三七皂苷R1对LPS诱导的小鼠心肌损伤的保护作用  

Protective effect of Notoginesenoside R1 on lipopolysaccharide-induced myocardial dysfunction in mice

作　　者：吴颖[1] 孙冰[2] 肖静[2] 孙桂波[2] 吕圭源[3] 李明[1] 陈素红[1] 孙晓波[2] 

机构地区：[1]温州医学院药学院浙江温州325035 [2]中国医学科学院药用植物研究所北京100193 [3]浙江中医药大学中药研究所浙江杭州310053

出　　处：《中国药理学通报》2013年第2期179-184,共6页Chinese Pharmacological Bulletin

基　　金：国家科技支撑计划课题(No 2008BAI51B00);国家重大新药创制科技专项(No 2012ZX09501001,2012ZX09301002-001)

摘　　要：目的探讨三七皂苷R1(Notoginsenoside R1)对内毒素诱导的C57BL/6J小鼠心肌损伤的保护作用,阐明其抗心肌炎症的作用机制。方法 C57BL/6J小鼠预防性给予三七皂苷R1 3 d后,注射LPS(10 mg.kg-1,ip)建立急性内毒素心肌损伤模型。采用超声心动测定射血分数(EF),缩短分数(FS)等指标,观察小鼠心功能;采用免疫组化检测心室肌中ED-1+和CD11b+炎性细胞的浸润情况;Western blot检测IκBα和NF-κB p65的表达变化;应用酶联免疫吸附测定法(ELISA)检测心肌组织匀浆中TNF-α、IL-1β和VCAM-1、ICAM-1的表达水平。结果超声心动显示,与模型组(LPS组)相比三七皂苷R1能明显抑制LPS诱导的小鼠的左心室收缩功能减弱的情况;免疫组化可观察到R1有效抑制了ED-1+和CD11b+细胞的侵入;Western blot法显示R1对IκBα的降解具有抑制作用,同时对由此产生的NF-κB的活化也具有抑制作用;ELISA实验显示与模型组相比,R1明显降低了组织中TNF-α、IL-1β的浓度,抑制心肌组织中VCAM-1和ICAM-1的表达。结论三七皂苷R1对LPS引起的心肌炎症具有明显的抑制作用,能有效改善由此导致的心肌损伤。Aim To examine the effects of Notoginesenoside R1 on lipopolysaccharide-induced myocardial dysfunction in mice and to evaluate the anti-inflamma-tory properties of Notoginesenoside R1.Methods C57BL/6J mice（8 per group） were pretreated with Notoginesenoside R1 for 3 days.Mice were treated with LPS（10 mg·kg^-1,ip）for 8h to establish an acute cardiac injury model induced by endotoxin.The cardiac echocardiography was used to measure the indexes of ejection fraction（EF）,fractional shortening（FS）;infiltrations of ED-1 and CD11b in postcapillary venules were quantified by immunohistochemical analysis;the protein levels of IκBα and NF-κB p65 were detected with Western blot analysis;the expressions of TNF-α,IL-1β,VCAM-1 and ICAM-1 in cardiac myocytes were respectively measured with enzyme-linked immunoadsorbent assay（ELISA） kits.Results Cardiac echocardiographic assay revealed that LPS induced a marked depression of left ventricular contractility which was significantly inhibited by Notoginesenoside R1 compared with normal control group.Immunohistochemical staining for ED-1 and CD11b demonstrated that Notoginesenoside R1 prevented local recruitment of monocytes and polymorph nuclear neutrophils to the myocardium.Western blot analysis indicated that Notoginesenoside R1 inhibited degradation of IκBα,accordingly showed the inactivation of transcription factor nuclear factor-κB.Accordingly,Notoginesenoside R1 prevented LPS-induced elevation of myocardial tissue necrosis factor-α and IL-1β,while R1 reduced ICAM-1 and VCAM-1 expression.Conclusions Notoginesenoside R1 markedly inhibits the myocarditis induced by LPS and remedies subsequent myocardial dysfunction.

关 键 词：三七皂苷R1 LPS 心肌损伤 抗炎 CD11B NF-κB TNFΑ 

分 类 号：R-332[医药卫生] R284.1