Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
Department of Anatomy, College of Medicine, King Khalid University, P.O. 641, Abha, 61421, Saudi Arabia.
Biomed Pharmacother. 2018 May;101:920-928. doi: 10.1016/j.biopha.2018.03.010. Epub 2018 Mar 22.
This study investigated the effect of ghrelin on cardiomyocytes function, apoptosis and ultra-structural alterations of remote myocardium of the left ventricle (LV) of rats, 21 days post myocardial infarction (MI). Rats were divided into 4 groups as a control, a sham-operated rats, a sham-operated+ghrelin, an MI + vehicle and an MI + ghrelin-treated rats. MI was induced by LAD ligation and then rats were recievd a concomitant doe of either normal saline as a vehicle or treated with ghrelin (100 μg/kg S.C., 2x/day) for 21 consecutive days. Ghrelin enhanced myocardial contractility in control rats and reversed the decreases in myocardial contractility and the increases in the serum levels of CK-MB and LDH in MI-induced rats. Additionally, it inhibited the increases in levels of Bax and cleaved caspase 3 and increased those for Bcl-2 in the remote myocardium of rat's LV, post-MI. At ultra-structural level, while ghrelin has no adverse effects on LV myocardium obtained from control or sham-treated rats, ghrelin post-administration to MI-induced rats reduced vascular formation, restored normal microfilaments appearance and organization, preserved mitochondria structure, and prevented mitochondrial swelling, collagen deposition and number of ghost bodies in the remote areas of their LV. Concomitantly, in remote myocardium of MI-induced rats, ghrelin enhanced endoplasmic reticulum intracellular organelles count, decreased number of atrophied nuclei and phagocytes, diminished the irregularity in the nuclear membranes and inhibited chromatin condensation. In conclusion, in addition to the physiological, biochemical and molecular evidence provided, this is the first study that confirms the anti-apoptotic effect of ghrelin in the remote myocardium of the LV during late MI at the level of ultra-structural changes.
本研究旨在探讨 ghrelin 对心肌梗死后 21 天大鼠左心室（LV）远程心肌细胞功能、凋亡和超微结构改变的影响。将大鼠分为 4 组：对照组、假手术组、假手术+ghrelin 组、MI+vehicle 组和 MI+ghrelin 组。通过 LAD 结扎诱导 MI，然后大鼠连续 21 天接受生理盐水（作为载体）或 ghrelin（100μg/kg，皮下注射，每天 2 次）治疗。Ghrelin 增强了对照组大鼠的心肌收缩力，并逆转了 MI 诱导大鼠心肌收缩力降低和血清 CK-MB 和 LDH 水平升高。此外，它抑制了 Bax 和 cleaved caspase 3 水平的升高，并增加了 Bcl-2 在 LV 远程心肌中的水平。在超微结构水平上，ghrelin 对 LV 心肌无不良影响，无论是来自对照组还是假手术组，但 ghrelin 给药后，MI 诱导的大鼠减少了血管形成，恢复了正常的微丝形态和组织，保存了线粒体结构，并防止了线粒体肿胀、胶原沉积和 LV 远程区域的鬼体数量。同时，在 MI 诱导大鼠的 LV 远程心肌中，ghrelin 增加了内质网细胞内细胞器的数量，减少了萎缩细胞核和吞噬细胞的数量，减少了核膜的不规则性，并抑制了染色质凝聚。总之，除了提供的生理、生化和分子证据外，这是第一项研究，证实了 ghrelin 在 LV 远程心肌中在超微结构变化水平上对晚期 MI 的抗凋亡作用。
