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目的：观察橙皮苷对2型糖尿病心肌缺血/再灌注损伤的保护作用及其对SIRT1/Nrf2/HO-1信号通路的影响。方法：SD大鼠空白组、模型组、缺血再灌注组、橙皮苷组、SIRT1抑制剂组和橙皮苷+SIRT1抑制剂组，每组10只。除空白组外，余下各组大鼠均通过高脂饮食联合链脲佐菌素腹腔注射复制2型糖尿病大鼠模型。随后采用左冠状动脉前降支结扎30 min和再灌注2 h构建心肌缺血/再灌注损伤模型。分别通过HE染色检测各组da鼠心肌组织病理形态的改变，试剂盒法检测血清LDH、CK-MB和心肌组织中SOD、GSH、MDA的水平，免疫组化和Western blot法检测心肌组织中4-HNE和SIRT1/Nrf2/HO-1信号通路中相关蛋白的表达丰度。结果：与缺血再灌注组大鼠相比，橙皮苷能够显著抑制心肌细胞坏死和炎症细胞浸润，降低LDH活性、CK-MB和MDA的水平，增加SOD活性、GSH含量和4-HNE蛋白的表达水平，差异均具有统计学意义（P<0.01）。此外，与缺血再灌注组相比，橙皮苷组SIRT1、Nrf2和HO-1蛋白的表达均显著上调，差异均具有统计学意义（P<0.01）。结论：橙皮苷通过激活SIRT1/Nrf2/HO-1信号通路抑制氧化应激，改善糖尿病心肌缺血再灌注损伤。
Abstract：Objective:To observe the protective effect of hesperidin on myocardial ischemia/reperfusion injury in type 2 diabetes mellitus and its effect on SIRT1/Nrf2/HO-1 signaling pathway. Methods:A total of 50 Sprague-Dawley(SD)rats were randomly assigned to the normal control group(NC),model group,ischemia-reperfusion group(IR),hesperidin group,SIRT1 inhibitor group and hesperidin plus SIRT1 inhibitor group. In addition to NC,the rats in the remaining groups were replicated by intraperitoneal of high-fat diet combined with injection of streptozotocin for type 2 diabetic rats. Then,the myocardial ischemia/reperfusion injury(MIRI)rat model was established by LAd for 30 minutes with 2 hours reperfusion. HE staining was used to observe the pathological changes of myocardial tissue,and the levels of serum LDH,CK-MB and SOD,GSH and MDA in myocardial tissue were detected by kit methods,and the expression abundance of related proteins in 4-HNE and SIRT1/Nrf2/HO-1 signal pathway were detected by immunohistochemistry and Western blot. Results:Hesperidin could significantly inhibit cardiomyocyte necrosis and inflammatory cell infiltration,reduce LDH activity,CK-MB and MDA level,and increase SOD activity,GSH and 4-HNE level;the differences were statistically significant when compared with IR group(P<0.01). In addition,compared with the ischemia-reperfusion group,the expressions of SIRT1,Nrf2 and HO-1 proteins in hesperidin group were significantly upregulated;the differences were statistically significant(P<0.01). Conclusion:Hesperidin inhibits oxidative stress by activating SIRT1/Nrf2/HO-1 signaling pathway,and plays a protective effect of myocardial ischemia reperfusion injury in diabetic rats.
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基本信息:
DOI：10.13210/j.cnki.jhmu.20211119.002
中图分类号:R285.5
引用信息:
[1]马振旺,姜德友,胡丙成,等.橙皮苷通过SIRT1/Nrf2/HO-1信号通路改善2型糖尿病大鼠心肌缺血/再灌注损伤的机制研究[J].海南医学院学报,2022,28(08):566-571+578.DOI:10.13210/j.cnki.jhmu.20211119.002.
基金信息:
国家中医药管理局中医学术流派传承工作室建设项目（LPGZS2012-14）;国家中医药管理局全国名老中医药专家传承工作室建设项目~~
2021-11-20
2021-11-20
2021-11-20