注射用丹参多酚酸联合双联抗血小板药物对CYP2C19基因变异的颈动脉支架术后患者的治疗作用研究
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摘要
目的分析注射用丹参多酚酸联合双联抗血小板药物对CYP2C19基因变异的颈动脉支架植入术后患者的治疗作用。方法选取河南大学第一附属医院2014年1月—2017年8月96例CYP2C19基因突变且植入颈动脉支架的患者为研究对象,抽签随机分为丹参多酚组与对照组,每组48例。对照组患者术后接受双联抗血小板(阿司匹林100 mg qd+氯吡格雷75mg qd)+降脂(阿托伐他汀钙片20 mg qn)治疗,丹参多酚组除上述治疗外,术前iv注射用丹参多酚酸0.13 g,术后每日1次,每次0.13 g,共应用14 d。观察两组治疗前及治疗后超敏C反应蛋白(hs-CRP)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、内皮素-1(ET-1)、丙二醛(MDA)、一氧化氮(NO)、超氧化物歧化酶(SOD)、亲环素A(CyPA)、8异前列腺素F2α(8-iso-PGF2α)水平。术后随访1年,记录主要负性临床事件。结果治疗前两组上述指标无统计学差异;治疗后两组NO、SOD高于治疗前,hs-CRP、IL-6、TNF-α、ET-1、MDA、CyPA、8-iso-PGF2α均低于治疗前,同组治疗前后比较差异有统计学意义(P<0.05);且治疗后丹参多酚组NO、SOD高于对照组,hs-CRP、IL-6、TNF-α、ET-1、MDA、CyPA、8-iso-PGF2α低于对照组,组间差异有统计学意义(P<0.05)。丹参多酚组随访期间主要负性临床事件显著低于对照组,差异有统计学意义(P<0.05)。结论注射用丹参多酚酸联合双联抗血小板治疗能够为CYP2C19基因变异的颈动脉狭窄患者在颈动脉支架植入术后提供更好的内皮功能改善,更大程度地缓解炎症及氧化应激状态,降低主要负性临床事件发生风险。
Objective To analyze the therapeutic effect of Salvianolic Acids for Injection combined with dual antiplatelet therapy on patients with CYP2 C19 gene mutation after percutaneous carotid artery stenting. Methods A total of 96 cases with mutational CYP2 C19 genotypes treated with percutaneous carotid artery stenting in our hospital from January 2014 to August 2017 were enrolled into our study,they were randomly divided into the salvianolate group and the control group, with 48 cases in each group.The level of hs-CRP, IL-6, TNF-α, ET-1, MDA, NO, SOD, CyPA, 8-iso-PGF2α were observed before and after treatment in the two groups. The major adverse clinical events were recorded during the 1-year follow-up period. Results There was no statistical difference between the two groups before treatment. After treatment, level of NO and SOD were higher in both groups than pretreatment, while level of hs-CRP, IL-6, TNF-α, ET-1, CyPA, 8-iso-PGF2α and MDA were lower in both groups than pre-treatment(P < 0.05). Level of NO and SOD were higher in the salvianolate group than in the control group, while level of hs-CRP, IL-6, TNF-α, ET-1, CyPA, 8-iso-PGF2α and MDA were lower in the salvianolate group than in the control group(P < 0.05). The major adverse clinical events were significantly higher in the salvianolate group than in the control group(P = 0.028). Conclusion Salvianolic Acids for Injection combined with dual antiplatelet therapy can provide better endothelial function improvement in patients with CYP2 C19 gene mutation after percutaneous carotid artery stenting, and relieve inflammation and oxidative stress better as well,reduce the risk of major adverse clinical events
Objective To analyze the therapeutic effect of Salvianolic Acids for Injection combined with dual antiplatelet therapy on patients with CYP2 C19 gene mutation after percutaneous carotid artery stenting. Methods A total of 96 cases with mutational CYP2 C19 genotypes treated with percutaneous carotid artery stenting in our hospital from January 2014 to August 2017 were enrolled into our study,they were randomly divided into the salvianolate group and the control group, with 48 cases in each group.The level of hs-CRP, IL-6, TNF-α, ET-1, MDA, NO, SOD, CyPA, 8-iso-PGF2α were observed before and after treatment in the two groups. The major adverse clinical events were recorded during the 1-year follow-up period. Results There was no statistical difference between the two groups before treatment. After treatment, level of NO and SOD were higher in both groups than pretreatment, while level of hs-CRP, IL-6, TNF-α, ET-1, CyPA, 8-iso-PGF2α and MDA were lower in both groups than pre-treatment(P < 0.05). Level of NO and SOD were higher in the salvianolate group than in the control group, while level of hs-CRP, IL-6, TNF-α, ET-1, CyPA, 8-iso-PGF2α and MDA were lower in the salvianolate group than in the control group(P < 0.05). The major adverse clinical events were significantly higher in the salvianolate group than in the control group(P = 0.028). Conclusion Salvianolic Acids for Injection combined with dual antiplatelet therapy can provide better endothelial function improvement in patients with CYP2 C19 gene mutation after percutaneous carotid artery stenting, and relieve inflammation and oxidative stress better as well,reduce the risk of major adverse clinical events
引文
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[2]Meng C,Zhuo X Q,Xu G H,et al.Protection of salvianolate against atherosclerosis via regulating the inflammation in rats[J].J Huazhong Univ Sci Technolog Med Sci,2014,34(5):646-651.
