
浏览全部资源
扫码关注微信
1.河北省中医院药学部,石家庄 050011
2.河北省中医药管理局中药评价及转化重点研究室,石家庄 050011
3.北京同仁堂制药有限公司, 北京 102629
4.石家庄医学高等专科学校药学系,石家庄 050062
5.河北中医药大学药学院,石家庄 050200
主管中药师。研究方向:中药药效研究及安全性评价。E-mail:1250031701@qq.com
副教授,硕士。研究方向:中药药效物质及药理机制。E-mail:251482424@qq.com
收稿日期:2025-04-12,
修回日期:2025-08-03,
录用日期:2025-08-04,
纸质出版日期:2025-09-15
移动端阅览
康兰芳,李建,赵雅婷,等.生脉散对气阴两虚型心力衰竭小鼠的改善作用及机制研究 [J].中国药房,2025,36(17):2127-2133.
KANG Lanfang,LI Jian,ZHAO Yating,et al.Improvement effect and mechanism of Shengmai powder on heart failure mice with qi-yin deficiency[J].ZHONGGUO YAOFANG,2025,36(17):2127-2133.
康兰芳,李建,赵雅婷,等.生脉散对气阴两虚型心力衰竭小鼠的改善作用及机制研究 [J].中国药房,2025,36(17):2127-2133. DOI: 10.6039/j.issn.1001-0408.2025.17.08.
KANG Lanfang,LI Jian,ZHAO Yating,et al.Improvement effect and mechanism of Shengmai powder on heart failure mice with qi-yin deficiency[J].ZHONGGUO YAOFANG,2025,36(17):2127-2133. DOI: 10.6039/j.issn.1001-0408.2025.17.08.
目的
2
研究生脉散对气阴两虚型心力衰竭(HF)小鼠的改善作用及机制。
方法
2
将小鼠随机分为空白组(水)、模型组(水)和生脉散低、中、高剂量组[2.61、5.22、10.44 g/kg(以生药量计)]以及阳性对照组(美托洛尔,30 mg/kg),每组10只。除空白组外,其余各组小鼠通过皮下注射D-半乳糖,并持续限食与负重游泳来建立气阴两虚型HF模型。造模同时,灌胃相应药液/水,每天1次,连续5周。记录小鼠一般状态并进行中医证候评分;通过行为学实验考察小鼠旷场行动总距离、木僵时间百分比、游泳力竭时间;检测小鼠心功能相关指标[心率、左心室射血分数(LVEF)、左心室收缩末内径(LVESD)、左心室舒张末内径(LVEDD)、左心室质量指数和全心质量指数];检测小鼠血清中天冬氨酸转氨酶(AST)、肌酸激酶(CK)、乳酸脱氢酶(LDH)含量;观察小鼠心肌组织病理学形态;检测小鼠心肌细胞凋亡水平;检测小鼠心肌组织中B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)、剪切型胱天蛋白酶3(Cleaved-caspase-3)的mRNA表达水平;检测小鼠心肌组织中肌质网钙调控相关蛋白[雷诺丁受体2(RyR2)、受磷蛋白(PLB)]的磷酸化水平。
结果
2
与空白组比较,模型组小鼠的体重、旷场行动总距离、游泳力竭时间、LVEF、LVEDD以及心肌组织中Bcl-2 mRNA表达水平和PLB蛋白磷酸化水平均显著降低/缩短(
P
<0.05);中医证候评分、木僵时间百分比、心率、LVESD、左心室质量指数、全心质量指数、心肌细胞凋亡率,血清中CK、LDH、AST含量,心肌组织中Cleaved-caspase-3、Bax mRNA表达水平以及RyR2蛋白磷酸化水平均显著升高(
P
<0.05);心肌组织存在炎症细胞浸润,细胞排列紊乱且心肌间质纤维化明显。经生脉散干预后,小鼠上述大部分定量指标均显著逆转(
P
<0.05),心肌组织炎症细胞浸润减少,纤维化程度明显减轻。
结论
2
生脉散可改善气阴两虚型HF小鼠心功能,降低心肌细胞凋亡水平和心肌纤维化程度,其作用机制可能与调节肌质网钙调控相关蛋白表达有关。
OBJECTIVE
2
To study the improvement effect and mechanism of Shengmai powder on heart failure (HF) mice with qi-yin deficiency.
