Su Chang, Chen Xi, Zhang Zheng-yun, Gu Wei-qiong, Zhang Ming-jun, Zhou Guang-wen, Li Xiao-ying, Ning Guang, Li Hong-wei
Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Zhonghua Wai Ke Za Zhi. 2009 Aug 15;47(16):1249-52.
To study the protective effect of islet xenograft and its possible mechanism of high expression of heme oxygenase-1 (HO-1) in donor pancreas islet induced by cobalt protoporphyrin (CoPP).
Male SD rats and C57BL/6 mouse were used as donors and recipients respectively. Donors were divided into 3 groups according to different pretreatment 24 hours before donation: control group (injected intraperitoneally with NaCl), induce group [injected intraperitoneally with cobalt-protoporphyrin (CoPP)], block group (injected intraperitoneally with CoPP and zinc protoporphyrin simultaneously). A modified approach was used for islet isolation.Recipients were rendered diabetic by intraperitoneal injection of streptozotocin. Islets were transplanted into mouse subrenal capsule. Postoperative mouse glycemia were monitored daily and normoglycemia time was compared among each group. The receptor mouse serum IL-10 was detected by ELISA approach, and real-time PCR was used to check the expression of IL-10 mRNA in islet graft tissues. The graft tissues were observed for the lymphocyte infiltration after HE staining.
Diabetes mice accepted islets untreated, induced or blocked maintained the euglycemia for (9.3 +/- 1.4), (16.3 +/- 1.5) and (9.7 +/- 1.0) d respectively. The xeno-islets presented HO-1 over-expression survived much longer than that absent (P < 0.05), it was no significance between control group and block group (P > 0.05). The mouse islet serum IL-10 content after induction was (73.0 +/- 9.7) pg/ml, significantly higher than (30.6 +/- 3.9) pg/ml of the untreated group and (32.1 +/- 5.9) pg/ml of the blocked group (P < 0.05), there was no difference between control group and block group (P > 0.05). Moreover, the IL-10 mRNA expression up-regulated statistic significantly in HO-1 induced islet xeno-graft. Pathological examination showed that the graft lymphocyte infiltration of the induced group was obviously less serious than the other two groups.
The higher expression of HO-1 induced by CoPP in vivo would significantly prolong graft survival time and its mechanism could be related to immune modulation of IL-10.
研究胰岛异种移植的保护作用及其可能机制，即钴原卟啉（CoPP）诱导供体胰腺胰岛中血红素加氧酶-1（HO-1）高表达的机制。
分别以雄性SD大鼠和C57BL/6小鼠作为供体和受体。供体根据捐献前24小时的不同预处理分为3组：对照组（腹腔注射NaCl）、诱导组[腹腔注射钴原卟啉（CoPP）]、阻断组（同时腹腔注射CoPP和锌原卟啉）。采用改良方法分离胰岛。受体通过腹腔注射链脲佐菌素诱导成糖尿病模型。将胰岛移植到小鼠肾被膜下。术后每天监测小鼠血糖，并比较各组的血糖正常时间。采用ELISA法检测受体小鼠血清IL-10，实时PCR检测胰岛移植组织中IL-10 mRNA的表达。HE染色观察移植组织中的淋巴细胞浸润情况。
接受未处理、诱导或阻断处理胰岛的糖尿病小鼠血糖正常时间分别为（9.3±1.4）、（16.3±1.5）和（9.7±1.0）天。HO-1过表达的异种胰岛存活时间明显长于未过表达的（P<0.05），对照组和阻断组之间无显著差异（P>0.05）。诱导后小鼠胰岛血清IL-10含量为（73.0±9.7）pg/ml，明显高于未处理组的（30.6±3.9）pg/ml和阻断组的（32.1±5.9）pg/ml（P<0.05），对照组和阻断组之间无差异（P>0.05）。此外，HO-1诱导胰岛异种移植中IL-10 mRNA表达上调有统计学意义。病理检查显示诱导组移植淋巴细胞浸润明显轻于其他两组。
体内CoPP诱导的HO-1高表达可显著延长移植存活时间，其机制可能与IL-10的免疫调节有关。
