参附注射液经NOS/NO通路改善血管性痴呆小鼠认知功能障碍的实验研究  

Shenfu injection improves cognitive dysfunction in vascular dementia model mice via the NOS/NO pathway

作　　者：饶思静 张森 邵亚兰 洪芬芳[2] 杨树龙[1,3,4,5] RAO Sijing;ZHANG Sen;SHAO Yalan;HONG Fengfang;YANG Shulong(Department of Physiology,College of Basic Medicine,Nanchang University,Nanchang 330006,China;Pathogen Biology Experimental Center,Nanchang University,Nanchang 330006;Department of Physiology,Fuzhou Medical College,Nanchang University,Fuzhou 344099;Key Laboratory of Chronic Diseases,Fuzhou Medical College,Nanchang University,Fuzhou 344099;Technology Innovation Center of Chronic Disease Research in Fuzhou City,Fuzhou Science and Technology Bureau,Fuzhou 344000)

机构地区：[1]南昌大学基础医学院生理学教研室,南昌330006 [2]南昌大学基础医学院病原生物学实验中心,南昌330006 [3]南昌大学抚州医学院生理学教研室,江西抚州344099 [4]南昌大学抚州医学院慢性病研究重点实验室,江西抚州344099 [5]抚州市慢性病研究技术创新中心,江西抚州344000

出　　处：《中国比较医学杂志》2023年第6期8-15,共8页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(82060661,81660151,81660751);江西省自然科学基金项目(20212BAB206092);江西省教育厅科技研究重点项目(GJJ218104)。

摘　　要：目的研究参附注射液改善血管性痴呆小鼠认知功能障碍的作用机制。方法雄性昆明系小鼠,分为假手术组、模型组(VD)、参附注射液组(SFI,10 mL/kg)、一氧化氮前体组(L-Arg,25 mg/kg)、一氧化氮合酶抑制剂组(L-NAME,10 mg/kg),每组各9只。双侧颈总动脉重复夹闭和再灌注以及腹腔注射硝普钠复制VD小鼠模型,造模成功后各组分别给药21 d,假手术组和VD组小鼠腹腔注射等量生理盐水。Morris水迷宫检测小鼠学习记忆能力;HE和Nissl染色观察海马组织病理学改变;Griess法测定NO浓度;ROS、MDA、GSH含量应用试剂盒检测;Western blot检测nNOS、iNOS、eNOS蛋白表达。结果与假手术组相比,VD组小鼠Morris迷宫实验中潜伏时间延长,学习、记忆能力降低,海马CA1区域病理损伤明显,NO、ROS、MDA含量升高,GSH活性降低(P<0.01,P<0.05),nNOS、iNOS蛋白表达均显著升高,eNOS蛋白表达降低(P<0.01,P<0.05)。与VD组相比,L-Arg用药组小鼠学习记忆能力,海马CA1区域病理损伤,NO、ROS、MDA、GSH表达等均无明显改善。而SFI及L-NAME用药组可观察到小鼠学习记忆能力较VD组有所改善,海马CA1区域病理损伤明显改善,NO、ROS、MDA含量降低,GSH活性升高,eNOS蛋白表达升高,iNOS、nNOS蛋白表达明显降低(P<0.01,P<0.05)。结论SFI改善VD小鼠认知功能障碍可能与NOS/NO通路有关。Objective To explore the mechanism of Shenfu injection improving cognitive dysfunction in vascular dementia model mice.Methods Male Kunming mice were randomly divided into a Sham operation group,VD model group,SFI group(10 mL/kg),L-Arg group(25 mg/kg),and L-NAME group(10 mg/kg)with nine in each group.The VD mouse model was established by repeated clipping and reperfusion of bilateral common carotid arteries and intraperitoneal injection of sodium nitroprusside.After modeling,each group was administered drugs for 21 days,and Sham operation and VD model groups were administered the same amount of physiological saline.The Morris water maze test assessed learning and memory abilities of mice,HE and Nissl staining was used to observe pathological changes.The Griess method was used to assess the NO concentration.ROS,MDA,and GSH contents were assessed by kits.iNOS,nNOS,and eNOS protein expression was assessed by Western blot analysis.Results Compared with the Sham operation group,the latency time of the VD group was prolonged in the Morris maze test,pathological damage in the hippocampal Ca1 region was obvious,NO,ROS,and MDA contents were increased,GSH activity was decreased(P<0.01,P<0.05),nNOS and iNOS expression was significantly increased,and eNOS protein expression was decreased(P<0.01,P<0.05).Compared with the VD group,L-Arg treatment group showed no significant improvements in learning or memory abilities,pathological damage in the hippocampal CA1 region,or expression of NO,ROS,MDA,and GSH.Compared with the VD group,learning and memory abilities in SFI and L-NAME groups were improved,pathological damage of the hippocampal Ca1 region was significantly improved,NO,ROS,and MDA contents were decreased,GSH activity was increased,eNOS protein expression was increased,and iNOS and nNOS protein expression was significantly decreased(P<0.01,P<0.05).Conclusions SFI improves cognitive dysfunction in VD mice,which may be related to the NOS/NO pathway.

关 键 词：参附注射液 血管性痴呆 一氧化氮 一氧化氮合酶 认知功能 

分 类 号：R-33[医药卫生]