双降汤联合阿托伐他汀对颈动脉粥样硬化患者斑块的影响及其机制研究
Effect of Shuangjiang Decoction on Carotid Atherosclerotic Plaque
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摘要: 目的 观察双降汤联合阿托伐他汀对颈动脉粥样硬化患者的临床疗效及作用机制。方法 107例颈动脉粥样硬化斑块气虚痰瘀证患者随机分成4组。基础治疗为受试者均采用低盐低脂饮食,硬斑块1组及软斑块1组每日口服阿托伐他汀20 mg,硬斑块2组及软斑块2组在每天口服阿托伐他汀20 mg的基础上,加双降汤,每日1剂口服,各组均连续服用12周。观察各组患者治疗前后血清单核细胞趋化蛋白-1(MCP-1)、巨噬细胞移动抑制因子(MIF)、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-9(MMP-9)、核转录因子κBp65(NF-κBp65)、转化生长因子β1(TGF-β1)水平,斑块面积及中医证候积分。结果 各组患者血清中均见较高水平的细胞炎症因子MCP-1、MIF、NF-κBp65、TGF-β1及蛋白酶MMP-1、MMP-9表达。与治疗前硬斑块1组及硬斑块2组加双降汤比较,软斑块1组及软斑块2组加双降汤患者血清中MCP-1、MIF、NF-κBp65、MMP-1、MMP-9水平升高,而TGF-β1水平降低(P<0.01)。与本组治疗前比较,硬斑块1组及软斑块1组患者血清中MCP-1、MIF、NF-κBp65、MMP-1、MMP-9水平升高,而TGF-β1水平降低(P<0.05),硬斑块2组加双降汤及软斑块2组加双降汤变化尤为显著(P<0.01)。与治疗后硬斑块2组加双降汤比较,软斑块2组加双降汤MCP-1、MIF、NF-κBp65、MMP-1、MMP-9水平升高,而TGF-β1水平降低(P<0.05)。与治疗前比较,硬斑块1组及软斑块1组颈动脉斑块面积缩小(P<0.05),硬斑块2组加双降汤及软斑块2组加双降汤颈动脉斑块面积缩小(P<0.01),且软斑块2组加双降汤颈动脉斑块面积缩小优于硬斑块2组加双降汤(P<0.05)。治疗后各组均能降低中医证候积分,与硬斑块1组及软斑块1组比较,硬斑块2组加双降汤及软斑块2组加双降汤能明显降低颈动脉粥样硬化患者中医证候积分(P<0.05)。结论 细胞炎症因子MCP-1、MIF、NF-κBp65、TGF-β1及蛋白酶MMP-1、MMP-9参与颈动脉粥样硬化的形成的调控,双降汤及阿托伐他汀可有效缩小颈动脉斑块面积及明显改善颈动脉斑块患者中医证候,二者联合应用疗效更佳,能其机制可能与降低患者血清MCP-1、MIF、MMP-1、MMP-9、NF-κBp65水平,升高血清TGF-β1水平有关。Abstract: OBJECTIVE To observe effect of Shuangjiang Decoction combined with atorvastatin on carotid atherosclerotic plaque. METHODS 107 patients with carotid atherosclerotic plaque were randomly divided into four groups. The basic treatment was based on low-salt and low-fat diet. The hard-plaque group 1 and soft-plaque group 1 were treated with oral atorvastation daily 20 mg, while hard-plaque group 2 and soft-plaque group 2 were given Shuangjiang Decoction on the basis of 20 mg of atorvastation. One dose per day orally, each group was continuously taken for 12 weeks. The serum monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor (MIF), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-9 (MMP-9), nuclear factor-κBp65 (NF-κBp65), transforming growth factor-β1(TGF-β1) levels, plaque area and TCM syndrome scores of two groups were observed before and after treatment. RESULTS High levels of cellular inflammatory factors MCP-1, MIF, NF-κBp65, TGF-β1 and proteases MMP-1 and MMP-9 were observed in the serum of each group. Compared with hard-plaque group 1 and 2 with Shuangjiang Decoction before treatment, the level of MCP-1, MIF, NF-κBp65, MMP-1, MMP-9 in soft-plaque group 1 and 2 with Shuangjiang Decoction were higher, while TGF-β1 levels were decreased (P<0.01). Compared with the pre-treatment group, the level of MCP-1, MIF, NF-κBp65, MMP-1, MMP-9 in the serum of hard-plaque group 1 and soft-plaque group 1 were increased, while the level of TGF-β1 was decreased (P<0.05). The changes of hard-plaque group 2 and soft-plaque group 2 with Shuangjiang Decoction were especially significant(P<0.01). Compared with hard-plaque group 2 with Shuangjiang Decoction after treatment, the levels of MCP-1, MIF, NF-κBp65, MMP-1 and MMP-9 in soft-plaque group 2 with Shuangjiang Decoction were increased, while the level of TGF-β1 was decreased (P<0.05). Compared with pre-treatment, the area of carotid plaque in