化瘀方抗大鼠心肌纤维化疗效及其与氧化应激的关系
|
摘要
目的探讨化瘀方对自发性高血压大鼠(SHR)心肌纤维化的疗效及其与氧化应激的关系。方法结合中医理论和网络药理学,预测化瘀方为血府逐瘀汤抗心肌纤维化有效药物组合。SHR分为模型组,化瘀方低、中、高剂量组,血府逐瘀汤组和卡托普利组,Wistar-Kyoto(WKY)大鼠作为正常对照组。超声心动图、无创尾压仪、组织病理学检测心肌纤维化程度,反转录PCR(qRT-PCR)和Western blot检测抗氧化酶的表达。结果与模型组比较,化瘀方低、中、高剂量组射血分数和短轴缩短率增加(P<0.05),血压、肌酸激酶同工酶MB(CK-MB)的表达降低(P<0.05),心肌纤维化减轻,且化瘀方高剂量疗效与血府逐瘀汤组相当。同时,与模型组比较,高剂量化瘀方能增加过氧化氢酶(CAT)、谷胱肽过氧化物酶(GPx)的表达(P<0.05)。结论化瘀方抗大鼠心肌纤维化的疗效可能与减轻氧化应激有关。
Objective To observe the efficacy of Hua-Yu decoction for myocardial fibrosis in spontaneously hypertensive rats(SHR)and its relationship with oxidative stress.Methods Based on the traditional Chinese medicine theory and network pharmacology,we predicted that Hua-Yu decoction was the main effective component of Xue-Fu-Zhu-Yu decoction on anti-hypertensive myocardial fibrosis.12-week-old male spontaneous hypertension rats(SHR)were randomized into six groups:the model group,the Hua-Yu decoction group at low-,medium-,and high-dose,the Xue-Fu-Zhu-Yu decoction group and the captopril group,WistarKyoto(WKY)rats as the model group.The cardiac fibrosis was observed using echocardiography,non-invasive tail pressure gauge and histological examination.The mRNA and protein expression of cellular defense enzymes were determined through quantitative real time poly merase chain reaction(qRT-PCR)and Western blot.Results Compared with the model group,ejection fraction and fraction shortening increased in the HuaYu decoction group at low-,medium-or high-dose(P<0.05),while blood pressure and the expression of creatine kinase-MB(CK-MB)decreased,myocardial fibrosis was inhibited.There was no significant difference between Hua-Yu decoction and Xue-Fu-Zhu-Yu decoction.Moreover,Hua-Yu decoction could increase the expression of catalase(CAT)and glutathione peroxidase(GPX,P<0.05).Conclusion Hua-Yu decoction had the effect of anti-hypertensive myocardial fibrosis,which may be related to alleviating oxidative stress.
Objective To observe the efficacy of Hua-Yu decoction for myocardial fibrosis in spontaneously hypertensive rats(SHR)and its relationship with oxidative stress.Methods Based on the traditional Chinese medicine theory and network pharmacology,we predicted that Hua-Yu decoction was the main effective component of Xue-Fu-Zhu-Yu decoction on anti-hypertensive myocardial fibrosis.12-week-old male spontaneous hypertension rats(SHR)were randomized into six groups:the model group,the Hua-Yu decoction group at low-,medium-,and high-dose,the Xue-Fu-Zhu-Yu decoction group and the captopril group,WistarKyoto(WKY)rats as the model group.The cardiac fibrosis was observed using echocardiography,non-invasive tail pressure gauge and histological examination.The mRNA and protein expression of cellular defense enzymes were determined through quantitative real time poly merase chain reaction(qRT-PCR)and Western blot.Results Compared with the model group,ejection fraction and fraction shortening increased in the HuaYu decoction group at low-,medium-or high-dose(P<0.05),while blood pressure and the expression of creatine kinase-MB(CK-MB)decreased,myocardial fibrosis was inhibited.There was no significant difference between Hua-Yu decoction and Xue-Fu-Zhu-Yu decoction.Moreover,Hua-Yu decoction could increase the expression of catalase(CAT)and glutathione peroxidase(GPX,P<0.05).Conclusion Hua-Yu decoction had the effect of anti-hypertensive myocardial fibrosis,which may be related to alleviating oxidative stress.
