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重组HSP65-6P277乳酸乳球菌疫苗对链脲佐菌素诱导的1型糖尿病小鼠的降糖作用 被引量：2

Hypoglycemic effect of Lactococcus lactis vaccine containing HSP65-6P277 on streptozotocin-induced type 1 diabetic mice
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摘要 探讨表达HSP65-6P277蛋白的乳酸乳球菌活载体疫苗对链脲佐菌素(STZ)诱导的1型糖尿病小鼠的降糖作用及可能的作用机制。采用多次小剂量腹腔注射STZ建立1型糖尿病模型。将诱导型表达菌株Lactococcus lactis NZ9000pCYT∶HSP65-6P277和组成型表达菌株L.lactis NZ9000 pHJ∶HSP65-6P277及无关蛋白对照菌株L.lactis NZ9000 pCYT∶Nuc灌胃1型糖尿病小鼠(2×109CFU,200μL),每天灌胃1次,连续7 d,之后每周灌胃1次,持续16周。每月从小鼠眼眶静脉丛取血1次,血糖检测仪检测STZ造模小鼠血糖水平并称体重。4个月后将小鼠处死,取小鼠脾脏做脾细胞增殖实验,采用ELISA试剂盒分别检测脾细胞上清液中的IL-10和IFN-γ细胞因子水平以及血清IgG抗体水平。结果显示,与对照组相比,pCYT∶HSP65-6P277组和pHJ∶HSP65-6P277组可以一定程度上降低STZ造模小鼠血糖水平(P<0.05),并能维持其正常体重稳定,降低脾细胞针对HSP65和P277的增殖(P<0.05),脾细胞上清液中IFN-γ细胞因子水平明显降低(P<0.05),血清IgG抗体水平无明显差异(P>0.05)。 To study the hypoglycemic effect and mechanisms of vaccine HSP65-6P277 protein on type 1 diabetic mice induced by streptozotocin（STZ）, Lactococcus lactis live vector was used to express the vaccine protein. The mouse model of type 1 diabetes mellitus were established by intraperitoneal injections of multiple low dose STZ（MLD-STZ）and divided into three groups. The inducible expression strain L. lactis NZ9000 pCYT ∶HSP65-6P277, constitutive expression strain L. lactis NZ9000 pHJ ∶HSP65-6P277 and control strains L. lactis NZ9000 pCYT ∶Nuc were respectively immunized to diabetic mice orally once daily（2×109 CFU, 200 μL）in the first week and once every week in the following weeks lasting for 16 weeks. Fasting blood glucose levels were measured once a month on blood samples taken from orbital venous plexus. Four months later, the mice were sacrificed. Spleen cell proliferation experiment was performed. IL-10 and IFN-γ cytokine levels of spleen cells and serum IgG levels were assayed using ELISA kits. The results showed that pCYT ∶HSP65-6P277 group and pHJ ∶HSP65-6P277 group have low blood glucose（P 〈 0. 05）, and maintain normal body weight, compared with control group（pCYT ∶Nuc）. On the other hand, cytokine IFN-γ levels were significantly lower（P 〈 0. 05）in spleen cells supernatant and spleen cell proliferation was reduced against HSP65 and P277（P〈 0. 05）, but serum IgG levels were not significantly different（P〉 0. 05）.
作者 吴洁 刘晓锐 杨雪 侯景 徐茂磊 申丽丽 黄东成 刘坤锋
机构地区 中国药科大学生命科学与技术学院微基因药学实验室
出处 《中国药科大学学报》 CAS CSCD 北大核心 2014年第1期106-110,共5页 Journal of China Pharmaceutical University
基金 国家自然科学基金资助项目(No.81172973,31270985) 中央高校基本科研业务费研究生专项资助项目(No.JKY2011076) 江苏高校优势学科建设工程资助项目~~
关键词 乳酸乳球菌 疫苗 P277 黏膜免疫 1型糖尿病 Lactococcus lactis vaccine P277 mucosal immune type 1 diabetic mellitus
分类号 Q78 [生物学—分子生物学] R965 [医药卫生—药理学]
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共引文献5

同被引文献56

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中国药科大学学报
2014年 第1期

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