 groups were also evaluated, and histopathologic changes of lung and pancreas were observed.Results In group S, serum level of TNF-α and MMP-9, MPO activity of lung tissue, and the protein content of BALF were significantly increased than those in group C (all P0.01). All the indicators of group ST were significantly decreased 12h after operation as compared with group S [TNF-α:(171.31±19.58)vs(243.17±26.19);MMP-9:(1 658.32±27.49)vs(2 987.34±34.53);MPO:(2.75±0.22)vs(11.27±0.49); BALF:(631.58±57.25)vs(1 987.39±158.34)] (P0.01). Histopathology showed that the lung and pancreas injuries in group S were gradually aggravated with disease progression, and alleviated obviously with tacrolimus treatment.Conclusions Tacrolimus can relieve the severity of lung injuries of pancreatitis rats, increase survival rate, and provide a certain therapeutic effect for SAP rats. The mechanism of tacrolimus effect may be related to the reduction of lung blood capillary permeability, and the inhibition of serum level of TNF-α and MMP-9, lung MPO, and other inflammatory factors.