引文
[1]MARON M S,CHAN R H,KAPUR N,et al.Effect of spironolactone on myocardial fibrosis and other clinical variables in patients with hypertrophic cardiomyopathy:a prospective,randomized trial[J].Am J Med,2018,131(7):837-841.
[2]DONG Y,YANG D,HAN Y,et al.Age and gender impact the measurement of myocardial interstitial fibrosis in a healthy adult chinese population:a cardiac magnetic resonance study[J].Front Physiol,2018,9:140.
[3]RODRIGO R,LIBUY M,FELIU F,et al.Oxidative stressrelated biomarkers in essential hypertension and ischemiareperfusion myocardial damage[J].Dis Markers,2013,35(6):773-790.
[4]ZHANG G,YANG G,DENG Y,et al.Ameliorative effects of Xue-Fu-Zhu-Yu decoction,Tian-Ma-Gou-Teng-Yin and WenDan decoction on myocardial fibrosis in a hypertensive rat mode[J].BMC Complement Altern Med,2016,16:56.
[5]李雨庭,李诗畅,牛雯颖,等.方剂药理研究的方法与思路[J].中国实验方剂学杂志,2017,23(21):229-234.
[6]PANG X C,KANG,FANG J S,et al.Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer′s disease[J].Chin J Nat Med,2018,16(1):53-62.
[7]MUHAMMD J,KHAN A,ALI A,et al.Network pharmacology:exploring the resources and methodologies[J].Curr Top Med Chem,2018,18(12):949-964.
[8]TAO L,SHEN S,FU S,et al.Traditional chinese medication qiliqiangxin attenuates cardiac remodeling after acute myocardial infarction in mice[J].Sci Rep,2015,5:8374.
[9]ROSALKI S B,ROBERTS R,KATUS H A,et al.Cardiac biomarkers for detection of myocardial infarction:perspectives from past to present[J].Clin Chem,2004,50(11):2205-2213.
[10]HOEY E T,PAKALA V,TEOH J K,et al.The role of imaging in hypertensive heart disease[J].Int J Angiol,2014,23(2):85-92.
[11]PUDDU P,PUDDU G M,CRAVERO E,et al.The molecular sources of reactive oxygen species in hypertension[J].Blood Press,2008,17(2):70-77.
[12]SENTHIL S,VEERAPPAN R M,RAMAKRISHNA RM,et al.Oxidative stress and antioxidants in patients with cardiogenic shock complicating acute myocardial infarction[J].Clin Chim Acta,2004,348(1):131-137.
[13]WU J,HECKER J G,CHIAMVIMONVAT N.Antioxidant enzyme gene transfer for ischemic diseases[J].Adv Drug Deliv Rev,2009,61(4):351-363.
[14]CARILLON J,RUGALE C,ROUANET J M,et al.Endogenous antioxidant defense induction by melon superoxide dismutase reduces cardiac hypertrophy in spontaneously hypertensive rats[J].Int J Food Sci Nutr,2014,65(5):602-609.
[15]吕仕超,杨锡燕,张军平.中医药治疗高血压心肌纤维化的研究[J].世界科学技术-中医药现代化,2015,17(6):1295-1299.
[16]祁轶斐,任学娇,娄利霞,等.扶正化瘀胶囊对心肌梗死后心肌纤维化大鼠细胞外基质代谢的影响[J].中医杂志,2018,59(7):607-611.
[17]崔爽,吴军,鲁阳侠.益气化瘀汤对慢性心力衰竭心肌纤维化机制的影响研究[J].重庆医学,2017,46(18):2548-2551.
[18]马新欣,张跃力,王曼,等.自发性高血压大鼠左心室心肌应变与心肌纤维化程度的相关性[J].中国医学影像技术,2017,33(2):161-166.
[19]POTJE S R,TROIANO J A,GRANDO M D,et al.Endothelial modulation of a nitric oxide donor complex-induced relaxation in normotensive and spontaneously hypertensive rats[J].Life Sci,2018,201:130-140.
