金雀异黄酮对心肌缺血再灌注损伤大鼠心肌细胞凋亡的影响
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国家自然科学基金面上项目 (81571183;81971225)


The effects of genistein on myocardial apoptosis in rats with myocardial ischemia reperfusion injury
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    摘要:

    【摘要】目的 探讨金雀异黄酮对心肌缺血再灌注损伤(MI/RI)大鼠心肌细胞凋亡Bcl2、Bax和Caspase3蛋白及mRNA表达的影响。方法 60只雄性SD大鼠分别为假手术组、模型组、阿司匹林组(10 mg·kg-1·d-1)、金雀异黄酮低剂量组(20 mg·kg-1·d-1)、中剂量组(40 mg·kg-1·d-1)和高剂量组(80 mg·kg-1·d-1),每组10只。给药2周后经典方法构建MI/RI大鼠模型后HE染色检测心肌组织;采集血清测乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同功酶(CKMB)和α羟丁酸脱氢酶(αHBD),采集心脏检测丙二醛(MDA)、超氧化物歧化酶(SOD)、总抗氧化能力(TAOC)和一氧化氮合酶(NOS);同时,RTPCR和Western Blotting检测心肌组织中Bcl2、Bax和Caspase3蛋白及mRNA表达。结果 假手术组心肌排列整齐无断裂,模型组出现大量断裂;与模型组相比,各治疗组明显改善;模型组大鼠血清LDH、CK、CKMB、αHBD高于假手术组(P<005),心肌MDA水平高于假手术组(P<005),心肌SOD、TAOC及 NOS水平均低于假手术组(P<005);与模型组比较,金雀异黄酮三个剂量组和阿司匹林组血清LDH、CK、CKMB、αHBD明显降低(P<005),心肌MDA明显降低(P<005),心肌SOD、TAOC及NOS明显升高(P<005);模型组大鼠心肌Bcl2蛋白和mRNA表达均低于假手术组(P<005),Bax和Caspase3蛋白和mRNA表达均高于假手术组(P<005),而金雀异黄酮三个剂量组和阿司匹林组Bcl2显著上调(P<005),Bax和Caspase3显著下调(P<005)。结论 金雀异黄酮可抑制心肌细胞凋亡,同时提高心肌抗氧化能力,抑制MI/RI给心肌带来的损伤。

    Abstract:

    【Abstract】Objective To investigate the effects of genistein on the proteins and mRNA expression of Bcl2, Bax and Caspase3 in myocardial of myocardial ischemia reperfusion injury (MI/RI) rats. Methods 60 male SpragueDawley rats were divided into sham operation group, model group, positive drug aspirin group (10 mg/kg/d), genistein low dose group (20 mg/kg/d), middle dose group (40 mg/kg/d) and high dose group (80 mg/kg/d). After 2 weeks of drug administration, the MI/RI rat model was constructed base on classical method, and then HE staining was used to detect myocardial pathology. The serum was collected for detecting the lactate dehydrogenase (LDH), Creatine kinase (CK), Creatine kinase isoenzymes (CKMB) and αhydroxybutyrate dehydrogenase (αHBD). The myocardial was collected for detecting the malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAOC) and nitric oxide synthase (NOS). The proteins and mRNA expression characteristics of Bcl2, Bax and Caspase3 were detected by RTPCR and Western Blotting. Results In the sham operation group, the myocardial arrangement was orderly without rupture, while in the model group, there were a lot of fractures. Compared with the model group, the serum LDH, CK, CK MB and α HBD of the model group were higher than those of the sham operation group (P<005), the myocardial MDA level was higher than that of the sham operation group (P<005), and the myocardial SOD, t AOC and NOS levels were lower than those of the sham operation group (P<005). Compared with the model group, LDH, CK, CK MB, αHBD, MDA, SOD, t AOC and NOS in the three dose groups of genistein and aspirin group were significantly decreased (P<005), while SOD, t AOC and NOS were significantly increased (P< 005). In the model group, the expression of Bcl2 protein and mRNA was lower than that in the sham operated group (P<005), and the expression of Bax and caspase3 protein and mRNA was higher than that in the sham operated group (P<005), while in the three dose groups of genistein and aspirin group, Bcl2 was significantly upregulated (P<005), Bax and caspase3 was significantly down regulated (P<005). ConclusionGenistein can inhibit myocardial cell apoptosis, increase myocardial antioxidant capacity, and inhibit myocardial ischemiareperfusion injury.

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  • 在线发布日期: 2020-02-13
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