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目的探讨腺病毒介导的鼠IL-10(Ad-rIL-10)基因对非肥胖型糖尿病(NOD)小鼠1型糖尿病早期胰岛β细胞的保护作用。方法随机将46只NOD小鼠分为4组:生理盐水对照组10只、糖尿病对照组12只、空载体对照组12只、Ad-rIL-10组12只。除生理盐水对照组外,其他组腹腔注射环磷酰胺诱导糖尿病早期模型。成模后,Ad-rIL-10组立即给予腹腔注射含Ad-rIL-10的重组腺病毒液0.1 mL、空载体对照组给予含Ad-eGFP的重组腺病毒液0.1 mL,其他组给予等量生理盐水。每周检测小鼠体质量、血糖。3周后处死小鼠,留取小鼠血清标本,采用ELISA法测定血清C肽、IFN-γ、IL-4及IL-10水平;制作胰腺标本,免疫组化法观察小鼠胰腺炎症浸润程度和rIL-10局部表达情况。结果与生理盐水对照组相比,成模后其他组血糖水平、体质量变化有明显差异(P均<0.05),血清IFN-γ水平明显增高(P均<0.05),而IL-4、IL-10和C肽水平明显降低(P均<0.05)。糖尿病对照组、Ad-rIL-10组、空载体对照组血糖水平、体质量、胰岛炎症浸润程度及血清学指标变化不明显。结论 Ad-rIL-10基因对NOD小鼠1型糖尿病早期胰岛炎症无明显减轻作用,对残余胰岛β细胞无明显保护作用。
Objective To investigate the protective effect of adenovirus-mediated murine IL-10 (Ad-rIL-10) gene on early pancreatic β-cells in non-obese diabetic (NOD) mice. Methods Forty-six NOD mice were randomly divided into four groups: saline control group (n = 10), diabetes control group (n = 12), empty vector control group (n = 12) and Ad-rIL-10 group (n = 12). In addition to the saline control group, the other groups were injected intraperitoneally with cyclophosphamide-induced diabetic model. After injection, 0.1 mL of recombinant adenovirus containing Ad-rIL-10 was injected intraperitoneally into Ad-rIL-10 group, 0.1 mL of recombinant adenovirus containing Ad-eGFP in empty vector control group, Physiological saline. Weekly test the body weight of mice, blood glucose. After 3 weeks, the mice were sacrificed, the serum samples of mice were collected, and the levels of serum C-peptide, IFN-γ, IL-4 and IL-10 were measured by ELISA. Pancreatic tissues were made. Immunohistochemical method was used to observe the degree of pancreatic inflammatory infiltration And rIL-10 local expression. Results Compared with the saline control group, there were significant differences in blood glucose and body weight among other groups (all P <0.05) and serum IFN-γ levels (P <0.05), while IL-4, IL -10 and C peptide levels were significantly lower (P all <0.05). There were no significant changes in blood glucose level, body weight, infiltration of pancreatic islets and serological parameters in diabetic control group, Ad-rIL-10 group and empty vector control group. Conclusion The Ad-rIL-10 gene has no significant effect on the early islet inflammation of NOD mice with type 1 diabetes, and has no significant protective effect on the residual islet β cells.