瑞舒伐他汀与阿托伐他汀对急性心肌梗死患者心肌纤维化干预的对照研究
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摘要
目的探讨不同类型、不同剂量的他汀类药物对急性心肌梗死(AMI)患者心肌纤维化干预的效果,找到更为安全可靠的AMI治疗药物。方法选取中国中医科学院望京医院2016年2月—2018年1月收治的AMI患者160例,根据随机数字表法分为4组,各40例。A组采用常规剂量阿托伐他汀(20 mg/次,1次/d),B组采用负荷剂量阿托伐他汀(40 mg/次,1次/d),C组采用常规剂量瑞舒伐他汀(10 mg/次,1次/d),D组采用负荷剂量瑞舒伐他汀(20 mg/次,1次/d)。治疗前、治疗1周、治疗4周,分别检测并比较4组患者血脂指标、炎性指标[超敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)]、心肌纤维化指标[转化生长因子β1(TGF-β1)、Ⅰ型前胶原羟基末端肽(PICP)、半乳凝素-3(Gal-3)、结缔组织生长因子(CTGF)、Ⅲ型前胶原氨基端肽(PⅢNP)及Ⅰ型胶原羟基末端肽(ⅠCTP)],同时观察安全性。结果治疗前,4组患者血脂指标、炎性指标、心肌纤维化指标水平比较,差异均无统计学意义;治疗1、4周后,4组患者血脂指标、炎性指标均改善,且D组改善最为显著,与其他3组比较,差异有统计学意义(P<0.05);治疗1周,4组患者心肌纤维化指标水平均升高,且A组升高最为显著(P<0.05);治疗4周后,4组患者各心肌纤维化指标水平均较治疗1周有降低,但D组降低幅度最为显著,后依次为C组、B组、A组,组间比较差异有统计学意义(P<0.05)。全部患者在治疗期间均未发生明显不良反应。结论瑞舒伐他汀对AMI患者血脂、炎性反应、心肌纤维化的影响较阿托伐他汀更佳,在为患者加大负荷剂量后,心肌纤维化改善效果提升,药物毒副反应未增加,故在AMI耐受的条件下可为其使用大剂量瑞舒伐他汀治疗。
Objective To investigate the effects of different types and doses of statins in the intervention of myocardial fibrosis in patients with acute myocardial infarction(AMI), and to find more safe and reliable drugs for AMI.Methods 160 AMI patients in the hospital from February 2016 to January 2018 were selected, and they were divided into four group by random number table, with 40 cases in each group. A group: routine dose of atorvastatin(20 mg, once a day), B group: loading dose of atorvastatin(40 mg, once a day), C group: routine dose of rosuvastatin(10 mg, once a day), D group: loading dose of rosuvastatin(20 mg, once a day). The blood lipid indexes [total cholesterol(TC), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDLC)], inflammatory indexes [hypersensitive C reactive protein(hs-CRP), interleukin-6(IL-6)], myocardial fibrosis indexes[transforming growth factor-β1(TGF-β1), procollagen Ⅰ C-terminal peptide(P Ⅰ CP), galectin-3(Gal-3), connective tissue growth factor(CTGF), type III procollagen amino terminal peptide(P Ⅲ NP), type I collagen hydroxy terminal peptide( Ⅰ CTP)] in four groups before treatment, after treatment for 1 w and 4 w were compared. The safety of four groups were observed. Results Before treatment, there was no statistical difference in the blood lipid indexes, inflammatory indexes and myocardial fibrosis indexes among the four groups. After treatment for 1 w and 4 weeks, the blood lipid indexes and inflammatory indexes in four groups improved, and D group improved more significantly compared with other three groups(P < 0.05). After treatment for 1 w, the levels of myocardial fibrosis indexes in four groups increased, and A group increased more significantly; After treatment for 4 w, the levels of myocardial fibrosis indexes in four groups decreased compared with those after treatment for 1 w, but the decreased range of D group was the most significant, followed by C group, B group and A group(P < 0.05). There were no obvious adverse reactions during treatment.Conclusion Rosuvastatin has better influence on blood lipid, inflammatory response, myocardial fibrosis of AMI patients than atorvastatin. After the application of loading dose, it can improve myocardial fibrosis and not add toxic-side reactions. Therefore,large dose of rosuvastatin can be used for the treatment of AMI under the patients' tolerance.
