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通过体内给予编码人白细胞介素-10的质粒DNA对实验性自身免疫性甲状腺炎小鼠进行基因治疗。

Gene therapy of experimental autoimmune thyroiditis mice by in vivo administration of plasmid DNA coding for human interleukin-10.

作者信息

Zhang Zhen-Lin, Lin Bo, Yu Lu-Yang, Shen Shui-Xian, Zhu Li-Hua, Wang Wei-Ping, Guo Li-He

机构信息

Department of Osteoporosis, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China.

出版信息

Acta Pharmacol Sin. 2003 Sep;24(9):885-90.

Abstract

AIM

To investigate the effect of interleukin-10 (IL-10) gene on experimental autoimmune thyroiditis mice.

METHODS

Mice were immunized to induce autoimmune thyroiditis with porcine thyroglobulin (pTg), and thyroids of mice were injected with IL-10 DNA. On d 28 after immunization with pTg, mRNA expression of IL-10 in thyroid glands was detected and thyroid specimens were histopathological studied.

RESULTS

The mRNA expression of IL-10 was detected in thyroid glands on d 7 and 14 after injection of IL-10 plasmid DNA or on COS-7 cells 48 h after IL-10 plasmid DNA transfection. In addition, hIL-10 levels in culture media significantly increased 48 h and 72 h after IL-10 plasmid DNA transfection. Infiltration index of lymphocytes (1.1+/-0.4) in thyroids of IL-10-treated mice was significantly lower than that of pcDNA3-null-treated mice (2.2+/-0.5) (P<0.01). Compared with pcDNA3-null control mice, IL-10-treated mice had lower levels of serum IFN-gamma (P<0.01).

CONCLUSION

The direct injection of DNA expression vectors encoding IL-10 into thyroid significantly inhibited development of lymphocytic infiltration of thyroid of autoimmune thyroiditis mice, and alleviated the progression of this disease.

摘要

目的

研究白细胞介素-10(IL-10)基因对实验性自身免疫性甲状腺炎小鼠的影响。

方法

用猪甲状腺球蛋白(pTg)免疫小鼠以诱导自身免疫性甲状腺炎,然后向小鼠甲状腺注射IL-10 DNA。在pTg免疫后第28天,检测甲状腺中IL-10的mRNA表达,并对甲状腺标本进行组织病理学研究。

结果

在注射IL-10质粒DNA后第7天和第14天,或在IL-10质粒DNA转染48小时后的COS-7细胞中,均可检测到甲状腺中IL-10的mRNA表达。此外,IL-10质粒DNA转染后48小时和72小时,培养基中的hIL-10水平显著升高。IL-10处理组小鼠甲状腺淋巴细胞浸润指数(1.1±0.4)显著低于pcDNA3空载体处理组小鼠(2.2±0.5)(P<0.01)。与pcDNA3空载体对照小鼠相比,IL-10处理组小鼠血清IFN-γ水平较低(P<0.01)。

结论

将编码IL-10的DNA表达载体直接注射到甲状腺中,可显著抑制自身免疫性甲状腺炎小鼠甲状腺淋巴细胞浸润的发展,并减轻该病的进展。

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