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Hemo oxygenase-1 induction in vitro and in vivo can yield pancreas islet xenograft survival and improve islet function
Ist Teil von
Chinese medical journal, 2011-10, Vol.124 (20), p.3378-3385
Ort / Verlag
China: Department of Surgery Shanghai First Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China%Department of Endocrine and Metabolism Shanghai First Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China%Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China%Department of Surgery, Shanghai First Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Erscheinungsjahr
2011
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
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.