解毒活血中药配伍对载脂蛋白E基因敲除小鼠主动脉NF-κB与MMP-9表达的调控作用

Regulatory Effect of Chinese Herbal Compound for Detoxifying and Activating Blood Circulation on Expression of NF-κB and MMP-9 in Aorta of Apolipoprotein E Gene Knocked-out Mice

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中文关键词: 解毒活血配伍载脂蛋白E基因敲除小鼠核因子-κB 基质金属蛋白酶-9 动脉粥样硬化易损斑块芎芍胶囊

英文关键词:combined use of Chinese herbal medicines for detoxifying and activating blood circulation apolipoprotein E gene knocked-out mice nuclear factorκB matrix metalloproteinase-9 atherosclerosis vulnerable plaque Xiongshao Capsule

基金项目:国家中医药管理局中医药科学技术研究专项课题(No.0405JP64)

作者	单位
张京春	中国中医科学院西苑医院
陈可冀	中国中医科学院西苑医院
郑广娟	山东中医药大学
张文高	山东中医药大学
史大卓	中国中医科学院西苑医院
殷惠军	中国中医科学院西苑医院
刘龙涛	中国中医科学院西苑医院

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中文摘要:

目的观察解毒活血中药配伍对载脂蛋白E基因敲除小鼠[apolipoprotein E knocked-out mice, ApoE(-/-)mice]主动脉核因子-κB(NF-κB)和基质金属蛋白酶-9(MMP-9)表达水平的调控作用。方法13周龄ApoE(-/-)小鼠分为高脂组(给予高脂饲料)和普通饲料组(给予普通饲料),同时设13周龄C57 BL/6J小鼠对照组(给予普通饲料)。19周后进行干预,普通饲料模型组、C57BL/6J小鼠对照组灌服生理盐水,高脂组随机分为解毒组[灌服虎杖苷26．6 mg／(kg·d)],活血组[灌服芎芍胶囊110 mg／(kg·d)],解毒活血配伍高剂量组[灌服虎杖提取物53．2 mg／(kg·d),芎芍胶囊220 mg／(kg·d)];解毒活血配伍中剂量组[灌服虎杖提取物26．6 mg／(kg·d),芎芍胶囊110 mg／(kg·d)];解毒活血配伍低剂量组[灌服虎杖提取物13．3 mg／(kg·d),芎芍胶囊55 mg／(kg·d)],洛伐他汀组[灌服洛伐他汀3．3 mg／(kg·d)],高脂饲料模型组(灌服生理盐水)。17周后,取主动脉做常规石蜡切片,免疫组化观察其NF-κB和MMP-9表达的程度。结果模型组ApoE(-/-)小鼠主动脉及粥样斑块NF-κB和MMP-9表达明显增加,虎杖苷、芎芍胶囊、洛伐他汀及解毒活血配伍治则的虎杖苷与芎芍胶囊配伍均可降低其主动脉NF-κB和MMP-9表达(P<0．01),且以解毒活血配伍高剂量组疗效最好(P<0．01)。结论解毒活血配伍可降低ApoE(-/-)小鼠主动脉NF-κB和MMP-9表达,且优于单纯解毒和活血组。

英文摘要:

Objective To observe the regulatory effect of Chinese herbal compound for detoxifying and activating blood circulation on expression of nuclear factor-κB (NF-κB) and matrix metalloproteinase-9 (MMF-9) in aorta of apolipoprotein E gene knocked-out [ApoE (-/-)] mice. Methods ApoE (-/-) mice of 13-week old were divided into two groups and fed with normal diet (Group A) and hyperlipidemic diet (Group B) respectively, the latter was subdivided into 7 groups as Group B1 - 7. Besides, a normal control group was set up with C57BL/6J mice. The drugs used for intervention were polydatin (PD, with 26.6 mg/kg as one dose) for detoxifying and Xiongshao Capsule (XC, with 110 mg/kg as one dose) for activating blood circulation respectively. The intervention was started 19 weeks later by treated Group B1 with PD one dose daily, Group B2 with XC one dose daily, Group B3 with PD and XC each 2 doses daily, Group B4 with PD and XC each one dose daily, Group B5 with PD and XC each half dose daily, Group B6 with lovastatin. To the Group B 7 (as a hyperlipide-mia model group) as well as Group A and the normal control group, normal saline was given. After 17 weeks of intervention, the expressions of NF-κB and MMP-9 in aorta of mice were determined with immunohistochemical assay. Results Expressions of NF-κB and MMP-9 in aorta and sclerotic plaque were higher in group B7 than those in the normal control group, which were lowered in group B1-6(P<0.01), and the optimal effect was shown in group B3 (P<0.01). Conclusion Combined use of Chinese herbal medicine for detoxifying and activating blood circulation could reduce expression of NF-κB and MMP-9 in aorta of ApoE (-/-) mice, and the effect of the combination of the two was superior to that of use either of them.

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