[20]BAKER J,KIMPINSKI K.Role of melatonin in blood pressure regulation:an adjunct anti-hypertensive agent[J].Clin Exp Pharmacol Physiol,2018,45(8):755-766.
[2]DONG Y,YANG D,HAN Y,et al.Age and gender impact the measurement of myocardial interstitial fibrosis in a healthy adult chinese population:a cardiac magnetic resonance study[J].Front Physiol,2018,9:140.
[3]RODRIGO R,LIBUY M,FELIU F,et al.Oxidative stressrelated biomarkers in essential hypertension and ischemiareperfusion myocardial damage[J].Dis Markers,2013,35(6):773-790.
[4]ZHANG G,YANG G,DENG Y,et al.Ameliorative effects of Xue-Fu-Zhu-Yu decoction,Tian-Ma-Gou-Teng-Yin and WenDan decoction on myocardial fibrosis in a hypertensive rat mode[J].BMC Complement Altern Med,2016,16:56.
[5]李雨庭,李诗畅,牛雯颖,等.方剂药理研究的方法与思路[J].中国实验方剂学杂志,2017,23(21):229-234.
[6]PANG X C,KANG,FANG J S,et al.Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer′s disease[J].Chin J Nat Med,2018,16(1):53-62.
[7]MUHAMMD J,KHAN A,ALI A,et al.Network pharmacology:exploring the resources and methodologies[J].Curr Top Med Chem,2018,18(12):949-964.
[8]TAO L,SHEN S,FU S,et al.Traditional chinese medication qiliqiangxin attenuates cardiac remodeling after acute myocardial infarction in mice[J].Sci Rep,2015,5:8374.
[9]ROSALKI S B,ROBERTS R,KATUS H A,et al.Cardiac biomarkers for detection of myocardial infarction:perspectives from past to present[J].Clin Chem,2004,50(11):2205-2213.
[10]HOEY E T,PAKALA V,TEOH J K,et al.The role of imaging in hypertensive heart disease[J].Int J Angiol,2014,23(2):85-92.
[11]PUDDU P,PUDDU G M,CRAVERO E,et al.The molecular sources of reactive oxygen species in hypertension[J].Blood Press,2008,17(2):70-77.
[12]SENTHIL S,VEERAPPAN R M,RAMAKRISHNA RM,et al.Oxidative stress and antioxidants in patients with cardiogenic shock complicating acute myocardial infarction[J].Clin Chim Acta,2004,348(1):131-137.
[13]WU J,HECKER J G,CHIAMVIMONVAT N.Antioxidant enzyme gene transfer for ischemic diseases[J].Adv Drug Deliv Rev,2009,61(4):351-363.
[14]CARILLON J,RUGALE C,ROUANET J M,et al.Endogenous antioxidant defense induction by melon superoxide dismutase reduces cardiac hypertrophy in spontaneously hypertensive rats[J].Int J Food Sci Nutr,2014,65(5):602-609.
[15]吕仕超,杨锡燕,张军平.中医药治疗高血压心肌纤维化的研究[J].世界科学技术-中医药现代化,2015,17(6):1295-1299.
[16]祁轶斐,任学娇,娄利霞,等.扶正化瘀胶囊对心肌梗死后心肌纤维化大鼠细胞外基质代谢的影响[J].中医杂志,2018,59(7):607-611.
[17]崔爽,吴军,鲁阳侠.益气化瘀汤对慢性心力衰竭心肌纤维化机制的影响研究[J].重庆医学,2017,46(18):2548-2551.
[18]马新欣,张跃力,王曼,等.自发性高血压大鼠左心室心肌应变与心肌纤维化程度的相关性[J].中国医学影像技术,2017,33(2):161-166.
[19]POTJE S R,TROIANO J A,GRANDO M D,et al.Endothelial modulation of a nitric oxide donor complex-induced relaxation in normotensive and spontaneously hypertensive rats[J].Life Sci,2018,201:130-140.
[20]BAKER J,KIMPINSKI K.Role of melatonin in blood pressure regulation:an adjunct anti-hypertensive agent[J].Clin Exp Pharmacol Physiol,2018,45(8):755-766.