METHODS
2
The mice were randomly divided into blank group (water), model group (water), Shengmai powder low-, medium-, and high-dose groups [2.61, 5.22 and 10.44 g/kg (based on crude drug dosage)] and positive control group (metoprolol, 30 mg/kg), with 10 mice in each group. Except for the blank group, all other groups were subcutaneously injected with D-galactose, and a qi-yin deficiency HF mice model was established by continuous food restriction and weight-bearing swimming. At the same time of modeling, the corresponding medicine/water was gavaged once a day for five weeks. The general state of mice was recorded and the traditional Chinese medicine (TCM) syndrome score was evaluated. Behavioral experiments were conducted to investigate the total distance of open field action, the percentage of immobility time, and the swimming exhaustion time of mice. The contents of aspartate transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) in the serum of mice were detected; cardiac function indexes [heart rate, left ventricular ejection fraction (LVEF), left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular mass index and whole heart mass index] were all detected; the histopathological morphology of mice myocardium was observed; the level of cardiomyocyte apoptosis in mice was detected; mRNA expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), and Cleaved-caspase-3 in myocardial tissue of mice were detected; the phosphorylation levels of sarcoplasmic reticulum calcium regulatory related proteins [ryanodine receptor 2 (RyR2) and phospholamban (PLB)] in myocardial tissue of mice were detected.
RESULTS
2
Compared with the blank group, the body weight, total distance of open field action, swimming exhaustion time, LVEF, LVEDD, Bcl-2 mRNA expression level in myocardial tissue and PLB protein phosphorylation level in the model group were significantly reduced/shortened (
P
<0.05); TCM syndrome score, the percentage of immobility time, heart rate, LVESD, left ventricular mass index, whole heart mass index, cardiomyocyte apoptosis rate, the contents of CK, LDH and AST in serum, mRNA expression levels of Cleaved-caspase-3 and Bax and the phosphorylation level of RyR2 protein in myocardial tissue were significantly increased (
P
<0.05); there were inflammatory cell infiltration, disordered cell arrangement and obvious myocardial interstitial fibrosis in myocardial tissue. After the intervention of Shengmai powder, most of the above quantitative indexes in mice were significantly reversed (
P
<0.05), the inflammatory cell infiltration in myocardial tissue was reduced, and the degree of fibrosis was significantly reduced.
CONCLUSIONS
2
Shengmai powder can improve cardiac function, reduce the level of cardiomyocyte apoptosis and myocardial fibrosis in HF mice with qi-yin deficiency. Its mechanism may be related to the regulation of the expression of sarcoplasmic reticulum calcium regulation related proteins.
柴坷 , 杨杰孚 . 心力衰竭诊断和治疗的现状和思考 [J ] . 心脑血管病防治 , 2020 , 20 ( 1 ): 10 - 12,24 .
VAN DER MEER P , GAGGIN H K , DEC G W . ACC/AHA versus ESC guidelines on heart failure:JACC guideline comparison [J ] . J Am Coll Cardiol , 2019 , 73 ( 21 ): 2756 - 2768 .
WANG H , CHAI K , DU M H , et al . Prevalence and incidence of heart failure among urban patients in China:a national population-based analysis [J ] . Circ Heart Fail , 2021 , 14 ( 10 ): e008406 .
ROTH G A , FOROUZANFAR M H , MORAN A E , et al . Demographic and epidemiologic drivers of global cardiovascular mortality [J ] . N Engl J Med , 2015 , 372 ( 14 ): 1333 - 1341 .
ROSENBERG P . VDAC2 as a novel target for heart fai- lure:Ca 2+ at the sarcomere,mitochondria and SR [J ] . Cell Calcium , 2022 , 104 : 102586 .