[3]张建平,李志强,贺显君,等.CYP2C19基因多态性与氯吡格雷治疗缺血性脑卒中复发风险的相关性研究[J].中华实用诊断与治疗杂志,2018,32(2):152-154.
[4]Pop B,Niculae A?,Pop T L,et al.Individuals with autism have higher 8-Iso-PGF2αlevels than controls,but no correlation with quantitative assay of Paraoxonase 1serum levels[J].Metab Brain Dis,2017,32(6):1943-1950.
[5]Xue C,Sowden M,Berk B C.Extracellular cyclophilin A,especially acetylated,causes pulmonary hypertension by stimulating endothelial apoptosis,redox stress,and inflammation[J].Arterioscler Thromb Vasc Biol,2017,37(6):1138-1146.
[6]董靖德,靳凌,张丽.CYP2C19基因多态性对颈动脉支架植入术后支架内血栓形成的影响[J].实用老年医学,2016,30(8):676-678,682.
[7]刘建,山峰,徐惠霞.CYP2C19基因多态性与急性缺血性脑血管病的关系[J].青岛大学医学院学报,2017,53(04):444-446,450.
[8]王雨华,周学谦,李德坤,等.丹参多酚酸类分析方法及制备工艺的研究进展[J].药物评价研究,2017,40(7):1013-1018.
[9]Chen X,Guo Y,Hu Y,et al.Quantitative analysis of highly similar salvianolic acids with1H qNMR for quality control of traditional Chinese medicinal preparation Salvianolate Lyophilized Injection[J].JPharm Biomed Anal,2016,124:281-287.
[10]田介峰,阎红,王瑞静,等.丹参多酚酸提取物化学成分的分离与鉴定[J].中草药,2018,49(21):5024-5028.
[10]Wang J,Xiong X,Feng B.Cardiovascular effects of Salvianolic acid B[J].Evid-Based Complement Altern Med,2013,2013:1-16.
[11]王书青,邱明科,代玉鑫,等.丹参多酚盐对动脉内膜增生的影响及其机制研究[J].中国循证心血管医学杂志,2016,8(6):749-752.
[12]Wang F J,Wang S X,Chai L J,et al.Xueshuantong injection(lyophilized)combined with salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress[J].Acta Pharmacol Sin,2018,39(6):998-1011.
[13]Zhang J,Lu W,Lei Q,et al.Salvianolate increases heat shock protein expression in a cerebral ischemiareperfusion injury model[J].Neural Regen Res,2013,8(25):2327-2335.
[14]李富强,王伟,尹金鹏,等.大鼠脑缺血再灌注后线粒体ATP酶活性、形态学变化及丹参多酚酸的保护作用[J].中风与神经疾病杂志,2018,35(3):238-241.
[15]Wang F,He Q,Wang J,et al.Neuroprotective effect of salvianolate lyophilized injection against cerebral ischemia in type 1 diabetic rats[J].BMC Complement Altern Med,2017,17(1):258.
[16]He Q,Wang S,Liu X,et al.Salvianolate lyophilized injection promotes post-stroke functional recovery via the activation of VEGF and BDNF-TrkB-CREB signaling pathway[J].Int J Clin Exp Med,2015,8(1):108-22.
[17]张建娥.丹参多酚酸对合并2型糖尿病脑梗死患者抗氧化能力、血管内皮功能及神经功能缺损评分的影响[J].医药论坛杂志,2018,39(5):45-47.
