| Objective To observe the potential therapeutic effect of tacrolimus against rats severe acute pancreatitis (SAP) and to unravel the underlying mechanisms. Methods Ninety female SD rats were randomly divided into five groups: the control group, the sodium taurocholate group, and the sodium taurocholate groups received 0.5, 1.0 and 1.5 mg/kg tacrolimus (n=18 per group), and the five groups were randomly divided into 3 h, 6 h, and 12 h time group. The SAP model was developed in rats by retrograde injection of 5 % sodium taurocholate into biliopancreatic duct through duodenal wall. Histopathological changes of lung and pancreas were observed. Expression of tumor necrosis factor-alpha (TNF-α) and MMP-9 in serum, myeloperoxidase (MPO) activity of pancreatic tissue, and the protein content of bronchoalveolar lavage fluids (BALF) were detected. Another 36 female SD rats were randomly divided into three groups: the control group, the sodium taurocholate group, and the sodium taurocholate groups received 1.0 mg/kg tacrolimus (n=12 per group), the 3 h, 6 h, and 12 h survival rates of each group were evaluated. Results Histopathological stain revealed the gradually aggravated injuries of lung and pancreas in SAP rats which were relieved after being exposed to tacrolimus. The expression of TNF-αand MMP-9, the MPO activity of pancreas tissue, and the protein content of BALF were significantly increased in SAP rats (P<0.01). However, the increases were significantly down-regulated (P<0.01) while the survival rates was raised (P<0.01) after treatment with tacrolimus at a non-dose-dependent fashion. Conclusions Tacrolimus could effectively relieve the acute pancreatitis severity and the associated lung injury. The mechanisms may be related to the reduction of lung blood capillarypermeability, the down-regulated inflammatory reaction mediated by TNF-α, MMP-9 and other inflammatory factors, and the decreased MPO activity of pancreas. |
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