抗炎抗凝融合蛋白TAP-SSL5对ApoE基因敲除小鼠动脉粥样硬化病变形成的影响  

Effect of Fusion Protein TAP-SSL5 on Atherosclerotic Plaque Formation in ApoE Knockout Mice

作　　者：曲小龙[1] 孟璟[1] 胡厚源[1] Qu Xiaolong Meng Jing Hu Houyuan(Department of Cardiology, Southwest Hospital,Third Military Medical University, Chongqing 400038, Chin)

机构地区：[1]第三军医大学西南医院心血管内科,重庆400038

出　　处：《中国药师》2017年第6期974-978,共5页China Pharmacist

基　　金：国家高技术研究发展(863)计划项目(编号:2009AA02Z115);国家科技重大新药创制项目(编号:2013ZX09103003)

摘　　要：目的:探讨重组融合蛋白蜱抗凝血肽(TAP)-金黄色葡萄球菌超抗原样蛋白5(SSL5)对Apo E基因敲除(Apo E^(-/-))小鼠动脉粥样硬化病变形成的影响。方法:选取12周龄雄性Apo E^(-/-)小鼠21只,随机分为3组:TAP-SSL5组(3 mg·kg^(-1)·d^(-1))、SSL5组(2 mg·kg^(-1)·d^(-1))、空白对照组(p H 7.4磷酸盐缓冲液),ip,qd,连续给药12周,观察小鼠体质量变化。高脂饮食饲养12周后取材,检测血浆总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平;对小鼠主动脉血管进行石蜡切片,常规HE染色,分析小鼠主动脉根部血管动脉粥样硬化斑块的形成情况,小鼠主动脉内膜面采用油红O染色,比较动脉粥样硬化斑块的分布情况。结果:高脂饲养12周后,与空白对照组比较,TAP-SSL5组小鼠体质量增长和TC水平明显降低(P<0.001),而TG、HDL-C、LDL-C水平无明显变化。HE染色结果表明,TAP-SSL5组主动脉根部切片斑块面积明显降低(P<0.05);主动脉大体标本斑块油红O染色提示TAP-SSL5干预组主动脉动脉粥样硬化斑块形成明显小于空白对照组。结论:TAP-SSL5可显著抑制Apo E^(-/-)小鼠动脉血管粥样硬化斑块的形成。Objectives. To investigate the effect of fusion protein tick anticoagulant peptide （TAP） - staphylococcus aureus supe- rantigen-like protein 5 （SSLS） on the formation of atherosclerotic plaque in ApoE knockout （ApoE-/- ） mice. Methods： Totally 21 male 12-week-old ApoE-/- mice were randomly divided into three groups： TAP-SSL5 （3 mg · kg-1 · d-1 ） group, SSL5 （2 mg · kg-1 · d-1 ） group and the blank control group （ pH 7.4 phosphate buffer）, ip, qd, for 12 weeks. The changes of body mass were ob- served. The mice were fed with high cholesterol diet for 12 weeks, and then the levels of total cholesterol （TC） , triglyceride （TG） , high density lipoprotein cholesterol （HDL-C） and low density lipoprotein cholesterol （LDL-C） in plasma were detected. The aorta of mice was subjected to paraffin section and routine HE staining. The formation of atherosclerotic plaque in the aortic root was analyzed. The distribution of atherosclerotic plaques was observed by oil red O staining of the aorta. Results： Compared with that of the blank control group, the increasement of body weight of TAP-SSL5 group and the level of TC significantly decreased （ P 〈 0.001 ）, while TG, HDL-C and LDL-C did not change significantly. The HE staining results showed that the plaque area of root slice in the aorta in TAP-SSL5 group was significantly lower than that in the blank control group （P 〈 0.05）. The red O staining of aorta showed that the formation of atherosclerotic plaque in TAP-SSL5 group was siguificantly smaller than that in the blank control group. Conclusion： TAP- SSL5 can significantly inhibit the formation of atherosclerotic plaques in the arteries of ApoE -/- mice.

关 键 词：金黄色葡萄球菌超抗原样蛋白5 蜱抗凝血肽 炎症 动脉粥样硬化 APOE基因敲除小鼠 

分 类 号：R965.1[医药卫生—药理学]