ZHUANG Jinlong,CHEN Hua,LIU Li,et al.Effects of Shenqi Lixin Decoction on Levels of N-terminal B-type Natriuretic Peptide, Angiotension and Myocardial Fibrosis in Rats with Heart Failure[J].zhongguo zhongyiyao xinxi zazhi,2021,28(1):73-80.[doi:10.19879/j.cnki.1005-5304.202006434]
参芪利心汤对心力衰竭大鼠血浆N端B型利钠肽原、血管紧张素Ⅱ水平及心肌纤维化的影响
- Title:
- Effects of Shenqi Lixin Decoction on Levels of N-terminal B-type Natriuretic Peptide, Angiotension and Myocardial Fibrosis in Rats with Heart Failure
- 文章编号:
- 1005-5304(2021)01-0073-08
- 分类号:
- R285.5
- 文献标志码:
- A
- 摘要:
- 目的 观察参芪利心汤对心力衰竭大鼠心功能、血浆N端B型利钠肽原（NT-proBNP）、血管紧张素Ⅱ（AngⅡ）水平及心肌纤维化的影响，初步探讨其干预心力衰竭的作用机制。方法 将105只Wistar雄性大鼠随机分为空白对照组、模型组、依那普利组和参芪利心汤低、中、高剂量组，除空白对照组15只外，余各组均为18只。阿霉素诱导制备心力衰竭大鼠模型，造模后除对照组和模型组灌胃等体积蒸馏水外，余各组均予相应药物灌胃，连续4周。药物干预结束后，超声心动图仪检测大鼠左室收缩末期内径（LVESd）、左室舒张末期内径（LVEDd）、射血分数（EF）、短轴缩短率（FS）、心输出量（CO）；Masson染色观察心肌组织形态，并测定胶原容积分数（CVF）；ELISA测定血浆NT-proBNP、AngⅡ水平；RT-qPCR检测心肌组织Ⅰ型胶原（CollagenⅠ）、Ⅲ型胶原（Collagen Ⅲ）mRNA的表达；Western blot检测心肌组织CollagenⅠ、Collagen Ⅲ蛋白的表达。结果 与空白对照组比较，模型组大鼠LVESd、LVEDd，心肌CVF，血浆NT-proBNP及AngⅡ水平，心肌组织CollagenⅠ、Collagen Ⅲ mRNA及蛋白表达均明显升高，EF、FS、CO均明显降低，差异有统计学意义（P＜0.001）；与模型组比较，各给药组大鼠LVESd、LVEDd，心肌CVF，血浆NT-proBNP及AngⅡ水平，心肌组织CollagenⅠ、Collagen Ⅲ mRNA及蛋白表达均不同程度降低，EF、FS、CO均不同程度升高，除参芪利心汤低剂量组外，余各组差异均有统计学意义（P＜0.01，P＜0.001）。结论 参芪利心汤可明显改善心力衰竭大鼠心功能，其机制可能是通过降低血浆AngⅡ水平，减少心肌组织胶原纤维增生，下调心肌组织CollagenⅠ和Collagen Ⅲ的表达，从而抑制心肌纤维化、逆转心室重构。
- Abstract:
- Objective To observe the effect of Shenqi Lixin Decoction on cardiac function, the levels of plasma N-terminal B-type natriuretic peptide (NT-proBNP) and angiotension Ⅱ (AngⅡ), and myocardial fibrosis in doxorubicin-induced heart failure rats; To preliminarily explore the mechanism of its intervention in heart failure. Methods Totally 105 male Wistar rats were randomly divided into blank control group, model group, enalapril group, Shenqi Lixin Decoction low-, medium-, and high-dosage groups, with 18 rats in each group except 15 rats in the blank control group. Doxorubicin was used to induce heart failure rats model. After modeling, except the blank control group and the model group receiving equal volume of distilled water for gavage, other groups received gavage with relevant medicine, for 4 weeks. After the drug intervention, the left ventricular end systolic diameter ( LVESd), left ventricular end diastolic diameter (LVEDd), ejection fraction (EF), short axis shortening rate (FS) and cardiac output (CO) were measured by echocardiography; Masson staining was used to observe the myocardial morphology and determine the volume fraction of collagen (CVF); the levels of NT-proBNP and Ang Ⅱ in plasma were measured by ELISA; the mRNA expressions of collagenⅠ and collagen Ⅲ in myocardial tissue was detected by RT-qPCR; the protein expressions of collagenⅠ and collagen Ⅲ in myocardial tissue were detected by Western blot. Results Compared with the blank control group, the LVESd, LVEDd, CVF, NT-proBNP and AngⅡ levels, collagenⅠ and collagen Ⅲ mRNA and protein expression significantly increased in model group, the EF, FS and CO decreased significantly, with statistical significance (P<0.001); compared with the model group, the LVESd, LVEDd, CVF, NT-proBNP and AngⅡ levels, collagenⅠ and collagen Ⅲ mRNA and protein expression in myocardial tissue of each drug administration group decreased to different degrees, the EF, FS and CO increased in varying degrees. Except for Shenqi Lixin Decoction low-dosage group, the differences in other groups were statistically significant ( P<0.01, P<0.001). Conclusion Shenqi Lixin Decoction can improve the cardiac function of heart failure rats, and its mechanism may be through reducing the plasma AngⅡ level, decrease the proliferation of collagen fibers in myocardial tissue, down-regulate the expressions of collagenⅠ and collagen Ⅲ in myocardial tissue, so as to inhibit myocardial fibrosis and reverse ventricular remodeling.
