Yang Quan, Cao Yunshan
Department of Cardiovascular system, Beijing University International Hospital, Beijing 102206, China (Yang Q); Department of Cardiology, People' s Hospital of Gansu Province, Lanzhou 730000, Gansu, China (Cao YS). Corresponding author: Yang Quan, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017 Jun;29(6):501-505. doi: 10.3760/cma.j.issn.2095-4352.2017.06.005.
To approach the mechanisms and myocardial protective effect of Qishen Yiqi dropping pills on rats with myocardial infarction.
Sixty clean healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group and observation group (each n = 20). The rat model of acute myocardial infarction (AMI) was established by ligation of left anterior descent (LAD) branch of coronary artery. After modeling, the rats in observation group were given 0.135 g/kg of Qishen Yiqi dropping pills, and sham operation group and model group were administered the same amount of normal saline, once a day for consecutive 28 days. At the end of treatment, the levels of serum inflammatory factors of leukotriene B4 (LTB4), prostaglandin E (PGE), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay (ELISA); the changes of the indexes of hemodynamic [left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximal rate of increase/decrease in left ventricular pressure (±dp/dt max)], the ratio of the heart weight/body weight, and the ratio of the left ventricular weight/heart weight (LVW/HW), the myocardial infarction area, myocardial histopathological changes were observed in the three groups; myocardial tissues inflammatory related factors [the mRNA and protein expressions of cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX)], and the expression levels of transforming growth factor-β (TGF-β)/Smads signal transduction pathway related protein (TGF-β1, Smad2/3, Collagen I, Collagen III) and cell apoptosis related factors (Bcl-2, Bax) protein were measured.
Compared with the sham operation group, levels of serum inflammatory factors, the index of LVEDP, the ratio of the heart weight/body weight, LVW/HW, myocardial infarction area, the mRNA and protein expression levels of inflammatory factors in myocardium, the expression levels of TGF-β/Smads signal transduction pathway related protein and the cell apoptosis related factors protein in model group were all significantly elevated, while LVSP and ±dp/dt max were obviously decreased in model group. Compared with the model group, the levels of inflammatory factor in serum [LTB4 (ng/L): 370.11±46.98 vs. 633.23±83.37, PGE (ng/L): 48.75±26.35 vs. 131.25±29.75, TNF-α (μg/L): 177.28±22.65 vs. 248.47±16.21, IL-6 (μg/L): 493.22±165.99 vs. 638.41±191.66], LVEDP [mmHg (1 mmHg = 0.133 kPa): -2.03±2.98 vs. 7.03±1.39], the ratio of the heart weight/body weight [(6.53±0.11)% vs. (7.14±0.24)%], LVW/HW (0.26±0.01 vs. 0.32±0.02), myocardial infarction area [(27.21±2.87)% vs. (44.98±1.52)%], mRNA and protein expression of myocardial inflammatory factors, the expression of TGF-β/Smads signal transduction pathway related protein, and the protein expression of Bax were all significantly decreased in observation group (all P < 0.05), LVSP (mmHg: 129.01±11.93 vs. 108.11±12.69), the +dp/dt max (mmHg/s: 3 101.3±378.6 vs. 2 105.3±245.9), the -dp/dt max (mmHg/s: 2 612.4±249.7 vs. 1 654.4±188.1), while the protein expression of Bcl-2 in observation group were obviously increased (all P < 0.05). It was demonstrated by hematoxylin-eosin (HE) staining that there were no obvious pathological changes in the sham operation group; obvious infiltration of inflammatory factors in myocardium was shown in model group; pathological changes in the observation group were significantly improved as compared with those in the model group. It was shown by Masson staining that there were slight hyperplasia of myocardial fibers and no obvious pathological changes in the sham operation group. Severe collagen hyperplasia was found in model group, and the degree of fibrosis in the observation group was significantly improved.
