糖尿病大鼠血管内皮生长因子产生的升高及其对移植胰岛血管再生和功能的影响。
Elevation of vascular endothelial growth factor production and its effect on revascularization and function of graft islets in diabetic rats.
作者信息
Cheng Ying, Liu Yong-Feng, Zhang Jia-Lin, Li Tie-Min, Zhao Ning
机构信息
Organ Transplant Unit of First Affiliated Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, Liaoning Province, China.
出版信息
World J Gastroenterol. 2007 May 28;13(20):2862-6. doi: 10.3748/wjg.v13.i20.2862.
AIM
To determine whether the elevated vascular endothelial growth factor (VEGF) expression produced by the transfected vascular endothelial cells (VECs) could stimulate angiogenesis of the graft islets and exert its effect on the graft function.
METHODS
Thirty diabetic recipient rats were divided into three groups (n=10 per group). In the control group, 300 IEQ islets were transplanted in each rat under the capsule of the right kidney, which were considered as marginal grafts. In the VEC group, VEC together with the islets were transplanted in each rat. In the VEGF group, VEC transfected by pIRES2-EGFP/VEGF165 plasmid and the islets were transplanted in each rat. Blood glucose and insulin levels were evaluated every other day after operation. Intravenous glucose tolerance test (IVGTT) was performed 10 d after the transplantation. Hematoxylin and eosin (HE) staining was used to evaluate the histological features of the graft islets. Immunohistochemical staining was used to detect insulin-6, VEGF and CD34 (MVD) expression in the graft islets.
RESULTS
Blood glucose and insulin levels in the VEGF group restored to normal 3 d after transplantation. In contrast, diabetic rats receiving the same islets with or without normal VECs displayed moderate hyperglycemia and insulin, without a significant difference between these two groups. IVGTT showed that both the amplitude of blood glucose induction and the kinetics of blood glucose in the VEGF group restored to normal after transplantation. H&E and immunohistochemical staining showed the presence of a large amount of graft islets under the capsule of the kidney, which were positively stained with insulin-6 and VEGF antibodies in the VEGF group. In the cell masses, CD34-stained VECs were observed. The similar masses were also seen in the other two groups, but with a fewer positive cells stained with insulin-6 and CD34 antibodies. No VEGF-positive cells appeared in these groups. Microvessel density (MVD) was significantly higher in the VEGF group compared to the other two groups.
CONCLUSION
Elevated VEGF production by transfected vascular endothelial cells in the site of islet transplantation stimulates angiogenesis of the islet grafts. The accelerated islet revascularization in early stage could improve the outcome of islet transplantation, and enhance the graft survival.
目的
确定转染的血管内皮细胞（VECs）产生的血管内皮生长因子（VEGF）表达升高是否能刺激移植胰岛的血管生成，并对移植功能产生影响。
方法
将30只糖尿病受体大鼠分为三组（每组n = 10）。对照组中，每只大鼠在右肾被膜下移植300个胰岛当量的胰岛，这些被视为边缘移植。在VEC组中，将VEC与胰岛一起移植到每只大鼠体内。在VEGF组中，将用pIRES2-EGFP/VEGF165质粒转染的VEC与胰岛移植到每只大鼠体内。术后每隔一天评估血糖和胰岛素水平。移植后10天进行静脉葡萄糖耐量试验（IVGTT）。苏木精-伊红（HE）染色用于评估移植胰岛的组织学特征。免疫组织化学染色用于检测移植胰岛中胰岛素-6、VEGF和CD34（微血管密度，MVD）的表达。
结果
VEGF组移植后3天血糖和胰岛素水平恢复正常。相比之下，接受相同胰岛且有或无正常VECs的糖尿病大鼠表现为中度高血糖和胰岛素水平，两组之间无显著差异。IVGTT显示，VEGF组移植后血糖诱导幅度和血糖动力学均恢复正常。HE和免疫组织化学染色显示肾被膜下存在大量移植胰岛，VEGF组中这些胰岛被胰岛素-6和VEGF抗体阳性染色。在细胞团中，观察到CD34染色的VECs。其他两组也观察到类似的细胞团，但胰岛素-6和CD34抗体阳性染色的细胞较少。这些组中未出现VEGF阳性细胞。与其他两组相比，VEGF组的微血管密度（MVD）显著更高。
结论
胰岛移植部位转染的血管内皮细胞产生的VEGF升高可刺激胰岛移植的血管生成。早期加速的胰岛血管重建可改善胰岛移植的结果，并提高移植存活率。
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