大黄虫丸对家兔颈动脉粥样硬化斑块及MMP-9和VEGF表达影响
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摘要
目的:探讨大黄虫丸对家兔颈动脉粥样硬化斑块的干预及其对血管内基质金属蛋白酶9(MMP-9)和血管内皮生长因子(VEGF)表达的影响。方法:将40只正常健康的日本大耳白兔随机分为5组(空白对照组、模型对照组、阿托伐他汀钙片治疗组、大黄虫丸低剂量治疗组、大黄虫丸高剂量治疗组),雌雄各半,每组8只。普通饲料适应性饲养1周后,模型对照组及各治疗组采用右侧颈动脉内膜气体干燥损伤法造模,术后高脂饲料喂养,空白对照组普通饲料喂养。8周后处死家兔,切取右侧颈动脉1 cm,切片行HE染色,光镜下观察颈动脉组织病理学变化及免疫组织化学法检测斑块中MMP-9及VEGF的表达。结果:HE染色:空白对照组颈动脉内膜光滑、管腔均匀;模型组管壁增厚,管腔狭窄,提示动脉硬化形成;各治疗组与模型组比较,管壁结构大致正常,无明显畸形,提示药物干预成功。免疫组化:空白对照组颈动脉内膜MMP-9及VEGF阴性表达,其余各组表达阳性;各治疗组MMP-9及VEGF与模型对照组比较阳性表达明显降低,差异显著,具有统计学意义(P<0.01);大黄虫丸高剂量组MMP-9及VEGF阳性表达与阿托伐他汀钙片治疗组阳性表达相当(P>0.05)。结论:阿托伐他汀钙片与大黄虫丸均能调脂、稳定斑块、减少易损斑块,并降低颈动脉内MMP-9及VEGF的表达。
Objective:To investigate the effect of Dahuang Zhechong Pill on carotid atherosclerotic plaque in rabbits and its effect on the expression of matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)in blood vessels. Methods:40 normal Japanese rabbits were randomly divided into 5 groups(normal control group,model control group,Atorvastatin Calcium Tablets treatment group,Dahuang Zhechong Pill low-dose treatment group,Dahuang Zhechong Pill high-dose treatment group),male and female,8 in each group. One week after feeding the common feed,using the model group and each treatment group,lesions were created by air-drying isolated segments of the right carotid artery intima,fed with high-fat diet,and fed with normal diet in the control group. After 8 weeks,the rabbits were sacrificed and the right carotid artery was cut 1 cm. The sections were stained with HE. The pathological changes of the carotid artery were observed under optical microscope and MMP-9 and VEGF were detected by immunohistochemistry. Results:HE staining:In the control group,the carotid intima was smooth and the lumen was uniform;in the model group,the wall of the carotid artery was thickened and the lumen was narrowed,suggesting the formation of arteriosclerosis. Compared with the model group,the wall structure of the treatment group was generally normal and there was no obvious deformity. It indicated that the drug intervention was successful. Immunohistochemistry:The expression of MMP-9 and VEGF in the carotid intima was negative in the blank control group,and positive in the other groups. The positive expression of MMP-9 and VEGF in the treatment groups was significantly lower than that in the model control group,and the difference was statistically significant(P<0.01);The positive expression of MMP-9 and VEGF in the high-dose group of Dahuang Zhechong Pill was similar to that of the atorvastatin calcium group(P>0.05).Conclusions:Both Atorvastatin Calcium Tablets and Dahuang Zhechong Pill can regulate lipids,stabilize plaques,reduce vulnerable plaques,and reduce the expression of MMP-9 and VEGF in the carotid artery.
Objective:To investigate the effect of Dahuang Zhechong Pill on carotid atherosclerotic plaque in rabbits and its effect on the expression of matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)in blood vessels. Methods:40 normal Japanese rabbits were randomly divided into 5 groups(normal control group,model control group,Atorvastatin Calcium Tablets treatment group,Dahuang Zhechong Pill low-dose treatment group,Dahuang Zhechong Pill high-dose treatment group),male and female,8 in each group. One week after feeding the common feed,using the model group and each treatment group,lesions were created by air-drying isolated segments of the right carotid artery intima,fed with high-fat diet,and fed with normal diet in the control group. After 8 weeks,the rabbits were sacrificed and the right carotid artery was cut 1 cm. The sections were stained with HE. The pathological changes of the carotid artery were observed under optical microscope and MMP-9 and VEGF were detected by immunohistochemistry. Results:HE staining:In the control group,the carotid intima was smooth and the lumen was uniform;in the model group,the wall of the carotid artery was thickened and the lumen was narrowed,suggesting the formation of arteriosclerosis. Compared with the model group,the wall structure of the treatment group was generally normal and there was no obvious deformity. It indicated that the drug intervention was successful. Immunohistochemistry:The expression of MMP-9 and VEGF in the carotid intima was negative in the blank control group,and positive in the other groups. The positive expression of MMP-9 and VEGF in the treatment groups was significantly lower than that in the model control group,and the difference was statistically significant(P<0.01);The positive expression of MMP-9 and VEGF in the high-dose group of Dahuang Zhechong Pill was similar to that of the atorvastatin calcium group(P>0.05).Conclusions:Both Atorvastatin Calcium Tablets and Dahuang Zhechong Pill can regulate lipids,stabilize plaques,reduce vulnerable plaques,and reduce the expression of MMP-9 and VEGF in the carotid artery.
