五没食子酰葡萄糖靶向补体分子C1qa修复糖尿病小鼠主动脉内皮损伤的机制研究  

Mechanism of pentagalloylglucose targeted complement molecule C1qa for repairing endothelial damage in aorta of diabetic mice

作　　者：张安坤 李自成 陈佳妮 何冬旭 ZHANG Ankun;LI Zicheng;CHEN Jiani;HE Dongxu(School of Food Science and Technology,Jiangnan University,Wuxi 214122,China;School of Wuxi Medical University,Jiangnan University,Wuxi 214122,China)

机构地区：[1]江南大学食品学院,江苏无锡214122 [2]江南大学无锡医学院,江苏无锡214122

出　　处：《食品与发酵工业》2024年第17期66-74,共9页Food and Fermentation Industries

基　　金：国家自然科学基金面上项目(82070508)。

摘　　要：糖尿病常伴随血管内皮损伤,显著加速血管病理进程,但其分子机制尚未阐明。已有报道证实,特殊的补体分子在血管损伤中扮演重要角色。该实验室既往研究发现,补体分子C1qa(Component 1,q Subcomponent,A chain)在糖尿病小鼠主动脉内皮层高表达,并且表达量随着心血管疾病的发展而增多。因此,该研究利用链脲佐菌素(streptozocin,STZ)诱导糖尿病小鼠模型,并研究了C1qa分子的食源性抑制剂,即五没食子酰葡萄糖(1,2,3,4,6-O-pentagalloylglucose,PGG)对糖尿病血管内皮的修复作用。结果表明,外源C1qa刺激会显著增加血管内皮的活性氧(reactive oxygen species,ROS)水平,同时降低主动脉内皮依赖性舒张功能。相似地,糖尿病模型中,血管内皮C1qa的高含量伴随着ROS的过量合成,主动脉血管段的内皮依赖性舒张显著降低。而PGG灌胃3周后,糖尿病小鼠血糖下降至15.36 mmol/L,主动脉内皮C1qa表达量显著降低,ROS生成量减少了52.41%,血管内皮舒张率由47.06%升到68.41%。同时,NADPH氧化酶(NOX_(2)/NOX_(4))通路表达下调,提示ROS生成的关键通路被抑制,血管内皮氧化应激损伤显著减轻。因此,活性分子PGG靶向抑制C1qa,有利于修复糖尿病小鼠主动脉内皮损伤。Diabetes mellitus frequently causes endothelial damage,dramatically accelerating the progression of vascular diseases.However,the molecular mechanisms remain to be defined.Specific complement molecules have been demonstrated to play an important role in vascular injury.Previous research in our laboratory showed that the aortic endothelium of diabetic mice contained high levels of C1qa,which increased with the development of cardiovascular diseases.To investigate the effect of a dietary inhibitor of C1qa,1,2,3,4,6-O-pentagalloylglucose(PGG),on diabetic vascular endothelial repair,we established a streptozocin(STZ)diabetic mice model.Results showed that exogenous C1qa stimulation significantly increased vascular endothelial reactive oxygen species(ROS)levels while decreasing aortic endothelium-dependent diastolic function.Likewise,in diabetic mice,high vascular endothelial C1qa levels were associated with excessive ROS synthesis and significantly reduced endothelium-dependent diastole in aortic segments.Nevertheless,three weeks of PGG gavage in diabetic mice considerably reduced aortic endothelial C1qa expression,decreased blood glucose to 15.36 mmol/L,a 52.41%reduction in ROS production,and an increased rate in vascular endothelial diastolic from 47.06%to 68.41%.Simultaneously,PGG downregulated the expression of the NADPH oxidase pathway(NOX_(2)/NOX_(4)),indicating that it inhibited the essential pathway of ROS generation.Thus,vascular endothelial damage from oxidative stress got a substantial attenuation.Hence,PGG-targeted inhibition of C1qa is beneficial for repairing aortic endothelial dysfunction in diabetic mice.

关 键 词：五没食子酰葡萄糖 C1qa 主动脉内皮损伤 活性氧 NADPH 内皮依赖性舒张 

分 类 号：R587.1[医药卫生—内分泌] TS201.4[医药卫生—内科学]