Direct transfer of A20 gene into pancreas protected mice from streptozotocin-induced diabetes  

作　　者：Lu-yangYU BoLIN Zhen-linZHANG Li-heGUO 

机构地区：[1]InstituteofBiochemistryandCellBiology,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyofSciences,Shanghai200031 [2]CenterforPreventingandTreatingOsteoporosis,OsteoporosisResearchUnit,ShanghaiJiaoTongUniversityAffiliatedSixthPeople＇sHospital,Shanghai200233,China

出　　处：《Acta Pharmacologica Sinica》2004年第6期721-726,共6页中国药理学报（英文版）

基　　金：Project supported by the State Key Basic R&D Programme"973" (NoG1999053905).

摘　　要：AIM: To investigate the efficiency of transfer of A20 gene into pancreas against STZ-induced diabetes. METHODS: PVP-plasmid mixture was directly transferred into the pancreatic parenchyma 2 d before STZ injection. The uptake of plasmid pcDNA3-LacZ or pcDNA3-A20 was detected by PCR and the expression of LacZ was confirmed by histological analysis with X-gal. A20 expression in the pancreas of pcDNA3-A20 transgenic mice was measured by RT-PCR and Western blots. Urine amylase, NO generation, and histological examination were examined. RESULTS: Injection of PVP-plasmid mixture directly into the pancreatic parenchyma increased urine amylase concentration 16 h after operation and reversed it to nearly normal 36 h later. On d 33 LacZ expression could be found in spleen, duodenum, and islets. The development of diabetes was prevented by direct A20 gene transferring into the pancreas and A20-mediated protection was correlated with suppression of NO production. The insulitis was ameliorated in A20-treated mice. CONCLUSION: Injection of PVP-plasmid mixture directly into the pancreatic parenchyma led to target gene expression in islets. Direct transfer of A20 gene into the pancreas protected mice from STZ-induced diabetes.AIM: To investigate the efficiency of transfer of A20 gene into pancreas against STZ-induced diabetes. METHODS: PVP-plasmid mixture was directly transferred into the pancreatic parenchyma 2 d before STZ injection. The uptake of plasmid pcDNA3-LacZ or pcDNA3-A20 was detected by PCR and the expression of LacZ was confirmed by histological analysis with X-gal. A20 expression in the pancreas of pcDNA3-A20 transgenic mice was measured by RT-PCR and Western blots. Urine amylase, NO generation, and histological examination were examined. RESULTS: Injection of PVP-plasmid mixture directly into the pancreatic parenchyma increased urine amylase concentration 16 h after operation and reversed it to nearly normal 36 h later. On d 33 LacZ expression could be found in spleen, duodenum, and islets. The development of diabetes was prevented by direct A20 gene transferring into the pancreas and A20-mediated protection was correlated with suppression of NO production. The insulitis was ameliorated in A20-treated mice. CONCLUSION: Injection of PVP-plasmid mixture directly into the pancreatic parenchyma led to target gene expression in islets. Direct transfer of A20 gene into the pancreas protected mice from STZ-induced diabetes.

关 键 词：ADENOVIRIDAE STREPTOZOCIN insulin-dependent diabetes mellitus gene therapy nitric oxide glucose AMYLASES reversed transcriptase polymerase chain reaction Western blotting 

分 类 号：R576[医药卫生—消化系统] R587.1[医药卫生—内科学]