腺相关病毒介导的pdx-1基因表达促进糖尿病大鼠肝脏细胞向胰岛素产生细胞转化的研究(英文)  

Adeno-associated virus-mediated pancreatic and duodenal homeobox gene 1 delivery induced insulin-producing cells in livers of diabetic rats

作　　者：李华[1] 李欣燕[2] 许瑞安[3] 

机构地区：[1]大连医科大学药学院药理教研室 [2]上海交通大学药学院,上海200030 [3]福建华侨大学分子药物学研究所

出　　处：《中国临床药理学与治疗学》2007年第6期614-619,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:胰十二指肠同源盒基因-1(pancreatic duodenal homeobox-1,pdx-1)是胰岛发育和分化过程中重要的转录因子。本实验旨在研究腺相关病毒(adeno-associated virus,AAV)介导的pdx-1基因的表达是否可以诱导糖尿病大鼠肝脏细胞分化成产生胰岛素的细胞,以进一步为糖尿病的细胞替代疗法提供信息。方法:门静脉途径注射AAV-pdx-1或AAV对照载体到大鼠体内。6周后,用RT-PCR和免疫细胞化学法检测肝脏中胰岛素的基因表达及测定大鼠血糖、体重的变化。结果:AAV-pdx-1治疗组明显提高了糖尿病大鼠肝脏中胰岛素的基因表达和胰岛素阳性细胞数,改善了糖尿病大鼠的高血糖状态及增加了体重。结论:AAV-pdx-1可诱导糖尿病大鼠肝脏细胞分化成产生胰岛素的细胞,缓解了糖尿病状态。其分化的机制及分化的肝脏细胞亚群需进一步实验研究,以提高分化效率。Pancreatic and duodenal homeobox gene l（pdx-1） is a crucial transcription factor in pancreatic islet development and differentiation. This study was conducted to evaluate whether pdx-1 delivered by adenoassociated virus （AAV） could induce liver cells to differentiate into insulin-producing cells in diabetic rots and thus provide more information for cell replacement therapy for diabetes. METHODS： Recombinant AAV vector was employed to deliver pdx-lto STZ-indueed diabetic rats via portal vein （4 × 10^11 ）. Blood glucose and body weight were monitored. Gene expression of pdx-1 and insulin were determined by RT-PCR and immunocytotochemistry （ICC） at the 6th week after the injection. RESULTS： AAV-pdx-1 group showed obvious gene expression of pdx-1 and insulin by RT-PCR analysis and the presence of more insulin-positive cells by ICC. Hyperglycemia was partially ameliorated and body weight was also increased in AAV-pdx-1 treated diabetic rats, though still signifi- cantly different from those in the non-diabetic group. CONCLUSION： The data indicate that AAV-pdx-1 can induce more rat liver cells into insulin-producing cells in vivo, thereby ameliorate hyperglycemia. Further experiments are needed to explore which subpopulation of liver cells responds to this development shift and the mechanism of this development shift induced by pdx-1 in order to improve the differentiation efficiency.

关 键 词：腺相关病毒 胰十二指肠同源盒基因-1 胰岛素 糖尿病 高血糖 

分 类 号：R966[医药卫生—药理学]