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基于HIF/VEGF/eNOS信号通路探究附子-干姜药对抗心肌缺血再灌注损伤作用机制 被引量:3

Study on the mechanism of Fuzi-Ganjiang against myocardial ischemia-reperfusion in-jury based on HIFα/VEGF/eNOS signaling pathway
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摘要 目的揭示附子-干姜药对抗心肌缺血再灌注损伤(MI/RI)的作用机制,为附子干姜(FG)药对的后续研究与开发提供研究基础。方法采用大鼠心脏左前降支结扎模型造模、假手术组只穿针不结扎,其余组正常造模;将60只SD雄性大鼠随机分为6组,假手术组、模型组、附子-干姜低剂量组(1.4g/kg)、附子-干姜中剂量组(2.8g/kg)、附子-干姜高剂量组(5.6g/kg)、阳性组(复方丹参滴丸0.09g/kg);心电图仪观察造模后ST段是否抬高;TTC染色观察心肌组织梗死面积;苏木精-伊红(HE)染色观察心肌组织、血管组织病理损伤;试剂盒检测造模后血清中CK-MB、LDH、SOD、MDA表达;Western blot检测血管组织中HIF-α、VEGF、eNOS蛋白的表达。结果与假手术组相比,模型组心电图ST段抬高;心肌梗死面积增加(P<0.05),心肌组织及血管组织病理损伤增加;CK-MB、LDH、MDA表达明显升高、SOD表达降低(P<0.05);HIF-α、VEGF、eNOS蛋白的表达显著降低(P<0.05);与模型组相比,给药组心电图ST段降低;心肌梗死面积降低;心肌组织及病理组织损伤降低;CK-MB、LDH、MDA表达降低SOD表达增加;血管组织中HIF-α、VEGF、eNOS蛋白的表达显著增加(P<0.05)。结论附子-干姜药对可通过激活HIF-α/VEGF/eNOS信号通路促进MI/RI大鼠血管舒张发挥治疗作用。 Objective In order to reveal the mechanism of Fuzi-Ganjiang(FG)against myocardial ischemia-reperfusion injury(MI/RI)and provide a research basis for the follow-up study of FG.Methods The ligation model of the left anterior descending branch of the rat heart was used to establish the model.The sham operation group only had needles without ligation,and the other groups were established as normal.60 SD male rats were randomly divided into 6 groups,sham operation group,model group,FG low dose group(1.4g/kg),FG medium dose group(2.8g/kg),FG high dose group(5.6g/kg),positive group(Compound Danshen Dropping Pills,CDDP 0.09g/kg);ECG was used to observe whether ST was elevated after modeling;TTC staining was used to observe myocardial infarction area;hematoxylin-eosin(HE)staining was used to observe myocardial tissue and vascular tissue pathological damage;kits were used to detect serum CK-MB,the expressions of LDH,SOD and MDA;the expressions of HIF-α,VEGF and eNOS proteins in vascular tissue were detected by Western blot.Results Compared with the sham operation group,the ECG ST segment of the model group was elevated;the myocardial infarction area increased(P<0.05),and the path-ological damage of myocardial tissue and vascular tissue increased;the expressions of CK-MB,LDH,MDA and SOD were sig-nificantly increased.decreased(P<0.05);the expression of HIF-α,VEGF,eNOS proteins decreased significantly(P<0.05);Compared with the model group,the ST segment of the ECG in the administration group decreased;the myocardial infarction area decreased;the myocardial tissue and pathological tissue damage decreased;the expressions of CK-MB,LDH and MDA decreased,and the SOD expression increased;HIF-α,VEGF,eNOS in vascular tissue The expression of protein was sig-nificantly increased(P<0.05).Conclusion FG can activate HIF-α/VEGF/eNOS signaling pathway to promote vasodilation in MI/RI rats and play a therapeutic role.
作者 谢锋 张普 段广靖 李敏 兰卫 XIE Feng;ZHANG Pu;DUAN Guang-jing;LI Min;LAN Wei(School of Chinese Medicine,Xinjiang Medical University,Urumqi,830000,China;School of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang,712046,China)
出处 《时珍国医国药》 CAS CSCD 北大核心 2023年第9期2098-2102,共5页 Lishizhen Medicine and Materia Medica Research
基金 国家自然科学基金(81373988) 陕西省科技厅项目(2022SF-270) 陕西省中医药管理局项目(2022-QCYZH-050) 国家重点研发计划项目(2017YFC1703901-3)。
关键词 温阳通脉 附子干姜 血管舒张 心肌缺血再灌注损伤 Wen yang tong mai Fuzi-Ganjiang Vasodilation Myocardial ischemia-reperfusion injury
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