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目的:探讨硫酸锌联合阿司匹林治疗对大鼠急性心肌梗死的疗效及其机制。方法:选取100只200 g左右的雌性SD大鼠,随机分为5组,每组20只。假手术组不结扎并按常规饮食喂养,其余4组结扎并在常规饮食的基础上分别给以无菌蒸馏水(对照组)、硫酸锌、阿司匹林、硫酸锌联合阿司匹林,连续给药7 d后,使用超声心动图及侵入性导管检测心功能及血流动力学指标,并对大鼠血液中的肌钙蛋白T进行检测,然后取出心脏切片进行HE和Masson染色检验,检测各组心脏组织中的转化生长因子-β1(transforming growth factor-β1,TGF-β1)、环氧合酶-2(cyclooxygenase-2,COX-2)、超氧化物歧化酶1(superoxide dismutase-1,SOD-1)和谷胱甘肽过氧化物酶-4(glutathione peroxidase-4,GPX-4)的m RNA和蛋白质的表达情况。结果:给以阿司匹林和硫酸锌联合阿司匹林均能改善心肌梗死情况,保护受损心肌;与单独使用阿司匹林比较,硫酸锌联合阿司匹林更能显著提高收缩压[(119±11)mm Hg vs.(103±7)mm Hg,P=0.037]、舒张压[(98±4)mm Hg vs.(83±6)mm Hg,P=0.041]、平均动脉压[(103±6)mm Hg vs.(89±5)mm Hg,P=0.029]及Emax[(5.27±0.33)mm Hg/μL vs.(4.13±0.29)mm Hg/μL,P=0.027];降低炎性侵润、心肌梗死面积、心率[(328±11)beats/min vs.(364±19)beats/min,P=0.016]、全身血管阻力[(6.70±0.39)mm Hg×min/μL vs.(8.73±0.59)mm Hg×min/μL,P=0.039]及心肌梗死标志物肌钙蛋白T的水平[(583±51)pg/m L vs.(819±57)pg/m L,P=0.017];同时也更能降低促炎细胞因子TGF-β1和COX-2的m RNA[(0.65±0.18)vs.(1.48±0.12),P=0.014;(0.70±0.12)vs.(1.21±0.08),P=0.031]及蛋白[(2.42±0.19)vs.(3.61±0.27),P=0.032;(1.76±0.32)vs.(5.20±0.59),P=0.018)]表达水平,增加抗氧化酶SOD-1和GPX-4的m RNA[(2.14±0.11)vs.(1.58±0.12),P=0.021;(2.69±0.17)vs.(1.87±0.07),P=0.018]及蛋白[(5.40±0.62)vs.(2.40±0.33),P=0.036;(4.26±0.47)vs.(2.72±0.51),P=0.023]表达水平。结论:硫酸锌联合阿司匹林可有效保护急性心肌梗死对心肌的损伤,其主要的作用机制可能是通过抑制促炎细胞因子TGF-β1和COX-2,激活抗氧化酶类SOD-1和GPX-4的水平,实现抗炎抗氧化的作用,从而达到对急性心肌梗死的保护效果。
Objective: To investigate the curative effect and mechanism of zinc sulfate combined with aspirin on acute myocardial infarction in rats. Methods: A total of 100 female SD rats weighing about 200 g were randomly divided into 5 groups (20 in each group). The rats in the sham-operation group were not ligated and fed with the normal diet. The other four groups were ligated with sterilized distilled water (control group), zinc sulfate, aspirin and zinc sulphate together with aspirin on the basis of routine diet. After continuous administration for 7 days, Cardiac function and hemodynamic parameters were detected by echocardiography and invasive catheter, and the troponin T in blood was detected. HE staining and Masson staining were performed on the heart sections to detect the changes in cardiac tissue TGF-β1, COX-2, superoxide dismutase-1 (SOD-1) and Expression of m RNA and protein in glutathione peroxidase-4 (GPX-4). RESULTS: Both aspirin and zinc sulphate combined with aspirin improved myocardial infarction and protected the damaged myocardium. Compared with aspirin alone, zinc sulfate combined with aspirin significantly increased systolic blood pressure (119 ± 11) mm Hg vs. (103 The mean arterial pressure was (103 ± 6) mm Hg vs. (3 ± 6) mmHg, (P <0.05) 89 ± 5) mm Hg, P = 0.029] and Emax [(5.27 ± 0.33) mmHg / μL vs. (4.13 ± 0.29) mmHg / μL, respectively; P = 0.027]; decreased inflammatory infiltration, infarct size, Heart rate [(328 ± 11) beats / min vs. (364 ± 19) beats / min, P = 0.016] and systemic vascular resistance [(6.70 ± 0.39) mm Hg × min / μL vs. (8.73 ± 0.59) mm Hg × min / μL, P = 0.039], and the level of myocardial infarction marker troponin T [(583 ± 51) pg / m L vs. (819 ± 57) pg / m L, P = 0.017] (0.65 ± 0.18) vs. (1.48 ± 0.12), P = 0.014; (0.70 ± 0.12) vs. (1.21 ± 0.08), P = 0.031 ] And protein [(2.42 ± 0.19) vs. (3.61 ± 0.27), P = 0.032; (1.76 ± 0.32) vs. (5.20 ± 0.59, P = 0.018) The m RNA of GPX-4 [(2.14 ± 0.11) vs. (1.58 ± 0.12), P = 0.021; (2.69 ± 0.17) (1.87 ± 0.07), P = 0.018] and protein [(5.40 ± 0.62) vs. (2.40 ± 0.33), P = 0.036; (4.26 ± 0.47) vs. (2.72 ± 0.51), P = 0.023] Level. CONCLUSIONS: Combination of zinc sulfate and aspirin can effectively prevent myocardial injury induced by acute myocardial infarction. The main mechanism of action may be through the inhibition of proinflammatory cytokines TGF-β1 and COX-2, activation of antioxidant enzymes SOD-1 and GPX-4 The level of anti-inflammatory and anti-oxidant effect, so as to achieve the protection of acute myocardial infarction.