[18]耿诗涵,许梦习,刘晓光,等.注射用丹参多酚酸与阿司匹林联合应用对抗凝效果和出血风险的影响[J].中国药学杂志,2018,53(1):35-39.
[19]刘施,吴嘉瑞,蔺梦娟,等.基于Meta分析的注射用丹参多酚酸治疗急性脑梗死临床评价[J].中国实验方剂学杂志,2017,23(8):202-207.
[2]Meng C,Zhuo X Q,Xu G H,et al.Protection of salvianolate against atherosclerosis via regulating the inflammation in rats[J].J Huazhong Univ Sci Technolog Med Sci,2014,34(5):646-651.
[3]张建平,李志强,贺显君,等.CYP2C19基因多态性与氯吡格雷治疗缺血性脑卒中复发风险的相关性研究[J].中华实用诊断与治疗杂志,2018,32(2):152-154.
[4]Pop B,Niculae A?,Pop T L,et al.Individuals with autism have higher 8-Iso-PGF2αlevels than controls,but no correlation with quantitative assay of Paraoxonase 1serum levels[J].Metab Brain Dis,2017,32(6):1943-1950.
[5]Xue C,Sowden M,Berk B C.Extracellular cyclophilin A,especially acetylated,causes pulmonary hypertension by stimulating endothelial apoptosis,redox stress,and inflammation[J].Arterioscler Thromb Vasc Biol,2017,37(6):1138-1146.
[6]董靖德,靳凌,张丽.CYP2C19基因多态性对颈动脉支架植入术后支架内血栓形成的影响[J].实用老年医学,2016,30(8):676-678,682.
[7]刘建,山峰,徐惠霞.CYP2C19基因多态性与急性缺血性脑血管病的关系[J].青岛大学医学院学报,2017,53(04):444-446,450.
[8]王雨华,周学谦,李德坤,等.丹参多酚酸类分析方法及制备工艺的研究进展[J].药物评价研究,2017,40(7):1013-1018.
[9]Chen X,Guo Y,Hu Y,et al.Quantitative analysis of highly similar salvianolic acids with1H qNMR for quality control of traditional Chinese medicinal preparation Salvianolate Lyophilized Injection[J].JPharm Biomed Anal,2016,124:281-287.
[10]田介峰,阎红,王瑞静,等.丹参多酚酸提取物化学成分的分离与鉴定[J].中草药,2018,49(21):5024-5028.
[10]Wang J,Xiong X,Feng B.Cardiovascular effects of Salvianolic acid B[J].Evid-Based Complement Altern Med,2013,2013:1-16.
[11]王书青,邱明科,代玉鑫,等.丹参多酚盐对动脉内膜增生的影响及其机制研究[J].中国循证心血管医学杂志,2016,8(6):749-752.
[12]Wang F J,Wang S X,Chai L J,et al.Xueshuantong injection(lyophilized)combined with salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress[J].Acta Pharmacol Sin,2018,39(6):998-1011.
[13]Zhang J,Lu W,Lei Q,et al.Salvianolate increases heat shock protein expression in a cerebral ischemiareperfusion injury model[J].Neural Regen Res,2013,8(25):2327-2335.
[14]李富强,王伟,尹金鹏,等.大鼠脑缺血再灌注后线粒体ATP酶活性、形态学变化及丹参多酚酸的保护作用[J].中风与神经疾病杂志,2018,35(3):238-241.
[15]Wang F,He Q,Wang J,et al.Neuroprotective effect of salvianolate lyophilized injection against cerebral ischemia in type 1 diabetic rats[J].BMC Complement Altern Med,2017,17(1):258.
[16]He Q,Wang S,Liu X,et al.Salvianolate lyophilized injection promotes post-stroke functional recovery via the activation of VEGF and BDNF-TrkB-CREB signaling pathway[J].Int J Clin Exp Med,2015,8(1):108-22.
[17]张建娥.丹参多酚酸对合并2型糖尿病脑梗死患者抗氧化能力、血管内皮功能及神经功能缺损评分的影响[J].医药论坛杂志,2018,39(5):45-47.
[18]耿诗涵,许梦习,刘晓光,等.注射用丹参多酚酸与阿司匹林联合应用对抗凝效果和出血风险的影响[J].中国药学杂志,2018,53(1):35-39.
[19]刘施,吴嘉瑞,蔺梦娟,等.基于Meta分析的注射用丹参多酚酸治疗急性脑梗死临床评价[J].中国实验方剂学杂志,2017,23(8):202-207.