芪参益气滴丸对糖尿病心肌缺血大鼠冠状动脉血流灌注及心功能的影响  

Effects of Qishen Yiqi Droplet on Coronary Blood Flow Perfusion and Cardiac Function in Diabetes Rats with Myocardial Ischemia

作　　者：刘甜甜 刘鑫 马丽娜 顾媛媛[1] 张彦丽[1] 巩颖[1] LIU Tiantian;LIU Xin;MA Lina;GU Yuanyuan;ZHANG Yanli;GONG Ying(Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学东方医院,北京100078

出　　处：《中西医结合心脑血管病杂志》2025年第4期539-546,共8页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金青年科学基金项目:(No.82104627);中央高水平中医医院临床科研业务费专项(No.DFGZRC-2024GJRC028);中央高校基本科研业务费专项(No.2022-JYB-XJSJJ-065)。

摘　　要：目的:探讨芪参益气滴丸改善糖尿病心肌缺血大鼠冠状动脉血流及心功能的作用机制。方法:将Wistar大鼠随机分为对照组、糖尿病心肌缺血组、阳性药组[尼可地尔片3.15 mg/(kg·d)]、芪参益气滴丸组[157.5 mg/(kg·d)]。对照组腹腔注射柠檬酸钠缓冲液,其余3组每日腹腔注射链脲霉素50 mg/(kg·d),连续注射3 d,建立糖尿病模型。予尼可地尔片和芪参益气滴丸灌胃干预17 d,第16天和第17天于大鼠颈背部皮下注射50 mg/(kg·d)异丙肾上腺素盐酸盐,建立心肌缺血模型,对照组颈背部皮下注射等剂量生理盐水。心脏超声检测各组大鼠心功能,于超声脉冲波多普勒模式下描记室间隔冠状动脉血流量。测定各组大鼠心肌损伤标志物血清心肌肌钙蛋白(I cTnI)、肌酸激酶同工酶(CK-MB)、天冬氨酸转氨酶(GOT)、一氧化氮(NO)含量。蛋白质免疫印迹法(Western Blot)检测心脏组织中沉默信息调节因子1(Sirt1)、蛋白激酶B(AKT)、AMP依赖的蛋白激酶(AMPK)α、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)、内皮型一氧化氮合酶(eNOS)蛋白表达。观察各组心脏病理变化、心肌凋亡、糖原累积、α-平滑肌肌动蛋白(α-SMA)及血管性血友病因子(vWF)表达情况。结果:与对照组相比,糖尿病心肌缺血大鼠射血分数、短轴缩短率、冠状动脉血流明显降低,血清中CK-MB、cTnI、GOT水平明显增加;心肌细胞肌纤维缺失明显,炎性细胞浸润增多,糖原沉积和心肌细胞凋亡数量增加,α-SMA和vWF标记的新生血管数量减少;心肌中Sirt1、p-AKT/AKT、p-AMPKα/AMPKα、PGC-1α、pS1177-eNOS表达升高,eNOS和NO水平降低。芪参益气滴丸干预明显改善了糖尿病心肌缺血缺氧心脏病变及心功能损伤。结论:芪参益气滴丸可能通过活化Sirt1/AMPK/eNOS信号,促使NO释放,抑制心肌细胞凋亡,逆转血管内皮损伤,增加内皮细胞迁移和侵袭功能,促进缺血区血管新生,进而增�Objective:To explore the effect of Qishen Yiqi Droplet on coronary blood flow and cardiac function in diabetes rats with myocardial ischemia.Methods:Wistar rats were randomly divided into control group,diabetes myocardial ischemia group,positive drug group[Nicorandil Tablets 3.15 mg/(kg·d)],and Qishen Yiqi Droplet group[157.5 mg/(kg·d)].The control group was intraperitoneally injected with sodium citrate buffer,and the other three groups were intraperitoneally injected with streptozotocin[50 mg/(kg·d)]every day for three consecutive days to establish the diabetes model.The myocardial ischemia model was established by oral administration of Nicorandil Tablets and Qishen Yiqi Droplet for 17 days.At the 16 th and 17 th days,isoproterenol hydrochloride 50 mg/(kg·d)was subcutaneously injected on the nape of the neck of rats,and the control group was subcutaneously injected with equivalent volume of normal saline.Cardiac ultrasound was used to detect the cardiac function of rats in each group,and ventricular septal coronary blood flow was recorded by pulsed wave Doppler mode.The serum levels of cardiac troponin I(cTnI),creatine kinase isoenzyme(CK-MB),glutamicoxaloacetic transaminase(GOT),and nitric oxide(NO)were measured.Cardiac pathological changes,myocardial apoptosis,glycogen accumulation,α-smooth muscle actin(α-SMA),and von Willebrand factor(vWF)expression were observed in each group.Western Blot was used to detect the protein expressions of silent information regulator 1(Sirt1),protein kinase B(AKT),AMP-activated protein kinaseα(AMPKα),peroxidase body increasing biological activated receptor-gammaɑauxiliary activation factor-1α(PGC-1α),and endothelial nitric oxide synthase(eNOS)in cardiac tissues.Results:Compared with the control group,the ejection fraction(EF),fraction shortening(FS),and coronary blood flow of diabetes rats with myocardial ischemia were significantly reduced,and the levels of CK-MB,cTnI,and GOT in serum were significantly increased.There was a significant loss of muscle fibers in myoc

关 键 词：心肌缺血 糖尿病 芪参益气滴丸 沉默信息调节因子1 AMP依赖的蛋白激酶 内皮型一氧化氮合酶 实验研究 

分 类 号：R285.5[医药卫生—中药学]