应用现代生物技术和设备测定和评估肝脏的心肌保护作用

Biological Technologies for Evaluating the Mechanisms of Liver-mediated Myocardial Protection

冠状动脉病变引起的心肌缺血可导致心肌细胞损伤和心功能衰退,但另一方面可激活心肌保护机制,抑制心肌死亡,改进心肌功能。哺乳动物有心源性和非心源性两种心肌保护机制。心源性机制包括心肌内保护分子释放及心肌干细胞激活。心肌保护分子可抑制心肌细胞死亡,而心肌干细胞可分化成心肌细胞,进而促进损伤心肌修复。非心源性心肌保护机制主要涉及系统器官和组织。骨髓和肝脏是目前发现的主要心肌保护器官。随着心肌缺血,骨髓可释放造血干细胞和血管内皮前体细胞于血液循环系统。这些细胞可以进入缺血性心肌,促进心肌修复。与此同时,肝脏可表达和释放心肌保护因子,并且能游离肝细胞于血液循环系统。肝脏释放的保护因子可作用于缺血心肌,减少心肌损伤。部分游离肝细胞可随血流进入缺血心肌。这些细胞可能在心肌局部释放保护因子,提升心肌保护因子的水平,因而达到迅速保护心肌的目的。在该项研究中,我们采用了两种主要生物技术和设备,包括cDNA microarray analysis和flowcytometry,来测定和评估肝脏对缺血心肌的保护作用。cDNA microarray analysis用于研发肝脏的心肌防护蛋白,而flow cytometry用于发现心肌缺血时循环的肝细胞。这些生物技术和设备在发现肝脏对缺血心肌的保护上起了至关重要的作用。这里,作者将主要讨论应用现代生物技术和设备对肝脏的心肌保护作用的测定和评估。

Myocardial ischemia, while causing cardiomyocyte injury, can activate innate protective mechanisms, enhancing myocardial tolerance to ischemic injury. Such mechanisms are present in not only the heart, but also remote organs such as the bone marrow and liver. Within the heart, ischemic and activated cells may upregulate and release cardioprotective factors, including adenosine and VEGF, which protect ischemic cardiomyocytes from injury and death. Resident cardiac stem cells can be activated to facilitate myocardial regeneration and improve cardiac function. Systemicorgans, such as the bone marrow and liver, also contribute to myocardial protection. The bone marrow can release hematopoietic and stromal stem cells to the circulation to enhance myocardial repair and regeneration. The liver can mobilize hepatic cells to the circulation and upregulate secretory cardioprotective factors, including AGP2, BMPER, FGF21, NRG4, and TFF3, which protect ischemie myocardium from injm＇y. This article addresses primarily the mechanisms of liver-mediated myocardial protection. In these investigations, the use of biological technologies, including cDNA microarray and flow cytometry, greatly facilitated the discovery of the eardioprotective mechanisms.