The protection of xenotransplanted murine pancreatic islets by induced expression of heme oxygenase-1 / 中华普通外科杂志

ABSTRACT

Objectlve To explore the mechanism of the protection in high expression of HO-1 induced by CoPP on murine islet xenografts. Method An islet transplantation of a SD rat-to-C57 BL/6 mouse model was established.Mice were randomized into five groups i.e.control,CoPP-induction in vivo,CoPP+ZnPP in vivo.CoPP-induction in vitro and CoPP+ZnPP in vitro and the islet xenografts were transplanted into the subrenal capsule.Normoglycemia time was recorded and insulin-releasing test was performed.IL-10、TNF-α、IL-1β and INF-γ in serum and their cytokine mRNA and HO-1 in xenografts were measured by RT-PCR and Western-blotting.The pathological examination was done to observe the lymphocyte infiltration. Results There Was significant difference in the normoglycemia time between CoPP-induction in vivo and in vitro and other three groups.The results of insulin-releasing stimulated by low level glucose were identical among groups,but that of insulin-releasing stimulated by high-glucose in in vivo group were the hiishest as in CoPP-induction in vivo and in vitro and control group were 187.68 ±19.93、137.22±11.73,91.25±12.64 μIU·ml~(-1)·10islets~(-1)·45 min~(-1),(P<0.05).The IL-10 in serum in CoPP-induction in vivo and in vitro(in vivo72.97±9.74 pg/ml;in vitro70.84±3.56 pg/ml)was significantly hisher than other three groups(control30.57±3.93 pg/ml;CoPP+ZnPP in vivo39.78±3.00 pg/ml;CoPP+ZnPP in vitro35.42±4.30 pg/ml).The expression tendency of IL-10 mRNA was similar to that of insulin secretion.There was no significant difieFence in TNF-α、IL-1β and INF-γ.The expression of HO-1 by PCR and Western-blot analysis in CoPP-induction in vivo and vitro was higher than other three groups.The pathological examination showed that fewer lymphocytes infiltrated into the islet xenografts from CoPP-treated in comparison with xenografts from other three groups. Conclusion HO-1 could improve the survival of islet xenograftthe induetion of HO-1 expression in vivo was much mole efficient than in vitro.The CoPP-induction could be related to immune modulation of IL-10.