基于谷氨酸脱羧酶65的口服疫苗对链脲佐菌素诱导的1型糖尿病小鼠的治疗作用

吴伊玲; 尤琪; 吴洁

doi:10.11665/j.issn.1000-5048.20210515

基于谷氨酸脱羧酶65的口服疫苗对链脲佐菌素诱导的1型糖尿病小鼠的治疗作用

中国药科大学生命科学与技术学院，南京 211198

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出版历程
- 收稿日期: 2021-03-23
- 修回日期: 2021-05-16
- 刊出日期: 2021-10-24

Therapeutic effect of oral vaccine based on glutamate decarboxylase 65 on streptozotocin-induced type 1 diabetic mice

School of Life Science and Technology, China Pharmaceutical University,Nanjing 211198, China

摘要

摘要: 探讨基于谷氨酸脱羧酶65（GAD65）的口服疫苗对链脲佐菌素（STZ）诱导的1型糖尿病（T1D）模型小鼠的治疗作用。采用小剂量多次腹腔注射STZ建立T1D模型。使用溶剂扩散法制备融合蛋白CTB-GADIII与海藻酸钙纳米疫苗（Ca-Alg-GADIII），灌胃T1D小鼠，1周1次，连续5周，每周记录小鼠血糖和体重。通过糖耐量测定（OGTT）和胰腺组织病理分析研究口服疫苗抗T1D药效学。通过ELISA检测血清中谷氨酸脱羧酶抗体（GADA）和胰岛素自身抗体（IAA）、相关细胞因子IL-4、IFN-γ和TGF-β1的含量，流式检测CD4⁺T细胞分型情况，对口服疫苗抗T1D作用的免疫学机制进行初步探讨。结果显示，疫苗免疫后的小鼠空腹血糖有一定的改善，糖耐量提高，胰腺损伤减少，胰岛素分泌增加，GADA及IAA滴度显著下降，肠系膜淋巴结和胰腺淋巴结中CD4⁺ T细胞免疫平衡有一定的改善。实验结果表明Ca-Alg-GADIII口服疫苗对STZ诱导的T1D小鼠具有一定的治疗作用。
- 1型糖尿病 /
- 谷氨酸脱羧酶65 /
- 海藻酸钙 /
- 口服疫苗 /
- 免疫耐受
Abstract: To investigate the therapeutic effect of oral vaccine based on glutamate decarboxylase 65 (GAD65) on streptozotocin (STZ) -induced type 1 diabetic (T1D) mice, the mice model of T1D was established by intraperitoneal injection of low dose multiple STZ. CTB-GADIII encapsulated with calcium alginate (Ca-Alg-GADIII) was formulated using crosslinking technology with sodium alginate and calcium chloride, and was administered intragastric to T1D mice once a week for 5 consecutive weeks.Blood glucose and body weight of the mice were recorded weekly, and pharmacodynamics against T1D of Ca-Alg-GADIII were investigated by glucose tolerance assay (OGTT) and pancreatic histopathological analysis. The levels of glutamic acid decarboxylase antibody (GADA), and insulin autoantibody (IAA) and related cytokines (IL-4, IFN-γ, TGF-β1) in serum were detected by ELISA, and the CD4⁺T cell subsets were detected by flow cytometry. The immunological mechanism of oral vaccine against T1D was preliminarily discussed. The results showed that the disease-related indicators improved in immunized mice: fasting blood glucose improved, glucose tolerance and insulin secretion increased, pancreatic injury decreased, autoantibodies like GADA and IAA titers significantly decreased, and CD4⁺T cell immune balance in mesenteric lymph node (MLN) and pancreatic lymph node (PLN) improved to some extent. The results suggest that oral vaccine Ca-Alg-GADIII has some therapeutic effect on STZ-induced T1D mice.
- type 1 diabetes /
- glutamic acid decarboxylase /
- calcium alginate /
- oral vaccine /
- immune tolerance

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参考文献(19)

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基于谷氨酸脱羧酶65的口服疫苗对链脲佐菌素诱导的1型糖尿病小鼠的治疗作用

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Therapeutic effect of oral vaccine based on glutamate decarboxylase 65 on streptozotocin-induced type 1 diabetic mice

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