中文摘要：

目的探讨多巴胺D5受体是否会通过抑制氧化应激来影响扩张型心肌病（dilated cardiomyopathy）的发生发展。方法建立心脏特异表达人多巴胺D5受体突变基因F173L（α-MHC-h D5F173L）和正常基因（α-MHC-h D5WT）转基因小鼠。用3月龄小鼠,首先检测比较转基因小鼠心脏内ROS的产量和NOX2的表达量。然后对α-MHC-h D5F173L小鼠通过皮下给NADPH氧化酶的抑制剂罗布麻宁（Apocynin）4周,同时给PBS作为对照组,然后检测各项心肌病相关指标。同时构建人多巴胺D5受体突变基因（h D5F173L）和正常多巴胺D5受体基因（h D5WT）的大鼠心肌细胞（H9C2）,检测两者在基础条件下ROS产量的变化。结果α-MHC-h D5F173L转基因小鼠的NADPH氧化酶的活性和NOX2蛋白的表达量均明显高于野生型α-MHC-h D5WT小鼠,罗布麻宁能显著改善α-MHC-h D5F173L转基因小鼠的心脏功能。H9C2-h D5F173L大鼠细胞系NOX2的表达量及ROS产量高于H9C2-h D5WT对照细胞。结论多巴胺D5受体可能通过抑制氧化应激而防止扩张型心肌病的发生发展。

英文摘要：

Objective To determine whether dopamine D5 receptor（D5R） regulates the development of dilated cardiomyopathy（DCM） by inhibiting oxidative stress.Methods We developed heart-specific h D5 mutant（α-MHCh D5F173L） and wild type（α-MHC-h D5WT） transgenic mice.The NOX2 expression and ROS production were tested in the transgenic mice at three month of age.The α-MHC-h D5F173 L mice were treated with either NADPH oxidase inhibitor Apocynin（1mmol/kg/day） or phosphate-buffered saline（PBS） as control by intraperitoneal injection for 4 weeks.After then,the indexes of heart function were measured.The h D5WT and h D5F173 L were transfected respectively in rat H9C2 cells,in which ROS production and NOX2 expression were detected at basal level.Results The ROS production and NOX2 expression were higher in the heart of α-MHC-h D5F173 L than α-MHC-h D5WT mice.Apocynin treatment improved the heart function of α-MHC-h D5F173 L mice.NOX2 expression and ROS production were higher in h D5F173L than hD 5WT transfected H9C2 cells.Conclusions Dopomine D5 receptor may prevent DCM development by inhibiting oxidative stress.