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白术内酯I调节HIF-1α/VEGF信号通路对急性心肌梗死大鼠心肌损伤的影响

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目的:探讨白术内酯 I(Atr-I)调节缺氧诱导因子 1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路对急性心肌梗死(AMI)大鼠心肌损伤的影响。方法:大鼠分为对照组、AMI 组、Atr-I组、阿司匹林组、BAY87-2243 组、Atr-I+BAY87-2243 组,每组 18 只。除对照组外,其他组大鼠均采用结扎冠脉左前降支根部的方式构建AMI模型,建模1h后,开始处理,给药1 次/d,持续7d。超声心动图监测左室短轴缩短率(FS)、左室射血分数(LVEF)的变化;2,3,5-三苯基氯化四氮唑(TTC)染色检测大鼠心肌梗死面积百分数;HE 染色检测左心室心肌组织病理学变化;TUNEL 染色检测心肌细胞凋亡;ELISA检测大鼠左心室心肌组织中肌红蛋白(Mb)、乳酸脱氢酶(LDH)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β含量;Western blot 检测大鼠心肌组织匀浆中 HIF-1α、VEGF 蛋白表达。结果:与对照组相比,AMI组大鼠心肌损伤明显,FS、LVEF及HIF-1α、VEGF蛋白表达降低,心肌梗死面积百分数、Mb、LDH、TNF-α、IL-1β 含量升高(P<0。05);与 AMI 组相比,Atr-I 组、阿司匹林组大鼠心肌损伤有所改善,FS、LVEF及HIF-1α、VEGF蛋白表达升高,心肌梗死面积百分数、Mb、LDH、TNF-α、IL-1β含量降低,BAY87-2243 组对应指标变化趋势与上述相反(P<0。05);与Atr-I组相比,Atr-I+BAY87-2243 组大鼠心肌损伤加剧,FS、LVEF及HIF-1α、VEGF蛋白表达降低,心肌梗死面积百分数、Mb、LDH、TNF-α、IL-1β含量升高(P<0。05)。结论:Atr-I减轻AMI大鼠心肌损伤可能与激活 HIF-1α/VEGF 信号通路有关。
Effect of Atractylenolide I on Myocardial Injury in Rats with AMI through Adjusting HIF-1α/VEGF Signaling Pathway
Objective:To investigate the effect of atractylenolide I(Atr-I)on myocardial injury in a-cute myocardial infarction(AMI)rats by regulating hypoxia inducible factor-1 alpha(HIF-1α)/vascular en-dothelial growth factor(VEGF)signaling pathway.Methods:Rats were separated into control group,AMI group,Atr-I group,aspirin group,BAY87-2243 group,and Atr-I+BAY87-2243 group,with 18 rats in each group.Except for the control group,rats in all other groups were used to construct AMI models through ligating the root of the left anterior descending branch of the coronary artery.After 1 hour of modeling,treat-ment began,and the drug was administered once a day for 7 days.Echocardiography was applied to detect changes in left ventricular short axis shortening rate(FS)and left ventricular ejection fraction(LVEF);the percentage of myocardial infarction area in rats was detected by 2,3,5-triphenyl tetrazolium chloride(TTC)staining;HE staining was applied to detect pathological changes in left ventricular myocardial tissue;TUNEL staining was applied to detect myocardial cell apoptosis;ELISA was applied to detect the levels of myoglobin(Mb),lactate dehydrogenase(LDH),tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β)in left ventricular myocardial tissue;Western blot was applied to detect the expression of HIF-1α and VEGF pro-teins in myocardial tissue homogenate.Results:Compared with the control group,the myocardial injury was obvious in the AMI group,the FS,LVEF,the expression of HIF-1α and VEGF proteins decreased,the per-centage of myocardial infarction area,the contents of Mb,LDH,TNF-α,and IL-1β increased(P<0.05);compared with the AMI group,the myocardial damage in rats in Atr-I group and aspirin group improved,the FS,LVEF,the expression of HIF-1α and VEGF proteins increased,the percentage of myocardial infarction area,the contents of Mb,LDH,TNF-α and IL-1β decreased;the corresponding indexes of BAY87-2243 group showed the opposite trend(P<0.05);compared with the Atr-I group,the myocardial injury in the Atr-I+BAY87-2243 group was exacerbated,the FS,LVEF,the expression of HIF-1α and VEGF proteins de-creased,the percentage of myocardial infarction area,the contents of Mb,LDH,TNF-α,and IL-1β in-creased(P<0.05).Conclusion:Atr-I reduces myocardial injury in AMI rats,which may be related to the activation of the HIF-1α/VEGF signaling pathway.

Atractylenolide IHypoxia-inducible factor 1-alpha/vascular endothelial growth factor signaling pathwayAcute myocardial infarctionApoptosis

马伟谦、刘明、魏娟、张云青、严月娟

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河北省石家庄市平安医院, 河北 石家庄 050000

河北省石家庄市第五医院内科, 河北 石家庄 050000

白术内酯I 缺氧诱导因子1α/血管内皮生长因子信号通路 急性心肌梗死 凋亡

河北省中医药局项目

2024396

2024

河北医学
河北省医学会

河北医学

CSTPCD
影响因子:1.915
ISSN:1006-6233
年,卷(期):2024.30(4)
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