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补肾活血方对心肌梗死后心力衰竭大鼠心肌纤维化及TGF-β1/Smads信号通路的影响OA

Effect of Bushen Huoxue Formula(补肾活血方)on Myocardial Fibrosis and TGF-β1/Smads Signaling Pathway in Rats with Heart Exhaustion After Myocardial Infarction

中文摘要英文摘要

目的 观察补肾活血方对心肌梗死后心力衰竭大鼠心肌纤维化及TGF-β1/Smads信号通路的影响.方法 12周龄雄性SD大鼠120只,应用随机数字法选择20只作为假手术组.其余100只大鼠行冠状动脉前降支结扎术,并结合饥饿及力竭式游泳造成心肌梗死后心力衰竭模型.实验成模大鼠共80只,随机分为模型组、西药组、中药高剂量组、中药中剂量组、中药低剂量组.中药高、中、低剂量组大鼠分别按中药浓度比4∶2∶1给予补肾活血方汤剂灌胃,西药组给予沙库巴曲缬沙坦钠片混悬液灌胃,模型组及假手术组给予等量蒸馏水灌胃.连续用药4周后,应用超声检测6组大鼠左室收缩末期内径(Left ventricular end systolic diameter,LVESD)、左室舒张末期内径(Left ventricular end diastolic diame-ter,LVEDD)、射血分数(Ejection fraction,EF)及短轴缩短率(Fractional shortening,FS),Masson染色法观察6组大鼠心肌纤维化程度,测定大鼠心肌胶原容积分数(Collagen volume fraction,CVF),蛋白质印迹(Western blotting,WB)法测定6组大鼠心肌组织TGF-β1、p-Smad2、p-Smad3、Collagen Ⅰ、Collagen Ⅲ蛋白表达水平,荧光定量聚合酶链反应(Polymerase chain reaction,PCR)法检测6组大鼠心肌组织Smad6 mRNA、Smad7 mRNA表达.结果 用药4周后,与假手术组比较,模型组大鼠LVESD、LVEDD均升高,EF、FS均降低,心肌结构紊乱、CVF升高,心肌组织TGF-β1、p-Smad2、p-Smad3、Collagen Ⅰ、CollagenⅢ蛋白表达增高,Smad6 mRNA、Smad7 mRNA表达降低(P<0.01);与模型组相比,西药组、中药各组大鼠LVESD、LVEDD均降低,EF、FS均升高,心肌结构整齐、胶原容积分数(CVF)降低,心肌组织TGF-β1、p-Smad2、p-Smad3、Collagen Ⅰ、Collagen Ⅲ 蛋白表达降低,Smad6 mRNA、Smad7 mRNA 表达升高(P<0.05 或 P<0.01);与中药高剂量组比较,中药中剂量组大鼠LVESD、LVEDD均升高,EF、FS均降低,心肌组织TGF-β1、p-Smad2、p-Smad3、Colla-gen Ⅰ、CollagenⅢ蛋白表达升高,Smad6 mRNA、Smad7 mRNA表达降低(P<0.01);与中药中剂量组比较,中药低剂量组大鼠 LVESD、LVEDD 均升高,EF、FS 均降低,心肌组织 TGF-β1、p-Smad2、p-Smad3、Collagen Ⅰ、Collagen Ⅲ蛋白表达升高,Smad6 mRNA、Smad7 mRNA表达降低(P<0.01或P<0.05).结论 补肾活血方可改善心肌梗死后心力衰竭大鼠心肌纤维化,其作用机制可能与补肾活血方抑制TGF-β1/Smads激活相关.