Qishen Yiqi dropping pills can reduce the degree of myocardial fibrosis and inhibit the ventricular remodeling via TGF-β/Smads signal transduction pathway. The dropping pills can also suppress the release of inflammatory factors by reducing cPLA2 to decrease the inflammatory response and inhibit apoptosis and alleviate myocardial injury by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax.
探讨芪参益气滴丸对心肌梗死大鼠的作用机制及心肌保护作用。
将60只清洁级健康雄性Sprague-Dawley（SD）大鼠随机分为假手术组、模型组和观察组（每组n = 20）。采用结扎冠状动脉左前降支（LAD）的方法建立急性心肌梗死（AMI）大鼠模型。造模后，观察组大鼠给予0.135 g/kg芪参益气滴丸，假手术组和模型组给予等量生理盐水，连续给药28天，每日1次。治疗结束时，采用酶联免疫吸附测定（ELISA）法检测血清炎症因子白三烯B4（LTB4）、前列腺素E（PGE）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平；观察三组大鼠血流动力学指标[左心室收缩压（LVSP）、左心室舒张末期压力（LVEDP）、左心室压力最大上升/下降速率（±dp/dt max）]、心脏重量/体重比值、左心室重量/心脏重量比值（LVW/HW）、心肌梗死面积、心肌组织病理学变化；检测心肌组织炎症相关因子[胞质型磷脂酶A2（cPLA2）、环氧化酶-2（COX-2）、5-脂氧合酶（5-LOX）的mRNA和蛋白表达]，以及转化生长因子-β（TGF-β）/Smads信号转导通路相关蛋白（TGF-β1、Smad2/3、I型胶原、III型胶原）和细胞凋亡相关因子（Bcl-2、Bax）蛋白的表达水平。
与假手术组比较，模型组血清炎症因子水平、LVEDP指标、心脏重量/体重比值、LVW/HW、心肌梗死面积、心肌组织炎症因子mRNA和蛋白表达水平、TGF-β/Smads信号转导通路相关蛋白表达水平及细胞凋亡相关因子蛋白表达均显著升高，而模型组LVSP和±dp/dt max明显降低。与模型组比较，观察组血清炎症因子[LTB4（ng/L）：370.11±46.98比633.23±83.37，PGE（ng/L）：48.75±26.35比131.25±29.75，TNF-α（μg/L）：177.28±22.65比248.47±16.21，IL-6（μg/L）：493.22±165.99比638.41±191.66]、LVEDP[mmHg（1 mmHg = 0.133 kPa）：-2.03±2.98比7.03±1.39]、心脏重量/体重比值[（6.53±0.11）%比（7.14±0.24）%]、LVW/HW（0.26±0.01比0.32±0.02）、心肌梗死面积[（27.21±2.87）%比（44.98±1.52）%]、心肌炎症因子mRNA和蛋白表达、TGF-β/Smads信号转导通路相关蛋白表达及Bax蛋白表达均显著降低（均P < 0.05），LVSP（mmHg：129.01±11.93比108.11±12.69）、+dp/dt max（mmHg/s：3 101.3±378.6比2 105.3±245.9）、-dp/dt max（mmHg/s：2 612.4±249.7比1 654.4±188.1），而观察组Bcl-2蛋白表达明显升高（均P < 0.05）。苏木精-伊红（HE）染色显示，假手术组无明显病理改变；模型组心肌有明显炎症因子浸润；观察组与模型组比较，病理改变明显改善。Masson染色显示，假手术组心肌纤维轻度增生，无明显病理改变。模型组有严重的胶原增生，观察组纤维化程度明显改善。
芪参益气滴丸可通过TGF-β/Smads信号转导通路减轻心肌纤维化程度，抑制心室重构。该滴丸还可通过降低cPLA2抑制炎症因子释放，减轻炎症反应，上调Bcl-2表达、下调Bax表达抑制细胞凋亡，减轻心肌损伤。