group 1 of hard-plaque and soft-plaque group 1 was reduced (P<0.05), and in group 2 of hard-plaque and soft-plaque with Shuangjiang Decoction was also reduced (P<0.01). The area of the cartoid plaque in soft-plaque group 2 with Shuangjiang Decoction was better than that in hard-plaque group 2 with Shuangjiang Decoction (P<0.05). After treatment, each group can reduce the TCM syndrome scores. Compared with the hard-plaque group 1 and soft-plaque group 1, the hard-plaque group 2 and soft-plaque group 2 with Shuangjiang Decoction can significantly reduce TCM syndrome scores in patients with carotid atherosclerosis (P<0.05). CONCLUSION Cytoinflammatory factors MCP-1, MIF, NF-κBp65, TGF-β1 and proteases MMP-1 and MMP-9 are involved in the regulation of carotid atherosclerosis. Shuangjiang Decoction and atorvastatin can effectively reduce carotid plaque area and significantly improve carotid plaque. Patients with TCM syndromes, the combination of the two is more effective, and its mechanism may be related to lowering serum MCP-1, MIF, MMP-1, MMP-9, NF-κBp65 levels and increasing serum TGF1 levels.
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Key words:
- Shuangjiang Decoction /
- carotid atherosclerotic plaque /
- MCP-1 /
- clinical study
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[1] 杜起军,崔立刚.超声诊断临床备忘录[M].北京:人民军医出版社,2012:416-417. [2] 中药新药临床研究指导原则[M].北京:中国医药科技出版社.2002:85-89. [3] 王秋风.颈动脉粥样硬化中医证候特点及其与生存质量相关性评价[D].北京:中国中医科学院,2010. [4] 陈主初.病理生理学(8年制)[M].北京:人民卫生出版社,2005:289-293. [5] HANSSEN NMJ, WOUTERS K, HUIJBERTS MS, et al. Higher levels of advanced glycation endproducts in human carotid atherosclerotic plaques are associated with a rupture-prone phenotype[J]. Eur Heart J, 2014,35(17):1137-1146. [6] RAO VH, KANSAL V, STOUPA S. MCP-1 and MMP-9 regulate epidermal growth factor dependent collagen loss in human carotid plaque smooth muscle cells[J]. Physiol Rep, 2014, 2(2): e00224. [7] 〖JP2〗MARTINVENTURA JL, BLANCOCOLIO LM, MUNOZGARCI AB, et al.〖JP〗NF-κB activation and fas ligand overexpression in blood and plaques of patients with carotid atherosclerosis: Potential implication in plaque instability[J]. Stroke, 2004, 35: 458-463. [8] CIPOLLONE F, FAZIA M, MINCIONE G,et al. Increased expression of transforming growth factor-β1 as a stabilizing factor in human atherosclerotic plaques[J]. Stroke, 2004,35: 2253-2257. [9] 巢元方.诸病源候论[M].北京:中国医药科技出版社,2011:117. [10] 朱丹溪.丹溪心法[M].北京:中国中医药出版社,2008:62. [11] 张树生. 神农本草经理论与实践[M].北京:人民卫生出版社2009:439. [12] 严洁,施雯,洪炜.得配本草[M].上海:上海科技出版社,1958:237. [13] 严金川.脆性斑块的基础与临床[M].北京:人民卫生出版社,2015:40. [14] ZHANG WJ,HUFNAGL P,BINDER BR, et al. Antiinflammatory activity of astragaloside Ⅳ is mediated by inhibition of NF-kappaB activation and adhesion molecule expression[J]. Thromb Haemostasis,2003,90(5): 904-914. [15] 刘全亮,杨中林.不同纯度山楂叶总黄酮降血脂作用的比较研究[J].海峡药学,2008,20(2):23-25. [16] 张春海,毛缜,马丽,等.泽泻水提取物、醇提取物对小鼠脂代谢影响的比较[J].徐州师范大学学报(自然科学版),2005,23(2):68-70. [17] 潘贺,刚宏林,苏云明.中药水蛭的活性成分及药理作用研究概况[J].中医药信息,2006,23(11):20-22. [18] 高兵.丹参的药理作用及临床应用分析[J].中国现代药物应用,2018,12(1):196-197. [19] 朱良春. 朱良春虫类药的应用[M].北京:人民卫生出版社,2011:187-192.
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