Objective To investigate the effects of different types and doses of statins in the intervention of myocardial fibrosis in patients with acute myocardial infarction(AMI), and to find more safe and reliable drugs for AMI.Methods 160 AMI patients in the hospital from February 2016 to January 2018 were selected, and they were divided into four group by random number table, with 40 cases in each group. A group: routine dose of atorvastatin(20 mg, once a day), B group: loading dose of atorvastatin(40 mg, once a day), C group: routine dose of rosuvastatin(10 mg, once a day), D group: loading dose of rosuvastatin(20 mg, once a day). The blood lipid indexes [total cholesterol(TC), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDLC)], inflammatory indexes [hypersensitive C reactive protein(hs-CRP), interleukin-6(IL-6)], myocardial fibrosis indexes[transforming growth factor-β1(TGF-β1), procollagen Ⅰ C-terminal peptide(P Ⅰ CP), galectin-3(Gal-3), connective tissue growth factor(CTGF), type III procollagen amino terminal peptide(P Ⅲ NP), type I collagen hydroxy terminal peptide( Ⅰ CTP)] in four groups before treatment, after treatment for 1 w and 4 w were compared. The safety of four groups were observed. Results Before treatment, there was no statistical difference in the blood lipid indexes, inflammatory indexes and myocardial fibrosis indexes among the four groups. After treatment for 1 w and 4 weeks, the blood lipid indexes and inflammatory indexes in four groups improved, and D group improved more significantly compared with other three groups(P < 0.05). After treatment for 1 w, the levels of myocardial fibrosis indexes in four groups increased, and A group increased more significantly; After treatment for 4 w, the levels of myocardial fibrosis indexes in four groups decreased compared with those after treatment for 1 w, but the decreased range of D group was the most significant, followed by C group, B group and A group(P < 0.05). There were no obvious adverse reactions during treatment.Conclusion Rosuvastatin has better influence on blood lipid, inflammatory response, myocardial fibrosis of AMI patients than atorvastatin. After the application of loading dose, it can improve myocardial fibrosis and not add toxic-side reactions. Therefore,large dose of rosuvastatin can be used for the treatment of AMI under the patients' tolerance.
引文
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[3] Wang X, Lv H, Gu Y W, et al. Protective effect of lycopene on cardiac function andmyocardial fibrosis after acute myocardial infarction in rats via the modulation of p38 and MMP-9[J]. J Mol Histol, 2014, 45(1):113-120.
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[7] Yousefi K, Fathiazad F, Soraya H, et al. Marrubium vulgare L. methanolic extract inhibits inflammatory response and prevents cardiomyocyte fibrosis in isoproterenol-induced acute myocardial infarction in rats[J]. Bio Impacts, 2014, 4(1):21-27.
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[10]郝东云,刘晓明,赵静,等.不同剂量他汀类药物对急性心肌梗死早期治疗效果的影响[J].医学综述, 2015, 21(1):129-131.
[11]刘文民,陈国藩,菅颖,等.长期应用他汀类药物对急性心肌梗死PCI术中慢血流或无复流现象的影响[J].医学研究杂志, 2014, 43(6):104-107.
[12] Qu Z, Xu H X, Tian Y H, et al. Atorvastatin improves microenvironment to enhance the beneficial effects of BMSCs therapy in a rabbit model of acutemyocardial infarction[J]. Cell Physiol Biochem, 2013, 32(2):380-389.
[13] Hu X Y, Sun A J, Xie X X, et al. Rosuvastatin changes cytokine expressions in ischemic territory and preserves heart function after acutemyocardial infarction in rats[J].J Cardiovasc Pharm T, 2013, 18(2):162-176.
[14]梁玉莲,李传松,蒋跃绒.冠心病患者血清转化生长因子β1与肝细胞生长因子水平变化及其临床意义[J].中国临床保健杂志, 2017, 20(2):149-152.
[15]于鑫,刘斌,王娟娟,等.左卡尼汀对急性心肌梗死大鼠TNF-α,TGF-β1,NF-κB表达的影响[J].中国急救复苏与灾害医学杂志, 2016, 11(6):566-568.
[16]张汉平,蔡晓庆,马凌.脂肪间充质干细胞移植治疗兔急性心肌梗死的实验[J].国际心血管病杂志, 2015, 42(6):407-411.
[17]李兆欣,刘江月,李静静,等.不同剂量瑞舒伐他汀治疗对急性心肌梗死患者心肌纤维化及心室重构的影响[J].中国循证心血管医学杂志, 2016, 8(1):46-50.
[18] Velloso C P, Aperghis M, Godfrey R, et al. The effects of two weeks of recombinant growth hormone administration on the response of IGF-I and N-terminal pro-peptide of collagen type III(P-III-NP)during a single bout of high resistance exercise in resistance trained young men[J]. Growth Horm IGF Res, 2013, 23(3):76-80.
[19] Shyu K G, Wang B W, Cheng W P, et al. MicroRNA-208a Increases myocardial endoglin expression and myocardial fibrosis in acute myocardial infarction[J].Can J Cardiol, 2015, 31(5):679-690.