LANDSTROM A P , DOBREV D , WEHRENS X H T . Calcium signaling and cardiac arrhythmias [J ] . Circ Res , 2017 , 120 ( 12 ): 1969 - 1993 .
DEL RE D P , AMGALAN D , LINKERMANN A , et al . Fundamental mechanisms of regulated cell death and implications for heart disease [J ] . Physiol Rev , 2019 , 99 ( 4 ): 1765 - 1817 .
张松 , 廖宪勇 , 李白雪 . 中医治疗慢性心力衰竭的证候分析 [J ] . 四川中医 , 2020 , 38 ( 2 ): 208 - 211 .
杨月东 , 汪茂林 , 赵娟 , 等 . 基于CMR评价生脉散颗粒抑制慢性心力衰竭气阴两虚证患者心肌纤维化的临床疗效 [J ] . 中国实验方剂学杂志 , 2023 , 29 ( 23 ): 89 - 97 .
张忠 , 李雅姝 , 胡庆汐 , 等 . 生脉散调控钙稳态影响心肌细胞收缩的机制研究 [J ] . 河北中医药学报 , 2025 , 40 ( 4 ): 78 - 81 .
黄聪 , 孙明杰 , 崔海峰 , 等 . 基于网络药理学探讨生脉散降低钙泄漏保护糖尿病大鼠心肌收缩功能的机制研究 [J ] . 药学学报 , 2022 , 57 ( 10 ): 3115 - 3123 .
王柏惠 , 王经 , 王琦 , 等 . D-半乳糖致心脏衰老动物模型的建立及评估 [J ] . 华中科技大学学报(医学版) , 2025 , 54 ( 2 ): 211 - 216 .
李宗源 , 郝莉雨 , 孙建辉 , 等 . 3种气虚证动物模型的比较与评价 [J ] . 中医杂志 , 2022 , 63 ( 18 ): 1773 - 1778 .
毛静远 , 朱明军 . 慢性心力衰竭中医诊疗专家共识 [J ] . 中医杂志 , 2014 , 55 ( 14 ): 1258 - 1260 .
郑筱萸 . 中药新药临床研究指导原则:试行 [M ] . 北京 : 中国医药科技出版社 , 2002 : 352 - 353 .
鲁江斌 , 王英莉 , 杨登魁 , 等 . LVEF≤50%的急性冠状动脉综合征患者行经皮冠状动脉介入治疗前后微循环、心功能变化及预后影响因素分析 [J ] . 临床和实验医学杂志 , 2024 , 23 ( 18 ): 1920 - 1924 .
马慕秾 , 董英杰 , 雷珊珊 , 等 . 黄精不同炮制品对气阴两虚模型大鼠的药效研究 [J ] . 上海中医药杂志 , 2019 , 53 ( 10 ): 83 - 89 .
张俊彪 , 郭军霞 . 红景天苷对人心肌细胞缺氧损伤的保护作用及可能机制 [J ] . 中国现代医学杂志 , 2017 , 27 ( 8 ): 21 - 26 .
张欣欣 , 宋瑞婧 , 高飞 , 等 . 基于内质网应激GRP78/PERK/CHOP信号通路探讨益肾通络方对膜性肾病大鼠足细胞凋亡的影响 [J ] . 中药药理与临床 , 2021 , 37 ( 5 ): 102 - 109 .
何泽 , 成光宇 , 吕美香 , 等 . 解毒通络保肾法对实验性DM大鼠肾足细胞凋亡相关因子Bax、Bcl-2、Caspase-3的影响 [J ] . 中国老年学杂志 , 2019 , 39 ( 6 ): 1414 - 1417 .
WU Y , WANG M L , XU J , et al . Signature network-based survey of the effects of a traditional Chinese medicine on heart failure [J ] . J Ethnopharmacol , 2022 , 283 : 114750 .
VADUGANATHAN M , CLAGGETT B L , JHUND P S , et al . Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction:a comparative analysis of three randomised controlled trials [J ] . Lancet , 2020 , 396 ( 10244 ): 121 - 128 .
0
浏览量
13
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
公网安备50010302001817