目的 探究白藜芦醇（resveratrol, Res）预处理对大鼠心肌缺血再灌注损伤（myocardial ischemia reperfusion injury, MIRI）的影响。 方法 将42只健康成年雄性SD大鼠按随机数字表法分为4组：假手术组（Sham组，12只）、心肌缺血再灌注损伤组（IR组，12只）、白藜芦醇组（Res组，12只）和地尔硫卓组（阳性对照组，6只）。IR组、Res组和阳性对照组大鼠均采用结扎冠状动脉左前降支30 min再灌注2 h的方法建立MIRI模型，Sham组大鼠只穿线不结扎。建立MIRI模型前，Res组和阳性对照组大鼠连续7 d、每天分别腹腔注射1次Res（20 mg/kg ）和地尔硫卓（5 mg/kg），Sham组和IR组大鼠每天腹腔注射1次等容量二甲基亚砜（dimethyl sulfoxide, DMSO）溶液。4组大鼠于再灌注2 h时取腹主动脉血，采用ELISA法测定血清乳酸脱氢酶（lactate dehydrogenase, LDH）、肌酸激酶同工酶（creatine kinase isoenzyme, CK‑MB）浓度；取心肌组织测定心肌梗死面积，计算心肌梗死面积百分比。Sham组、IR组和Res组大鼠取心肌组织检测铁含量、丙二醛（malondialdehyde, MDA）含量和超氧化物歧化酶（superoxide dismutase, SOD）活性，采用Western blot法检测心肌组织谷胱甘肽过氧化物酶4（glutathione peroxidase 4, GPX4）、铁蛋白重链（ferritin heavy chain, FTH）、脂肪酸辅酶A连接酶4（fatty acid‑coenzyme A ligase 4, FACL4）蛋白水平。 结果 与Sham组比较：IR组、Res组、阳性对照组血清CK‑MB、LDH浓度升高（P<0.05），IR组、Res组心肌梗死面积百分比增大（P<0.05）；IR组心肌组织铁含量、MDA含量和FACL4蛋白水平升高（P<0.05），心肌组织SOD活性和FTH、GPX4蛋白水平降低（P<0.05）。与IR组比较：Res组和阳性对照组血清CK‑MB、LDH浓度降低（P<0.05），心肌梗死面积百分比减少（P<0.05）；Res组大鼠心肌组织铁含量、MDA含量和FACL4蛋白水平降低（P<0.05），SOD活性和FTH、GPX4蛋白水平升高（P<0.05）。其他指标比较差异无统计学意义（P>0.05）。 结论 Res预处理可降低大鼠心肌组织氧化应激水平以抑制铁死亡，从而减轻MIRI。
Objective To explore the effects of resveratrol (Res) pretreatment on myocardial ischemia reperfusion injury (MIRI) in rats. Methods Forty‑two healthy adult male SD rats were divided into four groups according to random number table method: a sham operation group (Sham group, n=12) , a myocardial ischemia reperfusion injury group (IR group, n=12), a resveratrol group (Res group, n=12) and a diltiazem group (positive control group, n=6). Rats in the IR group, the Res group and the positive control group were used to establish a MIRI model through ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. Rats in the Sham group were threaded without ligation alone. Before establishment of the MIRI model, rats in the Res group and the positive control group were intraperitoneally injected with 20 mg/kg resveratrol and 5 mg/kg diltiazem once per day for seven consecutive days, respectively. Those in the Sham group and the IR group were intraperitoneally injected with an equal volume of dimethyl sulfoxide (DMSO) solution once per day. Abdominal aortic blood samples were collected after reperfusion for 2 h, and the levels of serum lactate dehydrogenase (LDH) and creatine kinase isoenzymes (CK‑MB) were measuredby by enzyme‑linked immunosorbent assay (ELISA). Myocardial tissue was collected to calculate the percentage of myocardial infarct size, iron content, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity. Western blot was used to detect the levels of glutathione peroxidase 4 (GPX4), ferritin heavy chain (FTH), and fatty acid‑coenzyme A ligase 4 (fatty acid‑coenzyme A ligase 4, FACL4) in myocardial tissue. Results Compared with the Sham group: the IR group, Res group and positive control group showed increases in the levels of serum CK‑MB and LDH (P<0.05); IR group and Res group showed increases in the percentage of myocardial infarct size (P<0.05); IR group showed increases in the iron content, MDA content and FACL4 levels (P<0.05), and decreases in SOD activity and the levels of FTH and GPX4 in myocardial tissue (P<0.05). Compared with the IR group: the Res group and positive control group showed significant decreases in the levels of serum CK‑MB and LDH (P<0.005), and decreases in the percentage of myocardial infarct size (P<0.05); the Res groups presented remarkable decreases in the iron content, MDA content and FACL4 levels in myocardial tissue (P<0.05), and increases in SOD activity and the levels of FTH and GPX4 (P<0.05). There was no significant difference in other indexes (P>0.05). Conclusion Resveratrol pretreatment can relieve oxidative stress in rat myocardial tissue to inhibit ferroptosis, so as to reduce MIRI.
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