生物活性脂类淫羊藿苷和卡里丁通过调节炎症基因和可塑性相关基因蛋白1促进脑卒中神经功能恢复的机制  

Mechanism of bioactive lipids icariin and caridin on promoting neurofunctional recovery via regulating inflammatory genes and plasticity related gene 1 after stroke

作　　者：冯鹏超 周利飞 靳文艳 FENG Pengchao;ZHOU Lifei;JIN Wenyan(The Second Affiliated Hospital of Hebei North University,Zhangjiakou 075100,China)

机构地区：[1]河北北方学院附属第二医院,张家口075100

出　　处：《西北药学杂志》2025年第2期87-94,共8页Northwest Pharmaceutical Journal

基　　金：河北省中医药管理局科研计划项目(编号:2024325)。

摘　　要：目的探讨生物活性脂类调节炎症基因和可塑性相关基因蛋白1(plasticity related gene 1,PRG-1)促进脑卒中神经功能恢复的机制。方法将小鼠(n=30)随机分为5组:假手术组、大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)小鼠模型组、MCAO联合依达拉奉组、MCAO联合淫羊藿苷(icariin,ICA)组和MCAO联合卡里丁(caridin,ICT)组。比较各组神经学评分,进行梗死体积的测定和组织病理学检测,用Tunel测定晚期凋亡细胞的DNA片段,用蛋白质印迹法分析凋亡蛋白(cleavedcaspase-3、cleaved-PARP、Bcl-2和Bax)、炎症基因(catalase、SOD1、caveolin-1、e-NOS和i-NOS)和PRG-1,用TBARS检测试剂盒检测MDA的水平。结果MCAO组体质量(19.56%±2.65%)减轻、梗死体积(占对侧面积百分比)(63.12%±3.05%)和mNSS评分[(12.32±1.13)分]均显著增加,ICA治疗后,小鼠体质量(9.51%±1.61%)、梗死面积(6.51%±1.21%)、mNSS(3.51±1.01)显著降低;ICT治疗后,小鼠体质量(7.51%±1.61%)、梗死体积(5.55%±1.21%)、mNSS(3.01±1.21)显著降低。在MCAO小鼠的脑海马体和皮层中明显观察到Tunel阳性细胞,经ICA和ICT治疗均可有效逆转。MCAO组皮质和海马体中裂解半胱天冬酶-3(3.78±3.05)(16.72±2.19)、裂解PARP(4.12±3.11)(3.82±3.95)和Bax(5.92±2.15)(3.52±1.15)的蛋白表达水平均显著升高,而MCAO组皮质和海马体中Bcl-2蛋白(0.12±0.05)(0.31±0.09)的表达水平均显著降低。ICA治疗后,小鼠皮质和海马体中裂解半胱天冬酶-3(1.54±0.61)(6.21±1.01)、Bax(2.12±0.67)(0.98±0.85)显著降低、Bcl-2蛋白(0.51±0.11)水平显著升高。ICT治疗后,小鼠皮质和海马体中裂解半胱天冬酶-3[(1.31±1.11)(4.52±1.21)]、Bax[(2.12±0.85)(1.08±0.25)]均显著降低、Bcl-2蛋白(0.51±0.06)水平显著升高。MCAO小鼠皮层和海马体中过氧化氢酶(0.68±0.07)(0.42±0.19)和SOD-1[(0.44±0.08)(0.47±0.11)]的蛋白表达水平显著降低,用ICA和ICT处理均显著逆转了SOD-1蛋白表达水平的降低,同时部分逆�Objective To investigate the mechanism by which bioactive lipids regulate inflammatory genes and plasticity-related gene 1(PRG-1)to promote neurofunctional recovery after stroke.Methods Mice(n=30)were randomly divided into 5 groups:sham surgery group,middle cerebral artery occlusion(MCAO)model group,MCAO combined with edaravone group,MCAO combined with icariin(ICA)group,and MCAO combined with caridin(ICT)group.Neurological scores were compared among the groups,infarct volume was measured,and histopathological examinations were conducted.Tunel staining was used to detect late apoptotic cells by DNA fragmentation.Western blotting was employed to analyze apoptotic proteins(cleaved-caspase-3,cleaved-PARP,Bcl-2,and Bax),inflammatory genes(Catalase,SOD1,Caveolin-1,e-NOS,and i-NOS),and PRG-1.The levels of malondialdehyde(MDA)were detected using a TBARS assay kit.Results The MCAO group exhibited significant increases in body weight loss(19.56%±2.65%),infarct volume(63.12%±3.05%of contralateral area),and modified neurological severity score(mNSS)[12.32±1.13].After ICA treatment,the body weight loss(9.51%±1.61%),infarct area(6.51%±1.21%),and mNSS(3.51±1.01)were significantly reduced.Similarly,ICT treatment led to significant reductions in body weight loss(7.51%±1.61%),infarct volume(5.55%±1.21%),and mNSS(3.01±1.21).Tunel-positive cells were prominently observed in the hippocampus and cortex of MCAO mice,which were effectively reversed by ICA and ICT treatments.In the MCAO group,protein expression levels of cleaved-caspase-3[(3.78±3.05)in cortex,(16.72±2.19)in hippocampus],cleaved-PARP[(4.12±3.11)in cortex,(3.82±3.95)in hippocampus],and Bax[(5.92±2.15)in cortex,(3.52±1.15)in hippocampus]were significantly elevated,while Bcl-2 protein levels[(0.12±0.05)in cortex,(0.31±0.09)in hippocampus]were significantly decreased.ICA treatment significantly reduced cleaved-caspase-3[(1.54±0.61)in cortex,(6.21±1.01)in hippocampus]and Bax[(2.12±0.67)in cortex,(0.98±0.85)in hippocampus]levels,while increasing Bcl-2 prote

关 键 词：生物活性脂类 淫羊藿苷 卡里丁 炎症基因 可塑性相关基因蛋白1 脑卒中 神经功能 

分 类 号：R96[医药卫生—药理学]