胰岛素和CTLA4Ig共表达基因治疗小鼠糖尿病模型的效果

发布时间：2018-02-24 13:29

本文关键词： 型糖尿病 CTLAIg 基因治疗腺病毒　出处：《现代免疫学》2017年02期 　论文类型：期刊论文

【摘要】：为观察导入CTLA4Ig基因能否延长胰岛素基因治疗的疗效时间,静脉注射链脲佐菌素(streptozotocin,STZ)制备1型糖尿病(type 1diabetes mellitus,T1DM)小鼠模型,将24只造模成功的雄性C57小鼠随机分为注射空载腺病毒组、表达胰岛素的腺病毒组(recombinant adenovirus vector/insulin,rAdV/Ins)和共表达胰岛素和CTLA4Ig基因的重组腺病毒(recombinant adenovirus vector/insulin-CTLA4Ig,rAdV/Ins-CTLA4Ig)组,每组8只。采用实时定量聚合酶链反应(quantitative real-time polymerase chain reaction,qRT-PCR)方法检测胰岛素、CTLA4Ig及其相关基因在小鼠肝组织的mRNA表达水平。应用简便血糖仪定期检测小鼠血糖水平。rAdV/Ins-CTLA4Ig组小鼠肝组织中CTLA4Ig mRNA的表达量显著高于rAdV/Ins组和空载腺病毒组(P0.01)。rAdV/Ins-CTLA4Ig组小鼠肝组织中IFN-γmRNA的表达显著低于空载腺病毒组(P=0.04)。与注射空载腺病毒组相比较,rAdV/Ins-CTLA4Ig和rAdV/Ins两组小鼠的血糖水平显著降低(均P0.05),且rAdV/Ins-CTLA4Ig组小鼠较rAdV/Ins组小鼠能维持更长的正常血糖时间(P0.01)。胰岛素和CTLA4Ig共表达基因的重组腺病毒能转染小鼠肝脏,CTLA4Ig能在肝内成功表达并通过抑制炎症反应延长了胰岛素基因表达时间。
[Abstract]:Effect of time to observe CTLA4Ig gene can prolong the insulin gene therapy, intravenous injection of streptozotocin (streptozotocin, STZ) preparation of type 1 diabetes mellitus (type 1diabetes, mellitus, T1DM) mouse model, 24 successful model of male C57 mice were randomly divided into empty adenovirus injection group, the expression of adenovirus the insulin group (recombinant adenovirus vector/insulin, rAdV/Ins) and a recombinant adenovirus co expressing insulin and CTLA4Ig gene (recombinant adenovirus vector/insulin-CTLA4Ig, rAdV/Ins-CTLA4Ig) group, 8 rats in each group. Using real-time quantitative polymerase chain reaction (quantitative real-time polymerase chain reaction, qRT-PCR) method for the detection of insulin, the expression level of mRNA CTLA4Ig and its related genes in liver tissue application of a simple CTLA4Ig mice. Blood glucose meter regular blood glucose level of.RAdV/Ins-CTLA4Ig mice were detected in liver tissue of mice The expression of mRNA was significantly higher than that of rAdV/Ins group and empty adenovirus group (P0.01) expression in liver tissue of.RAdV/Ins-CTLA4Ig IFN- gamma mRNA was significantly lower than that of empty adenovirus group (P=0.04). Compared with empty adenovirus injection group, the blood glucose level of rAdV/Ins-CTLA4Ig and rAdV/Ins of the two groups were significantly decreased (P0.05), normal blood glucose and rAdV/Ins-CTLA4Ig mice compared with rAdV/Ins mice can maintain a longer (P0.01). The recombinant adenovirus can transfect mouse liver co expression of insulin and CTLA4Ig, CTLA4Ig can be successfully expressed in the liver by inhibiting the inflammatory reaction and prolong the time of insulin gene expression.

【作者单位】：复旦大学附属金山医院内分泌科;
【基金】：上海市卫计委科研基金(2012-225) 国家自然科学基金(81471004)
【分类号】：R587.1;R-332

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