参考文献/References:
[1] 中华医学会心血管病学分会心力衰竭学组,中国医师协会心力衰竭专业委员会.中国心力衰竭诊断和治疗指南2018[J].中华心血管病杂志, 2018,46(10)：760-789. [2] 国家卫生计生委合理用药专家委员会,中国药师协会.心力衰竭合理用药指南[J].中国医学前沿杂志(电子版),2016,8(9)：19-66. [3] 刘莉,高晶,金娟.刘莉运用参芪益心汤加减治疗慢性心力衰竭临床经验[J].中医药临床杂志,2015,27(9)：1243-1245. [4] 孙雪平,刘莉,邹国良,等.参芪益心汤加减治疗慢性心力衰竭60例临床观察[J].中医药信息,2013,30(3)：87-89. [5] 金娟,崔璐,邹国良,等.参芪益心方对阿霉素诱导的慢性心力衰竭大鼠心肌结构和细胞因子的影响[J].中国实验方剂学杂志,2014,20(8)：128-132. [6] 郭振,樊迪,刘方圆,等.阿霉素诱导的心脏毒性的研究进展[J].中华医学杂志,2020,100(1)：68-71. [7] WU S J, ZHU L Q, YANG J, et al. Hydrogen-containing saline attenuates doxorubicin-induced heart failure in rats[J]. Die Pharmazie,2014,69(8)：633-636. [8] 成忠煌,胡雪峰,彭敏,等.阿霉素诱导大鼠慢性心力衰竭模型给药剂量和频率的优化[J].湖北中医杂志,2011,33(4)：9-11. [9] 王庆涛,王玉璟.不同给药方式建立阿霉素心肌病模型的评价[J].长江大学学报：自然科学版,2017,14(12)：80-83,89. [10] PAULUS W J, TSCHÖPE C. A novel paradigm for heart failure with preserved ejection fraction：comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation[J]. J Am Coll Cardiol,2013,62(4)：263-271. [11] CAVALERA M, WANG J H, FRANGOGIANNIS N G. Obesity, metabolic dysfunction, and cardiac fibrosis：pathophysiological pathways, molecular mechanisms, and therapeutic opportunities[J]. Transl Res,2014,164(4)：323-335. [12] LBPEZ B, GONZALEZ A, RAVASSA S, et a1. Circulating biomarkers of myocardial fibrosis：The need for a reappraisal[J]. J Am Coll Cardiol,2015,65(22)：2449-2456. [13] ONGSTAD E, KOHL P. Fibroblast-myocyte coupling in the heart：Potential relevance for therapeutic interventions[J]. J Mol Cell Cardiol,2016,91：238-246. [14] 王东旭,金智生,张花治,等.红芪多糖对模型小鼠糖尿病心肌病心肌纤维化和基质金属蛋白酶2 及其抑制剂表达的影响[J].中国中医药信息杂志,2017,24(4)：57-60. [15] BOOTH R A, HILL S A, DON-WAUCHOPE A, et al. Performance of BNP and NT-proBNP for diagnosis of heart failure in primary care patients：a systematic review[J]. Heart Fail Rev,2014,19(4)：439-451. [16] ROBERTS E, LUDMAN A J, DWORZYNSKI K, et al. The diagnostic accuracy of the natriuretic peptides in heart failure：systematic review and diagnostic meta-analysis in the acute care setting[J]. BMJ,2015,350：h910. [17] BETTENCOURT P, AZEVEDO A, PIMENTA J, et al. N-terminal-pro- brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients[J]. Circulation,2004, 110(15)：2168-2174. [18] 崔红燕,彭渊,吴琦,等.丹酚酸B 盐抗腹主动脉不完全结扎大鼠心肌纤维化的实验研究[J].中国中医药信息杂志,2010,17(7)：46-48. [19] BARAUNA V G, MAGALHAES F C, KRIEGER J E, et al. AT1 receptor participates in the cardiac hypertrophy induced by resistance training in rats[J]. Am J Physiol RegulIntegr Comp Physiol,2008, 295(2)：381-387. [20] PENGH M, CARRETEROO A, VULJAJ N, et al. Angiotensin-converting enzyme inhibitors：a new mechanism of action[J]. Circulation, 2005,112(16)：2436-2445. [21] MERCER S E, ODELBERG S J, SIMON H G. A dynamic spatiotemporal extracellular matrix facilitates epicardial-mediated vertebrate heart regeneration[J]. Dev Biol,2013,382(2)：457-469. [22] TOPRAK G, YUKSEL H, DEMIRPENCE O, et al. Fibrosis in heart failure subtypes[J]. Eur Rev Med Pharmacol Sci,2013,17(17)：2302- 2309. [23] 韩振强,沈建平.慢性心力衰竭中医治疗进展[J].吉林中医药,2009, 29(10)：916-918. [24] 彭程飞,李佳,田孝祥,等.人参皂苷Rg1抑制大鼠急性心肌梗死后心肌纤维化[J].现代生物医学进展,2017,17(16)：3005-3007. [25] 唐斌,张金国,谭洪勇,等.黄芪甲苷对慢性心衰大鼠心肌纤维化及能量代谢的影响[J].中国病理生理杂志,2017,33(3)：411-416. [26] 岳星星,谢春毅.中医药防治糖尿病心肌纤维化机制研究进展[J].中国中医药信息杂志,2017,24(5)：124-128.
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备注/Memo
基金项目：国家自然科学基金青年基金（81601223）；福建中医药大学临床专项课题基金（XB2018126）
更新日期/Last Update:
2020-12-18