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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
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| 篇名： | 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 |
| TITLE： | Improvement effect and mechanism of Shengmai powder on heart failure mice with qi-yin deficiency |
| 摘要： | 目的 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、10.44g/kg（以生药量计）]以及阳性对照组（美托洛尔，30mg/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-2mRNA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、BaxmRNA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。 |
| ABSTRACT： | OBJECTIVE To study the improvement effect and mechanism of Shengmai powder on heart failure （HF） mice with qi-yin deficiency. METHODS 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 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 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. |
| 期刊： | 2025年第36卷第17期 |
| 作者： | 康兰芳；李建；赵雅婷；陈迎春；陈贵银；聂晓博；刘姣；程杰 |
| AUTHORS： | KANG Lanfang，LI Jian，ZHAO Yating，CHEN Yingchun，CHEN Guiyin，NIE Xiaobo，LIU Jiao，CHENG Jie |
| 关键字： | 生脉散；气阴两虚；心力衰竭；雷尼丁受体2；受磷蛋白；肌质网 |
| KEYWORDS： | Shengmai powder； qi-yin deficiency； heart failure； ryanodine receptor 2； phospholamban； sarcoplasmic reticulum |
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