龙生蛭胶囊对ApoE^(-/-)小鼠动脉粥样硬化的干预作用及机制探讨  

Effect and Mechanism of Longshengzhi Capsule on Atherosclerosis in ApoE^(-/-)Mice

作　　者：孙晓丽 肖燕霞[1] 付帮泽 杨天潇 刘俊杰 王伟 SUN Xiao-li;XIAO Yan-xia;FU Bang-ze;YANG Tian-xiao;LIU Jun-jie;WANG Wei(Department of Biological Medicine of Beijing City University,Beijing 100094,China;Beijing University of Chinese Medicine,Beijing 100029,China;Nanjing Pukou Hospital of Traditional Chinese Medicine,Nanjing 211800,China;Guangzhou University of Chinese Medicine,Guangzhou 510006,China)

机构地区：[1]北京城市学院生物医药学部,北京100094 [2]北京中医药大学,北京100029 [3]南京浦口中医院,南京211800 [4]广州中医药大学,广州510006

出　　处：《中国实验方剂学杂志》2022年第6期86-91,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：北京城市学院“城市新星计划”训练项目(202111418015);北京中医药大学校企合作项目(218007170034)。

摘　　要：目的:研究龙生蛭胶囊(LSZC)对高脂饮食诱导的载脂蛋白E敲除(ApoE^(-/-))小鼠动脉粥样硬化(AS)的干预作用。方法:高脂饮食喂养8周建立ApoE^(-/-)小鼠AS模型后,随机分为辛伐他丁组(4 mg·kg^(-1))、龙生蛭胶囊高、中、低剂量组(1.6、0.8、0.4 g·kg^(-1)),同时设置正常组(C57BL/6J小鼠,普通饲料喂养)。实验结束,通过苏木素-伊红(HE)和油红O染色观察AS病变后主动脉病理形态变化;并检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDLC)、丙二醛(MDA)、总超氧化物歧化酶(SOD)、白细胞介素-1β(IL-1β)、IL-6水平的变化;免疫组化(IHC)法测定主动脉CD34,F4/80的水平。结果:与正常组比较,模型组血清TC、TG、LDL-C、HDL-C、MDA、IL-1β和IL-6含量显著升高(P<0.01),SOD水平显著降低(P<0.01),主动脉出现明显斑块与脂质堆积,内膜破坏严重,CD34、F4/80表达量显著增加(P<0.01)。与模型组比较,龙生蛭胶囊低、中、高剂量组小鼠血清中TG、LDL-C含量均明显降低(P<0.05),主动脉斑块面积减小。龙生蛭胶囊高、中剂量组明显提高SOD水平,降低MDA水平(P<0.05,P<0.01);龙生蛭胶囊各剂量组均明显降低IL-1β和IL-6的水平(P<0.05,P<0.01)。龙生蛭胶囊高、中剂量组血管CD34、F4/80阳性染色的表达量明显减少(P<0.05,P<0.01)。结论:龙生蛭胶囊对ApoE^(-/-)小鼠AS主动脉斑块形成有一定的干预作用,其机制可能与降低血清TG、LDL-C水平发挥降血脂作用、提高SOD水平,降低MDA水平发挥脂质过氧化损伤、降低IL-1β、IL-6的水平和抑制动脉血管CD34、F4/80表达保护血管免受炎症损伤有关。Objective: To study the effect of Longshengzhi capsule(LSZC)on high fat diet(HFD)-induced atherosclerosis(AS)in apolipoprotein E knockout(ApoE^(-/-))mice. Method:ApoE^(-/-)mice were fed with HFD for 8 weeks to induce AS. Then the mice were randomized into model group, simvastatin group(4 mg·kg^(-1)),high-dose LSZC group(1.6 g·kg^(-1)),medium-dose LSZC group(0.8 g·kg^(-1)),and low-dose LSZC group(0.4 g·kg^(-1)). C57BL/6J Mice with normal diet were used as the blank control. After 10 weeks,serum levels of triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),malondialdehyde(MDA),superoxide dismutase(SOD),interleukin-1β(IL-1β),and interleukin-6(IL-6)were detected. Hematoxylin-eosin(HE)and oil red O were used to detect aortic plaque in each group. The levels of CD34 and F4/80 in aorta were determined by immunohistochemistry(IHC).Result: Compared with the blank control,the model group demonstrated obvious aortic plaque,a large amount of lipid accumulation,serious damage of aortic intima,increase in serum levels of TC,TG,LDL-C,HDL-C,MDA,IL-1β,and IL-6(P<0.01),decrease in SOD level(P<0.01),and rise of the expression of CD34 and F4/80(P<0.01). Compared with the model group,LSZC of the three doses all decreased the serum levels of TG and LDL-C(P<0.05),and the levels of IL-1β and IL-6(P<0.05,P<0.01),and the high-dose and medium-dose LSZC improved SOD level,decreased MDA content(P<0.05,P<0.01),and reduced the expression of the CD34 and F4/80 in blood vessels(P<0.05,P<0.01). Conclusion: LSZC has certain intervention effect on the formation of aortic plaque in atherosclerosis ApoE^(-/-)mice. The mechanism is that it reduces the levels of serum TG and LDL-C to lower blood lipid, decreases MDA level and improves SOD activity to inhibit lipid peroxidation,lowers the levels of IL-1β and IL-6 and down-regulates the expression of CD34 and F4/80 to protect blood vessels from inflammatory damage.

关 键 词：龙生蛭胶囊 载脂蛋白E敲除(ApoE^(-/-))小鼠 动脉粥样硬化 主动脉斑块 脂质堆积 

分 类 号：R2-0[医药卫生—中医学] R22