刘力华, 王东, 张美艳, 吴杨鹏, 邢甜甜, 王小闯. 4-甲酚减轻糖尿病大鼠心肌缺血/再灌注损伤[J]. 心脏杂志, 2023, 35(1): 9-14. DOI: 10.12125/j.chj.202203079
    引用本文: 刘力华, 王东, 张美艳, 吴杨鹏, 邢甜甜, 王小闯. 4-甲酚减轻糖尿病大鼠心肌缺血/再灌注损伤[J]. 心脏杂志, 2023, 35(1): 9-14. DOI: 10.12125/j.chj.202203079
    Li-hua LIU, Dong WANG, Mei-yan ZHANG, Yang-peng WU, Tian-tian XING, Xiao-chuang WANG. Gut microbial metabolite 4-cresol attenuates myocardial ischemia/reperfusion injury in diabetes[J]. Chinese Heart Journal, 2023, 35(1): 9-14. DOI: 10.12125/j.chj.202203079
    Citation: Li-hua LIU, Dong WANG, Mei-yan ZHANG, Yang-peng WU, Tian-tian XING, Xiao-chuang WANG. Gut microbial metabolite 4-cresol attenuates myocardial ischemia/reperfusion injury in diabetes[J]. Chinese Heart Journal, 2023, 35(1): 9-14. DOI: 10.12125/j.chj.202203079

    4-甲酚减轻糖尿病大鼠心肌缺血/再灌注损伤

    Gut microbial metabolite 4-cresol attenuates myocardial ischemia/reperfusion injury in diabetes

    • 摘要:
        目的  旨在研究4-甲酚对糖尿病(diabetic mellitus, DM)大鼠心肌缺血/再灌注(myocardial ischemia-reperfusion, MI/R)损伤的保护作用,并初步探讨其机制。
        方法  取雄性SD大鼠,分为正常对照组和糖尿病组。利用高脂饲料联合链脲霉素诱导2型糖尿病大鼠模型。造模成功后,随即分为3组:糖尿病假手术组(DM+Sham)、糖尿病心肌缺血/再灌注组(DM+MI/R)和糖尿病心肌缺血/再灌注+4-甲酚组(DM+MI/R+4-cresol)。4-cresol组采用植入式胶囊渗透压泵给药(5.5 mmol/L 4-cresol,0.15 µL/h),其余给予生理盐水。6周后,采用结扎冠状动脉左前降支30 min再灌注3 h的方法建立心肌缺血/再灌注模型。再灌注结束处死大鼠,检测心肌梗死和细胞凋亡。检测心肌氧化应激程度。测定心肌双底物特异性酪氨酸磷酸化调节激酶1a(dual specificity tyrosine-phosphorylation-regulated kinase 1A, Dyrk1A)表达以及细胞凋亡信号调节激酶1(apoptosis signal-regulating kinase, ASK1)磷酸化水平。
        结果  4-甲酚可有效减轻糖尿病大鼠心肌损伤,表现为心肌梗死面积下降、血清肌酸激酶(Ccreatine kinase, CK)及乳酸脱氢酶(Llactic dehydrogenase, LDH)活性降低、心肌细胞凋亡减少(P<0.05,P<0.01),同时4-甲酚显著抑制心肌丙二醛(malonic dialdehyde, MDA)含量(P<0.01),增加超氧化物歧化酶(superoxide Dismutase, SOD)含量、谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)含量(P<0.05,P<0.01),表明4-甲酚可以有效减轻氧化应激。此外,4-甲酚处理后,心肌Dyrk1A表达以及ASK1的磷酸化水平显著降低(P<0.05)。
        结论  4-甲酚可显著减轻糖尿病大鼠心肌缺血/再灌注损伤,其具体机制与激活Dyrk1A信号,抑制氧化应激,减轻细胞凋亡相关。

       

      Abstract:
        AIM   To observe the protective effect of 4-cresol on diabetic hearts following ischemia/reperfusion (I/R) and to explore the possible molecular mechanisms.
        METHODS   Forty-six male SD rats were randomly divided into normal control (CON) group and diabetes mellitus (DM) group. The DM rat model was induced by high-fat diet combined with a low-dose intraperitoneal injection of streptozotocin. Diabetic rats were randomly subdivided into three groups: Sham-operated DM rats (DM+Sham), DM+MI/R, and DM+MI/R+4-cresol (5.5 mmol/L 4-cresol, 0.15 µL/h). The MI/R model was established by coronary artery ligation. After 30 min of ischemia, the myocardium was reperfused for 3 h.
        RESULTS  4-cresol significantly attenuated myocardial injury in diabetes as evidenced by decreased infarct size, serum CK and LDH activities and cell apoptosis. Moreover, 4-cresol increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased malonaldehyde (MDA) in I/R hearts (P<0.05, P<0.01). Additionally, 4-cresol supplementation markedly inhibited dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A) expression and decreased the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) (P<0.05, P<0.01).
        CONCLUSION  4-cresol effectively inhibits Dyrk1A expression, reduces oxidative stress and cardiomyocyte apoptosis and eventually alleviates MI/R injury in diabetic hearts.

       

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