2型糖尿病大鼠心肌缺血再灌注损伤转录因子E2相关因子2/血红素氧合酶1信号通路的表达及白藜芦醇的干预研究
Expression of nuclear factor-E2 related factor 2/ heme oxygenase 1 signaling pathway in myocardial ischemia-reperfusion injury of type 2 diabetes mellitus rats and its intervention by resveratrol
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文摘
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目的探讨白藜芦醇在糖尿病心肌缺血再灌注(I/ R)损伤中对转录因子E2相关因子2(Nrf2)/血红素氧合酶1(HO-1)信号通路的影响。方法将2型糖尿病模型制备成功的60只大鼠分成假手术组、I/ R组、白藜芦醇(R)组、白藜芦醇+ EX527(RE)组,每组各15只。采用结扎左冠状动脉前降支30 min、恢复灌注120 min的方法制备心肌I/ R损伤模型。R组及RE组大鼠于术前7 d连续腹腔注射白藜芦醇15 mg/ kg,假手术组及I/ R组大鼠腹腔注射等容量的等渗NaCl溶液,RE组大鼠于缺血前15 min尾静脉注射EX527 1 μg/ kg。于再灌注120 min末,采用酶联免疫吸附测定法检测血清乳酸脱氢酶(LDH)及肌酸激酶同工酶(CK-MB)。随后处死大鼠取心肌组织,采用苏木素-伊红(HE)染色观察心肌病理学变化,采用2,3,5-氯化三苯基四氮唑法检测心肌梗死面积百分比,并检测心肌组织丙二醛含量及超氧化物歧化酶(SOD)活性。采用Westernblotting法检测各组大鼠心肌沉默信息调节因子1(SIRT1)、Nrf2及HO-1蛋白表达水平。结果HE染色可见,假手术组大鼠心肌细胞轻度断裂、水肿,少量炎症细胞浸润;I/ R组大鼠心肌纤维排列杂乱,心肌间质充血水肿伴大量炎症细胞浸润;R组大鼠心肌组织结构相对整齐,偶见核固缩;RE组大鼠心肌纤维排列杂乱,核固缩现象明显,炎症细胞浸润明显。假手术组大鼠无心肌梗死发生,I/ R组大鼠心肌梗死面积占比为(51 ± 6)%,R组大鼠占比为(37 ± 4)%,RE组大鼠占比为(41 ± 3)%,各组间比较差异有统计学意义(F = 160.703,P <0.001),R组及RE组大鼠心肌梗死的占比面积均显著小于I/ R组大鼠,且R组大鼠心肌梗死面积的占比更小(P均<0.05)。各组大鼠血清LDH、CK-MB、丙二醛、SOD、SIRT1、Nrf2及HO-1表达水平比较,差异均有统计学意义(F = 144.101、158.545、53.682、99.273、50.121、59.153、143.702,P均<0.001)。进一步两两比较发现,与假手术组比较,I/ R组、R组、RE组大鼠的LDH、CK-MB及丙二醛含量均显著升高,SOD活性、 SIRT1、Nrf2及HO-1蛋白表达水平均显著降低(P均<0.05);与I/ R组比较,R组及RE组大鼠的LDH、CK-MB及丙二醛含量均显著降低,SOD活性、SIRT1、Nrf2及HO-1蛋白表达水平均显著升高,且LDH、CK-MB及丙二醛含量在R组大鼠更低,SOD活性、SIRT1、Nrf2及HO-1蛋白表达水平在R组大鼠更高(P均<0.05)。结论白藜芦醇可通过促进SIRT1激活Nrf2/ HO-1信号通路来减轻2型糖尿病大鼠心肌的氧化应激反应及心肌I/ R损伤。 |
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其他语种文摘
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Objective To investigate the effect of resveratrol on the nuclear factor-E2 related factor 2(Nrf2)/ heme oxygenase 1(HO-1)signaling pathway in myocardial ischemiareperfusion(I/ R)injury of type 2 diabetes mellitus rats.Methods Sixty Sprague-Dawley rats with type 2 diabetes mellitus were randomly divided into a sham operation group, a I/ R group, a resveratrol preconditioning(R)group, and a resveratrol preconditioning + EX527(RE)group, 15 rats in each group.Myocardial I/ R injury was produced by ligating the left coronary anterior descending artery for 30 min followed by 120 min reperfusion.Rats in the R group and RE group were intraperitoneally injected with resveratrol(15 mg/ kg, once a day)for 7 days before the operation;rats in the sham operation group and I/ R group were intraperitoneally injected with the equal capacity of isotonic NaCl solution;rats in the RE group also received EX527(1 μg/ kg)by caudal vein injection at 15 min before ischemia.At the end of 120 min reperfusion, blood samples were taken for detecting the concentration of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)by the enzyme-linked immunosorbent assay.Then rats were sacrificed in each group;the pathological changes of myocardium were observed by hematoxylin-eosin(HE)staining and the myocardial infarct size was measured by 2,3,5-triphenyltetrazolium chloride.The levels of malondialdehyde and superoxide dismutase(SOD)were compared among the four groups.The expression levels of myocardial silent information regulator of transcription 1(SIRT1), Nrf2, and HO-1 protein were detected using Western-blotting.Results From HE staining, the myocardial cells were slightly broken and edematous, with a small amount of inflammatory cells in the sham operation group;the myocardial fibers were disorderly arranged, with myocardial interstitial congestion and edema infiltrated by a large number of inflammatory cells in the I/ R group;the myocardial tissue was relatively structurally neat, with occasional karyopyknosis in the R group;the myocardial fibers were arranged in a disorderly way, with obvious karyopyknosis and inflammatory cells in the RE group.No myocardial infarction occurred in the sham operation group.The myocardial infarct size in the I/ R group, R group, and RE group showed significant differences [(51 ± 6)%,(37 ± 4)%,(41 ± 3)%;F = 160.703, P <0.001].It was much smaller in the R group and RE group than in the I/ R group, and was smallest in the R group(all P <0.05).The levels of LDH, CKMB, malondialdehyde, SOD, SIRT1, Nrf2, and HO-1 all showed significant differences among the four groups(F = 144.101, 158.545, 53.682, 99.273, 50.121, 59.153, 143.702;all P <0.001).Compared with the sham operation group, the levels of LDH, CK-MB, and malondialdehyde increased obviously in the I/ R group, R group and RE group, and the levels of SOD, SIRT1, Nrf2, and HO-1 decreased(all P <0.05).Compared with the I/ R group, the levels of LDH, CK-MB, and malondialdehyde decreased obviously in the R group and RE group, which decreased most in the R group, and the levels of SOD, SIRT1, Nrf2, and HO-1 increased, which increased most in the R group(all P <0.05).Conclusion Resveratrol can alleviate oxidative stress and myocardial I/ R injury in type 2 diabetes mellitus rats by promoting SIRT1 to activate the Nrf2/ HO-1 signaling pathway. |
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来源
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中华危重症医学杂志(电子版)
,2020,13(4):247-252 【扩展库】
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DOI
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10.3877/cma.j.issn.1674-6880.2020.04.002
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关键词
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糖尿病,2型
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心肌缺血
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再灌注损伤
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白藜芦醇
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地址
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新疆维吾尔自治区人民医院麻醉科, 乌鲁木齐, 830001
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语种
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中文 |
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文献类型
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研究性论文 |
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ISSN
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1674-6880 |
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学科
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药学 |
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基金
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新疆自然科学基金
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文献收藏号
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CSCD:6823279
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参考文献 共
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