Research On The Mechanism Of Gastric Mucosa Injury Induced By Macrophage In SAP And Protective Measures

AIM: To investigate the related mechanism of acute gastric mucosal injury and protective effect of clodronate containing liposomes against severe acute pancreatitis(SAP)-triggered acute gastric mucosal injury(AGMI) in rats.METHODS: Clodronate and phosphate-buffered saline(PBS)-containing liposomes were prepared by reverse-phase evaporation. The SAP rat model was established by injecting sodium taurocholate into subcapsular space of pancreas. Sprague-Dawley(SD) rats were randomly divided into three groups: control(C), SAP plus PBS-containing liposome(P) and SAP plus clodronate containing liposome(T). After 2 and 6 hours, serum are obtained, and meanwhile the tissue of pancreas and gasric mucosa were harvested respectively. Serum tumor necrosis factor(TNF-α) levels were estimated by ELISA. Pathological changes in the gastric mucosa and pancreas were observed by hematoxylin and eosin(HE) staining. Apoptotic cells were detected by terminal deoxynucleotidyl transferase d UTP nick end labeling staining. The numbers of macrophages in the gastric mucosa were analyzed by CD68 immunohistochemical staining.RESULTS:(1) The TNF-α levels were significantly higher in the P group than that in the C group(2h,145.13±11.50 vs23.2±2.03;6 h,245.06±12.11 vs30.28±6.07,P<0.05),and they were significantly lower in the T group than that in the P group(2h,93.24±23.11 vs 145.13±11.50;6h,135.18±13.10 vs245.06±12.11,P<0.05).(2) The pathological scores of the pancreas were lower in the T group than in the P group(2h,1.88±0.83 vs4.13±0.83; 6 h,2.87±0.64 vs 6.25±0.88,P<0.01). The pathological scores of the gastric mucosa were also lower in the T group than in the P group(2 h,1.12±0.64 vs2±0.75; 6 h,1.58±0.53 vs 3±1.31,P<0.05).(3) In addition,increased CD68 levels were observed in the gastric mucosa of the P group compared with the C group.(4) Clodronate containing liposomes decreased the CD68 levels in the mucosa of the T group. The apoptotic indexes of the gastric mucosa were higher in the T group than in the P group(2 h,15.7±0.92 vs11.5±1.64; 6 h,21.12±1.06 vs12.6±2.44,P<0.01).CONCLUSION:(1) Gastric macrophages contribute to the pathogenesis of gastric injury in SAP.(2) Clodronate containing liposomes have protective effects against AGMI in rats with SAP, by depleting the macrophages.