Effects of zinc protoporphyrin on the colonic interstitial cells of Cajal and dysfunction in diabetic rats

Abstract

Objective To assess the effects of zinc protoporphyrin (ZnPP), an inhibitor of the heme oxygenase (HO), on the colonic interstitial cells of Cajal (ICC) of diabetic rats with colonic slow transit. Methods Diabetes mellitus (DM) model was induced by intraperitoneal injection of streptozotocin (STZ) in Sprague-Dawley rats. Twenty four successfully established DM rats were selected, and 16 healthy rats were served as controls. Six weeks later, gastrointestional (GI) dysfunction was observed by charcoal propulsion experiment in 8 DM rats and 8 controls. The rest rats in DM group were divided into 2 groups: DM rats intraperitoneal injected with PBS (n=8) or with 10 μmol/kg of ZnPP (n = 8) every other day for 3 weeks. The rats in control group (n = 8) were intraperitoneally injected with PBS. The levels of HO and c-kit (the special receptor of ICC) expression were detected by Western blotting. The distribution of ICC was observed by immunohistochemistry and the area of c-kit positive cells was counted. Results The GI propulsion rate in DM rats interfered with PBS was significantly declined compared to that in the controls (63.0%± 1.2% vs 71.8%±2.0%, P 0.05). The expression of HO-1 in close and distant colon of DM rats interfered with ZnPP was decreased (P< 0.05). The expression of HO-2 in close colon and the area of c-kit positive cells of DM rats interfered with PBS was reduced compared with that in controls (P<0.05), but both were improved in DM rats interfered with ZnPP (P<0. 05). Conclusion Administration of ZnPP might be able to protect ICC by its blockage of HO-1 in DM rats with gastrointestinal dysfunction. Key words: Diabetes mellitus; Zinc protoporphyrin; Gastrointestinal motility; Rat