异种血管内皮细胞疫苗治疗Lewis大鼠子宫内膜异位症的动物模型

目的： 探索一种以抑制异位病灶新生血管为靶点的治疗子宫内膜异位症（内异症）的新方法。方法 ：将处于对数生长期的人脐静脉内皮细胞固定后溶于PBS中，作为疫苗，并培养人成纤维细胞、大鼠主动脉内皮细胞作为对照细胞。手术移植法建立Lewis大鼠内异症（EMT）的动物模型，然后随机将EMT模型分为6组，分别注入不同浓度的疫苗和对照组细胞。A组（治疗组）注射人脐静脉内皮细胞（1×105），B组（治疗组）注射人脐静脉内皮细胞（5×105），C组（治疗组）注射人脐静脉内皮细胞（1×106），D组(对照组)注射PBS 0.5 ml，E组(对照组)：注射人成纤维细胞（5×105），F组(对照组)注射大鼠主动脉内皮细胞（5×105），四周后观察异位病灶微血管密度（MVD）、间质细胞增殖指数、病灶面积的变化；同时用四甲基偶氮唑蓝（MTT）法检测人脐静脉内皮细胞、人成纤维细胞和大鼠主动脉内皮细胞诱导的免疫血清在体外对鼠内皮细胞增殖的影响。结果 ：治疗组（B，C组）异位病灶的面积较治疗前显著缩小（P﹤0.05），与其它组比较，治疗组（B，C组）MVD在治疗后降低(P﹤0.05)，但间质细胞的增殖指数差异无显著性（P>0.05）。人脐静脉内皮细胞诱导的免疫血清在体外能抑制内皮细胞的增殖(P<0.05)。结论：异种血管内皮细胞（人脐静脉内皮细胞）作为疫苗能抑制异位病灶血管形成而使异位病灶面积减小，有望能作为一种内异位症治疗的新方法。

Animal model of endometriosis treated with xenogeneic endothelial cells as vaccines in Lewis rats

OBJECTIVE: To investigate a new therapy for endometriosis, which can inhibit the angiogenesis of ectopic endometrium. METHODS: Xeogeneic endothelial cells (human umbilical vein endothelial cells, HUVECs) were used as vaccines, and a variety of controlled cells (including rat aortic endothelial cells and human fibroblast cells) were cultured, fixed and resuspended in PBS. Thirty-six Lewis rats with experimentally induced endometriosis were divided into 6 groups. Group A was treated with HUVECs (1 x 10(5)); Group B was treated with HUVECs (5 x 10(5)); Group C was treated with HUVECs (1 x 10(6)); Group D (a control group) was treated with PBS (0.5 ml); Group E (a control group) was treated with human fibroblast cells (5 x 10(5)); and Group F (a control group) was treated with rat aortic endothelial cells (5 x 10(5)). Microvessel desity (MVD), area and the proliferative index were deteced in different groups 4 weeks after the treatment. The effect of immune serum on rat endothelial cell proliferation in vivo was determined with methyl thiazolyl tetrazolium (MTT) method. RESULTS: The area of the established endometriotic implant became smaller in Group B and Group C; compared with other groups, MVD decreased after the treatment with HUVECs as vaccines in Group B and Group C (P < 0.05). The proliferative index had no difference among these groups (P > 0.05). The immune sera induced by HUVECs could inhibit the proliferation of endothelial cells of rats in vivo (P < 0.05). CONCLUSION: As vaccines, HU- VECs can inhibit the angiogenesis of ectopic endometrium, and provide a new therapy for endometriosis.