[20]刘亮,戴海鹰,赵扬程,等.急性心肌梗死患者血清半乳凝素-3水平变化及其相关性研究[J].中国医师杂志,2015, 17(5):729-731.
[2] Gao Q J, Yang B, Guo Y, et al. Efficacy of adenosine in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention:A PRISMAcompliant Meta-analysis[J]. Medicine, 2015, 94(32):e1279.
[3] Wang X, Lv H, Gu Y W, et al. Protective effect of lycopene on cardiac function andmyocardial fibrosis after acute myocardial infarction in rats via the modulation of p38 and MMP-9[J]. J Mol Histol, 2014, 45(1):113-120.
[4] Lewinter C, Bland J M, Crouch S, et al. Impact of aspirin and statins on long-term survival in patients hospitalized with acute myocardial infarction complicated by heart failure:an analysis of 1706 patients[J]. Eur J Heart Failure, 2014, 16(1):95-102.
[5] Macchia A, Romero M, D'Ettorre A S, et al. Exploratory analysis on the use of statins with or without n-3 PUFA and major events in patients discharged for acutemyocardial infarction:an observational retrospective study[J]. PLoS One, 2013, 8(5):e62772.
[6]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.急性ST段抬高型心肌梗死诊断和治疗指南[J].中华心血管病杂志, 2010, 38(8):675-690.
[7] Yousefi K, Fathiazad F, Soraya H, et al. Marrubium vulgare L. methanolic extract inhibits inflammatory response and prevents cardiomyocyte fibrosis in isoproterenol-induced acute myocardial infarction in rats[J]. Bio Impacts, 2014, 4(1):21-27.
[8] Yamazaki T, Nakamura Y, Shiota M, et al. Tolvaptan attenuates left ventricular fibrosis afteracute myocardial infarction in rats[J]. J Pharmacol Sci, 2013, 123(1):58-66.
[9]金晓萍,张俊杰.他汀类药物对早发冠心病急性心肌梗死患者心脏及血管内皮功能改善研究[J].北华大学学报(自然科学版), 2017, 18(5):630-632.
[10]郝东云,刘晓明,赵静,等.不同剂量他汀类药物对急性心肌梗死早期治疗效果的影响[J].医学综述, 2015, 21(1):129-131.
[11]刘文民,陈国藩,菅颖,等.长期应用他汀类药物对急性心肌梗死PCI术中慢血流或无复流现象的影响[J].医学研究杂志, 2014, 43(6):104-107.
[12] Qu Z, Xu H X, Tian Y H, et al. Atorvastatin improves microenvironment to enhance the beneficial effects of BMSCs therapy in a rabbit model of acutemyocardial infarction[J]. Cell Physiol Biochem, 2013, 32(2):380-389.
[13] Hu X Y, Sun A J, Xie X X, et al. Rosuvastatin changes cytokine expressions in ischemic territory and preserves heart function after acutemyocardial infarction in rats[J].J Cardiovasc Pharm T, 2013, 18(2):162-176.
[14]梁玉莲,李传松,蒋跃绒.冠心病患者血清转化生长因子β1与肝细胞生长因子水平变化及其临床意义[J].中国临床保健杂志, 2017, 20(2):149-152.
[15]于鑫,刘斌,王娟娟,等.左卡尼汀对急性心肌梗死大鼠TNF-α,TGF-β1,NF-κB表达的影响[J].中国急救复苏与灾害医学杂志, 2016, 11(6):566-568.
[16]张汉平,蔡晓庆,马凌.脂肪间充质干细胞移植治疗兔急性心肌梗死的实验[J].国际心血管病杂志, 2015, 42(6):407-411.
[17]李兆欣,刘江月,李静静,等.不同剂量瑞舒伐他汀治疗对急性心肌梗死患者心肌纤维化及心室重构的影响[J].中国循证心血管医学杂志, 2016, 8(1):46-50.
[18] Velloso C P, Aperghis M, Godfrey R, et al. The effects of two weeks of recombinant growth hormone administration on the response of IGF-I and N-terminal pro-peptide of collagen type III(P-III-NP)during a single bout of high resistance exercise in resistance trained young men[J]. Growth Horm IGF Res, 2013, 23(3):76-80.
[19] Shyu K G, Wang B W, Cheng W P, et al. MicroRNA-208a Increases myocardial endoglin expression and myocardial fibrosis in acute myocardial infarction[J].Can J Cardiol, 2015, 31(5):679-690.
[20]刘亮,戴海鹰,赵扬程,等.急性心肌梗死患者血清半乳凝素-3水平变化及其相关性研究[J].中国医师杂志,2015, 17(5):729-731.