摘要
Background The induced expression of heme oxygenase-1 （HO-1） in donor islets improves allograft survival. Cobalt protoporphyrin （CoPP） could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction. Methods Islet xenografts treated with CoPP-induction and CoPP＋ Zinc protoporphyrin （ZnPP） in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon ~ （IFN-y）, tumor necrosis factor a （TNF-a）, interleukin 10 （IL-10） and IL-113 level in serum and their mRNA and HO-1 mRNA and protein expression were examined. Results Islets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 （mRNA： 3.33- and 76.09- fold in vitro and in vivo; protein： 2.85- and 58.72-fold）. The normoglycemia time in induction groups （（14.63±1.19） and （16.88±1.64） days） was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher. Conclusions The HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10.
Background The induced expression of heme oxygenase-1 （HO-1） in donor islets improves allograft survival. Cobalt protoporphyrin （CoPP） could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction. Methods Islet xenografts treated with CoPP-induction and CoPP＋ Zinc protoporphyrin （ZnPP） in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon ~ （IFN-y）, tumor necrosis factor a （TNF-a）, interleukin 10 （IL-10） and IL-113 level in serum and their mRNA and HO-1 mRNA and protein expression were examined. Results Islets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 （mRNA： 3.33- and 76.09- fold in vitro and in vivo; protein： 2.85- and 58.72-fold）. The normoglycemia time in induction groups （（14.63±1.19） and （16.88±1.64） days） was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher. Conclusions The HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10.
