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目的探讨NKG2D mAb能否单独作为共刺激信号阻断剂延长自发性非肥胖型糖尿病(NOD)小鼠移植移岛的有功能存活期;NKG2D mAb和CD154 mAb是否有协同作用。方法将分离、纯化的BABL/c小鼠胰岛植入自发糖尿病的NOD小鼠左肾包膜下,移植成功的小鼠分成4组:对照组,NKG2D mAb治疗组,CD154 mAb治疗组和联合治疗组(NKG2D mAb+CD154 mAb)。通过小鼠尾静脉血监测血糖,记录胰岛移植物有功能存活期;胰岛移植物所在肾脏行HE染色和CD3、CD4、CD8免疫组织化学染色。结果 NKG2D mAb治疗组移植物有功能存活期无延长(5~11 d,对照组6~11 d,两者差异无统计学意义),CD154 mAb治疗能明显延长移植物有功能存活期〔20~64 d,中位期41 d,和NKG2D mAb治疗组及对照组比较差异均有统计学意义(P<0.05)〕,联合治疗组较CD154 mAb治疗能延长移植物有功能存活期(23~84 d,中位期51 d,但差异无统计学意义)。各组发生排斥时胰岛移植所在肾脏均见淋巴细胞浸润,CD3、CD4、CD8染色结果无明显差异。结论 CD154 mAb能明显延长NOD小鼠胰岛移植物有功能生存期;单独使用NKG2D mAb治疗,不能延长胰岛移植物有功能生存期;联合治疗有效,但仍不能诱导移植物长期存活。
Objective To investigate whether NKG2D mAb can act as a co-stimulatory signal blocker alone to prolong the functional survival of spontaneous non-obese diabetic (NOD) mice transplanted to the island. Is NKG2D mAb and CD154 mAb synergistic. Methods The isolated and purified islets of BABL / c mice were implanted into the left renal capsule of spontaneously diabetic NOD mice. The mice were divided into 4 groups: control group, NKG2D mAb group, CD154 mAb group and combination therapy Group (NKG2D mAb + CD154 mAb). The blood glucose was monitored by the tail vein blood of mice and the functional survival of islet allografts was recorded. The kidneys of islet grafts were stained with HE and CD3, CD4 and CD8 immunohistochemical staining. Results There was no prolongation of functional survival of NKG2D mAb treated group (5 ~ 11 days, control group 6 ~ 11 days, no significant difference between the two), CD154 mAb treatment can significantly prolong graft functional survival 〔20 ~ Compared with NKG2D mAb treatment group and control group, the difference was statistically significant (P <0.05) at 64 d, median 41 d, and treatment with CD154 mAb could prolong the functional survival of graft (23-84 d, the median 51 d, but the difference was not statistically significant). When rejection occurred in all groups, the kidneys in allograft recipients were infiltrated with lymphocytes. The results of CD3, CD4 and CD8 staining showed no significant difference. Conclusion CD154 mAb can significantly prolong the functional survival of islet grafts in NOD mice. Treatment with NKG2D mAb alone can not prolong the functional survival of islet grafts. Combination therapy is effective, but it still can not induce long-term graft survival.