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药物后处理:缺血性损伤的分子方面。

Pharmacological postconditioning: a molecular aspect in ischemic injury.

机构信息

Chitkara College of Pharmacy, Chitkara University, Punjab, India.

出版信息

J Pharm Pharmacol. 2020 Nov;72(11):1513-1527. doi: 10.1111/jphp.13336. Epub 2020 Jul 28.

Abstract

OBJECTIVE

Ischaemia/reperfusion (I/R) injury is defined as the damage to the tissue which is caused when blood supply returns to tissue after ischaemia. To protect the ischaemic tissue from irreversible injury, various protective agents have been studied but the benefits have not been clinically applicable due to monotargeting, low potency, late delivery or poor tolerability.

KEY FINDINGS

Strategies involving preconditioning or postconditioning can address the issues related to the failure of protective therapies. In principle, postconditioning (PoCo) is clinically more applicable in the conditions in which there is unannounced ischaemic event. Moreover, PoCo is an attractive beneficial strategy as it can be induced rapidly at the onset of reperfusion via series of brief I/R cycles following a major ischaemic event or it can be induced in a delayed manner. Various pharmacological postconditioning (pPoCo) mechanisms have been investigated systematically. Using different animal models, most of the studies on pPoCo have been carried out preclinically.

SUMMARY

However, there is a need for the optimization of the clinical protocols to quicken pPoCo clinical translation for future studies. This review summarizes the involvement of various receptors and signalling pathways in the protective mechanisms of pPoCo.

摘要

目的

缺血/再灌注(I/R)损伤是指组织在缺血后血液供应恢复到组织时所造成的组织损伤。为了保护缺血组织免受不可逆损伤,已经研究了各种保护剂,但由于单靶点、效力低、延迟给药或耐受性差,这些保护剂的益处尚未在临床上得到应用。

主要发现

涉及预处理或后处理的策略可以解决保护治疗失败的问题。原则上,后处理(PoCo)在临床上更适用于发生意外缺血事件的情况。此外,PoCo 是一种很有吸引力的有益策略,因为它可以在主要缺血事件后通过一系列短暂的 I/R 循环在再灌注开始时迅速诱导,或者可以延迟诱导。已经系统地研究了各种药理学后处理(pPoCo)机制。使用不同的动物模型,大多数关于 pPoCo 的研究都是在临床前进行的。

总结

然而,需要优化临床方案,以加快 pPoCo 的临床转化,用于未来的研究。本综述总结了各种受体和信号通路在 pPoCo 的保护机制中的作用。

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