基于CX3CL1介导的炎症反应研究淫羊藿苷对缺氧诱导的肺动脉高压小鼠的作用  

Effect of icariin on hypoxia-induced pulmonary hypertension in mice based on CX3CL1-mediated inflammation

作　　者：罗云梅 李铭铭 熊乙林 李利生 LUO Yun-mei;LI Ming-ming;XIONG Yi-lin;LI Li-sheng(Key Laboratory of Basic Pharmacology of Ministry of Education and International Cooperarion Joint Laboratory ofEthnomedicine of Ministry of Education,Zunyi Medical University,Zunyi 563000,China;Guizhou Key Laboratory of Basic Pharmacology,Department of Pharmacology,School of Pharmacy,Zunyi Medical University,Zunyi 563000,China;Department of Pharmacy,The Third Affiliated Hospital of Zunyi Medical University(The First People’s Hospital of Zunyi),Zunyi 563000,China)

机构地区：[1]遵义医科大学基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563000 [2]遵义医科大学贵州省基础药理重点实验室药学院药理学教研室,贵州遵义563000 [3]遵义医科大学第三附属医院(遵义市第一人民医院)药剂科,贵州遵义563000

出　　处：《中草药》2022年第4期1068-1075,共8页Chinese Traditional and Herbal Drugs

基　　金：遵义医科大学博士启动基金资助项目(F-951);遵义医科大学基础药理教育部重点实验室开放课题(JCYL-K-015);遵义市科技局与遵义医学院联合基金资助项目(遵市科合社字[2018]03号)。

摘　　要：目的研究淫羊藿苷改善缺氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)作用与趋化因子C-X3-C基元配体1(chemokine C-X3-C motif ligand 1,CX3CL1)介导的炎症反应的关系。方法将40只C57BL/6J雄性野生型(wide type,WT)小鼠随机分为对照组、WT模型组和WT+淫羊藿苷(10、20 mg/kg)组,20只雄性CX3CL1-/-小鼠分为CX3CL1-/-模型组和CX3CL1-/-+淫羊藿苷(20 mg/kg)组。除对照组外,各组均于含氧量为10%的低氧环境中连续饲养21 d,于低氧饲养7 d后ig淫羊藿苷2周。采用小动物超声仪检测小鼠肺动脉血流速度和右心室血流动力学,测量右心室肥厚指数(right ventricular hypertrophy index,RVHI);采用苏木素-伊红(HE)和Masson染色观察小鼠肺小动脉重构情况;采用ELISA法检测小鼠血清中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-1β(interleukin-1β,IL-1β)水平;采用Western blotting检测小鼠肺组织CX3CL1和核因子-κB(nuclear factor-κB,NF-κB)通路相关蛋白表达情况。结果与对照组相比,WT模型组小鼠肺动脉血流速度明显降低(P<0.05),RVHI显著增大(P<0.05),右心室收缩末期直径、收缩末期容积和每博输出量升高(P<0.05),右心室短轴缩短率和射血分数降低(P<0.05),肺小动脉重构明显。与WT模型组相比,淫羊藿苷能够增加WT小鼠肺动脉血流速度(P<0.05),降低RVHI、右心室收缩末期直径、收缩末期容积和每博输出量(P<0.05),升高右心室短轴缩短率和射血分数(P<0.05),肺小动脉重构明显改善,同时,淫羊藿苷降低血清IL-1β和TNF-α水平以及肺组织CX3CL1蛋白表达水平(P<0.05),抑制NF-κB通路相关蛋白表达水平(P<0.05)。与WT模型组相比,CX3CL1-/-模型组小鼠肺动脉血流速度、肺小动脉重构、右心室血流动力学均有改善(P<0.05),血清IL-1β和TNF-α水平降低(P<0.05)。敲除CX3CL1-/-后,淫羊藿苷(20 mg/kg)对HPH小鼠的改善作用减弱甚至消失。结论淫羊藿苷能够通过抑制CX3CL1介导的炎症Objective To study the relationship between ameliorative effect of icariin on hypoxic pulmonary hypertension(HPH)and inflammation mediated by chemokine chemokine C-X3-C motif ligand 1(CX3CL1).Methods Forty C57BL/6J male wild type(WT)mice were randomly divided into control group,WT model group and WT+icariin(10,20 mg/kg)group;And twenty male CX3CL1−/−mice were divided into CX3CL1−/−model group and CX3CL1−/−+icariin(20 mg/kg)group.Except for control group,mice were exposed to hypoxia environment with oxygen content of 10%for 21 d,and were ig icariin for two weeks after 7 d of hypoxic feeding.Pulmonary artery blood flow velocity and right ventricular hemodynamics of mice were detected by ultrasound,and right ventricular hypertrophy index(RVHI)was measured;HE and Masson staining were used to observe the remodeling of pulmonary artery;Tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)levels in serum was detected by ELISA;Western blotting was used to detect CX3CL1 and nuclear factor-κB(NF-κB)pathway-related protein expressions in lung of mice.Results Compared with control group,pulmonary artery blood flow velocity of mice in WT model group was significantly decreased(P<0.05),RVHI was significantly increased(P<0.05),right ventricular end-systolic diameter,end-systolic volume and output per stroke were increased(P<0.05),right ventricular short axis shortening rate and ejection fraction were decreased(P<0.05),and pulmonary arteriole remodeling was obvious.Compared with WT model group,pulmonary artery blood flow velocity of mice was increased by icariin(P<0.05),RVHI,right ventricular end-systolic diameter,end-systolic volume and output per stroke were reduced(P<0.05),right ventricular short axis shortening rate and ejection fraction were increased(P<0.05),and pulmonary arteriole remodeling was significantly improved;IL-1βand TNF-αlevels in serum and CX3CL1 protein expression in lung tissue were decreased by icariin(P<0.05),NF-κB pathway related protein expressions were inhibited(P<0.05).Compared w

关 键 词：淫羊藿苷 趋化因子C-X3-C基元配体1 炎症 缺氧性肺动脉高压 小鼠 

分 类 号：R285.5[医药卫生—中药学]