引文
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[15]李蕾.VEGF对血管内皮细胞基质金属蛋白酶ADAMTS5、ADAMTS4、MMP9表达的影响[D].济南:山东大学,2012.
[16]訾勇,张敏州,王磊,等.通冠胶囊对大鼠颈动脉球囊损伤术后血管内膜VEGF表达的影响[J].时珍国医国药,2009,20(9):2138-2140.
[17]洪艺云,叶胜难.MMP9及VEGF诱导血管生成在中耳胆脂瘤增殖与侵袭中的作用[J].中华耳科学杂志,2012,10(4):504-509.
[18]钟伟,王永刚,于远望,等.中医防治颈动脉粥样硬化的研究进展[J].中华中医药学刊,2017,35(8):2043-2045.
[19]周宇桢,卢健琪.中医药治疗动脉粥样硬化研究进展[J].湖南中医杂志,2017,33(4):169-171.
[20]万玲,王战义,魏星,等.经钛铝金属间化合物多孔材料筛选的大黄蛰虫丸抗动脉血栓形成的机制研究[J].中华中医药杂志,2013,28(12):3649-3653.
[21]江玉娟,孔令俊,张艳慧,等.大黄?虫丸对动脉粥样硬化大鼠血管保护作用的研究[J].中药药理与临床,2014,30(2):9-12.
[22]刘铁球,刘德军.神效良药大黄?虫丸[M].北京:中国中医药出版社,2002:110-151.
[2]李自超,王欣,马冬梅,等.脑梗死患者颈动脉粥样硬化斑块数量的影响因素[J].西安交通大学学报:医学版,2018(2):292-295.
[3]王新,李春阳,苏立平,等.动脉粥样硬化发病机制及治疗的研究进展[J].实用心脑肺血管病杂志,2017,25(2):1-4.
[4]李博萍,郑健龙.动脉粥样硬化与炎性反应的研究进展[J].临床合理用药杂志,2016,9(29):174-176.
[5]张东平.颈动脉粥样硬化的流行病学调查及临床研究[D].重庆:重庆医科大学,2009.
[6]郭恩会.阿托伐他汀对大鼠颈动脉粥样硬化易损斑块及hsCRP和MMP-9表达的影响[D].郑州:郑州大学,2017.
[7]张飞.VEGF及SiRNA和AP-2α对动脉粥样硬化斑块的影响[D].长沙:中南大学,2009.
[8]熊培政,冯雪梅,王芳.大黄?虫丸临床运用进展[J].亚太传统医药,2016,12(3):51-52.
[9]徐永革,周定标.颈动脉粥样硬化性狭窄动物模型的建立[J].中华神经外科杂志,2003,19(4):255-258.
[10]沈长银,石蓓.兔颈动脉粥样硬化狭窄动物模型的制备[J].四川大学学报(医学版)2009,40(5):923-926.
[11]Juan-Babot JO,Martinez-Gonzalez J,Berrozpe M,et al.Neovascularization in human coronary arteries with lesions of different severity[J].Rev Esp Cardiol,2003,56(10):978-986.
[12]Moreno P R,Purus hothaman K R,Sirol M,etal.Neovascularization in human atherosclerosis[J].Circulation,2006,113(18):2245-2252.
[13]Joseph D Raffetto,Raouf A Khalil.Matrixmetalloproteinases and their inhibitors in vascular remodeling and vascular disease[J].Biochemical Pharmacology,2008,75(2):346-359.
[14]Bar-Or A,Nuttall RK,Duddy M,et al.Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis[J].Brain,2003,126(12):2738-2749.
[15]李蕾.VEGF对血管内皮细胞基质金属蛋白酶ADAMTS5、ADAMTS4、MMP9表达的影响[D].济南:山东大学,2012.
[16]訾勇,张敏州,王磊,等.通冠胶囊对大鼠颈动脉球囊损伤术后血管内膜VEGF表达的影响[J].时珍国医国药,2009,20(9):2138-2140.
[17]洪艺云,叶胜难.MMP9及VEGF诱导血管生成在中耳胆脂瘤增殖与侵袭中的作用[J].中华耳科学杂志,2012,10(4):504-509.
[18]钟伟,王永刚,于远望,等.中医防治颈动脉粥样硬化的研究进展[J].中华中医药学刊,2017,35(8):2043-2045.
[19]周宇桢,卢健琪.中医药治疗动脉粥样硬化研究进展[J].湖南中医杂志,2017,33(4):169-171.
[20]万玲,王战义,魏星,等.经钛铝金属间化合物多孔材料筛选的大黄蛰虫丸抗动脉血栓形成的机制研究[J].中华中医药杂志,2013,28(12):3649-3653.
[21]江玉娟,孔令俊,张艳慧,等.大黄?虫丸对动脉粥样硬化大鼠血管保护作用的研究[J].中药药理与临床,2014,30(2):9-12.
[22]刘铁球,刘德军.神效良药大黄?虫丸[M].北京:中国中医药出版社,2002:110-151.