Objective To observe the effect of Bushen Huoxue Formula(补肾活血方)on myocardial fibrosis and TGF-β1/Smads signaling pathway in rats with heart failure after myocardial infarction.Method 120 male SD rats aged 12 weeks were pur-chased and 20 were selected as the sham surgery group using the random number method.The remaining 100 rats underwent an-terior descending coronary artery ligation,combined with starvation and exhaustive swimming to create a heart failure model after myocardial infarction.A total of 80 model rats were randomly divided into a model group,a Western medicine group,a Chinese medicine high dose group,a Chinese medicine medium dose group and a Chinese medicine low dose group.The rats in the Chi-nese medicine high,medium and low dose groups were given Bushen Huoxue Formula by gavage at a concentration ratio of 4∶2∶1.The western medicine group was given a suspension of sacubitril and valsartan sodium tablets by gavage.The model group and sham surgery group were given an equal amount of distilled water by gavage.After 4 weeks of continuous medication,ultrasound was used to detect the left ventricular end systolic diameter(LVESD),left ventricular end diastolic diameter(LVEDD),left ven-tricular ejection fraction(EF)and left ventricular short axis shortening rate(FS)in six groups.Masson staining was used to ob-serve the degree of myocardial fibrosis in the six groups and the collagen volume fraction(CVF)was measured.Western blotting(WB)was used to measure the protein expression levels of TGF-β 1,p-Smad2,p-Smad3,Collagen Ⅰ and Collagen Ⅲ in the myocardial tissue of the six groups.Fluorescence quantitative polymerase chain reaction(PCR)was used to detect the mRNA expressions of Smad6 and Smad7 in the myocardial tissue of the six groups.Results After 4 weeks of medication,compared with those of the sham surgery group,the levels of LVESD and LVEDD of the model group increased,while the levels of EF and FS de-creased.The myocardial structure was disordered,CVF increased,and the protein expressions of TGF-β1,p-Smad2,p-Smad3,Collagen Ⅰ and Collagen Ⅲ in myocardial tissue increased.The mRNA expressions of Smad6 and Smad7 decreased(P<0.01).Compared with those of the model group,the levels of LVESD and LVEDD of rats in the western medicine group and the Chinese medicine low,medium and high dose groups were reduced,while the levels of EF and FS were increased.The myocardial structure was neat,CVF was reduced,and the protein expressions of TGF-β1,p-Smad2,p-Smad3,Collagen Ⅰand Collagen Ⅲ in myocardial tissue was reduced.The expressions of Smad6 mRNA and Smad7 mRNA were increased(P<0.05 or P<0.01).Compared with the Chinese medicine high dose group,the Chinese medicine medium dose group showed an in-crease in the levels of LVESD and LVEDD,a decrease in the levels of EF and FS,an increase in the protein expressions of TGF-β1,p-Smad2,p-Smad3,Collagen Ⅰ and Collagen Ⅲ in myocardial tissue,and a decrease in mRNA expressions of Smad6 and Smad7(P<0.01).Compared with the Chinese medicine medium dose group,the Chinese medicine low dose group showed an increase in the levels of LVESD and LVEDD,a decrease in the levels of EF and FS,an increase in the protein expressions of TGF-β1,p-Smad2,p-Smad3,Collagen Ⅰ and Collagen Ⅲ in myocardial tissue,and a decrease in mRNA expressions of Smad6 and Smad7(P<0.01 or P<0.05).Conclusion Bushen Huoxue Formula can improve myocardial fibrosis in rats with heart failure after myocardial infarction,and its mechanism of action may be related to the inhibition of TGF-β1/Smads activa-tion by Bushen Huoxue Formula.

孔繁达;杨硕;张罗丹;张艳

山西省中医院,山西太原 030012辽宁中医药大学附属第四医院,辽宁沈阳 110101山西省中医院,山西太原 030012辽宁中医药大学附属医院,辽宁沈阳 110032

医药卫生

心力衰竭心肌梗死心肌纤维化TGF-β1Smads补肾活血方

heart failuremiocardial infarctionmyocardial fibrosisTGF-β1SmadsBushen Huoxue Formula(补肾活血方)

《中华中医药学刊》 2026 (4)

99-104,后插5,7

国家自然科学基金面上项目(82174241)山西省基础研究计划项目(202103021223452)

10.13193/j.issn.1673-7717.2026.04.022

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