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香豆素醇通过调节 Notch1/Hes1 通路来保护心肌缺血再灌注损伤。

Patchouli alcohol protects against myocardial ischaemia-reperfusion injury by regulating the Notch1/Hes1 pathway.

机构信息

Electrocardiogram room of Department of Functional Examination, Tongde Hospital of Zhejiang Province, Hangzhou, China.

College of Pharmacy, Hangzhou Medical College, Hangzhou, China.

出版信息

Pharm Biol. 2022 Dec;60(1):949-957. doi: 10.1080/13880209.2022.2064881.

Abstract

CONTEXT

Patchouli alcohol (PA) has protective effects on cerebral ischaemia/reperfusion (I/R) injury, but its efficacy on myocardial ischaemia-reperfusion (MI/R) has yet to be addressed.

OBJECTIVE

To examine the therapeutic effect of PA on myocardial ischaemia-reperfusion (I/R) injury.

MATERIALS AND METHODS

C57BL/6 male mice were randomly divided into sham, MI/R, MI/R + PA-10, MI/R + PA-20 and MI/R + PA-40 groups. MI/R model was established by ligating the anterior descending coronary artery of the heart. stimulated IR cell model was constructed by using the rat cardiomyocyte H9C2 cell line. Mice in the treatment groups were intraperitoneally injected with PA (10, 20, 40 mg/kg) for 30 days then subjected to surgery, and cells in the experimental group were pre-treated with PA (1, 10 or 100 μmol/L). After treatment, mouse heart function, myocardial injury markers, myocardial infarction and Notch1/Hes1 expression, endoplasmic reticulum stress markers, and apoptosis-related proteins were determined.

RESULTS

, PA treatment improved hemodynamic parameter changes and myocardial enzymes, increased the left ventricular ejection fraction and left ventricular fractional shortening, reduced the left ventricular end-systolic diameter and inhibited CK-MB, cTnI and cTnT levels. In addition, PA attenuated myocardial tissue damage and apoptosis. PA treatment elevated Notch1, NICD and Hes1 levels and suppressed the levels of ATF4, p-PERK/PERK, and cleaved caspase-3/caspase-3 and .

DISCUSSION AND CONCLUSION

PA protects against MI/R, possibly by modulating ER stress, apoptosis and the Notch1/Hes1 signalling pathways. These findings indicate that PA may be a promising candidate for treating ischaemic heart diseases.

摘要

背景

香豆素醇(PA)对脑缺血再灌注(I/R)损伤具有保护作用,但它在心肌缺血再灌注(MI/R)中的疗效尚未得到解决。

目的

研究 PA 对心肌缺血再灌注(I/R)损伤的治疗作用。

材料和方法

将 C57BL/6 雄性小鼠随机分为假手术组、MI/R 组、MI/R+PA-10 组、MI/R+PA-20 组和 MI/R+PA-40 组。通过结扎心脏前降支冠状动脉建立 MI/R 模型。利用大鼠心肌细胞 H9C2 细胞系构建 IR 细胞模型。治疗组小鼠腹腔注射 PA(10、20、40mg/kg)30 天后进行手术,实验组细胞用 PA(1、10 或 100μmol/L)预处理。治疗后,检测小鼠心功能、心肌损伤标志物、心肌梗死和 Notch1/Hes1 表达、内质网应激标志物和凋亡相关蛋白。

结果

PA 治疗改善了血流动力学参数变化和心肌酶,提高了左心室射血分数和左心室缩短分数,降低了左心室收缩末期直径,并抑制了 CK-MB、cTnI 和 cTnT 水平。此外,PA 减轻了心肌组织损伤和凋亡。PA 治疗上调了 Notch1、NICD 和 Hes1 水平,并抑制了 ATF4、p-PERK/PERK 和 cleaved caspase-3/caspase-3 的水平。

讨论与结论

PA 对 MI/R 具有保护作用,可能是通过调节内质网应激、凋亡和 Notch1/Hes1 信号通路。这些发现表明,PA 可能是治疗缺血性心脏病的有前途的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a5/9122376/f579e8112c20/IPHB_A_2064881_F0001_B.jpg

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