Hemo oxygenase-1 induction in vitro and in vivo can yield pancreas islet xenograft survival and improve islet function / 中华医学杂志(英文版)
Xi CHEN; Chang SU; Zheng-Yun ZHANG; Ming-Jun ZHANG; Wei-Qiong GU; Xiao-Ying LI; Hong-Wei LI; Guang-Wen ZHOU.
Chinese Medical Journal
; (24): 3378-3385, 2011.
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| WPRIM | ID: wpr-319113
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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 γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10) and IL-1β level in serum and their mRNA and HO-1 mRNA and protein expression were examined.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
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