Abstract: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 P<0.01). 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）］ (P<0.01). 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.