Cai Zhaobin, Shi Tingting, Zhuang Rangxiao, Fang Hongying, Jiang Xiaojie, Shao Yidan, Zhou Hongping
Department of Cardiology, The Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese Medicine, Hangzhou, Zhejiang 310023, P.R. China.
Department of Pharmaceutical Preparation, The Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese Medicine, Hangzhou, Zhejiang 310023, P.R. China.
Exp Ther Med. 2018 Feb;15(2):1809-1818. doi: 10.3892/etm.2017.5653. Epub 2017 Dec 18.
With the development of science and technology, and development of artery bypass, methods such as cardiopulmonary cerebral resuscitation have been practiced in recent years. Despite this, some methods fail to promote or recover the function of tissues and organs, and in some cases, may aggravate dysfunction and structural damage to tissues. The latter is typical of ischemia-reperfusion (IR) injury. Lipid peroxidation mediated by free radicals is an important process of myocardial IR injury. Myocardial IR has been demonstrated to induce the formation of large numbers of free radicals in rats, which promotes the peroxidation of lipids within unsaturated fatty acids in the myocardial cell membrane. Markers of lipid peroxidation include malondialdehyde, superoxide dismutase and lactic dehydrogenase. Recent studies have demonstrated that N-acetylcysteine (NAC) is able to dilate blood vessels, prevent oxidative damage, improve immunity, inhibit apoptosis and the inflammatory response and promote glutathione synthesis in cells. NAC also improves the systolic function of myocardial cells and cardiac function, prevents myocardial apoptosis, protects ventricular remodeling and vascular remodeling, reduces opiomelanocortin levels in the serum and increases the content of nitric oxide in the serum, thus improving vascular endothelial function. Therefore, NAC has potent pharmacological activity; however, the relatively fast metabolism of NAC, along with its large clinical dose and low bioavailability, limit its applications. The present study combined NAC with medicinal activated carbons, and prepared N-acetylcysteine activated carbon sustained-release microcapsules (ACNACs) to overcome the limitations of NAC. It was demonstrated that ACNACs exerted greater effective protective effects than NAC alone on myocardial IR injury in rats.
随着科学技术的发展以及动脉搭桥技术的发展,近年来诸如心肺脑复苏等方法已得到应用。尽管如此,一些方法未能促进或恢复组织和器官的功能,在某些情况下,可能会加重组织的功能障碍和结构损伤。后者以缺血再灌注(IR)损伤为典型。自由基介导的脂质过氧化是心肌IR损伤的一个重要过程。心肌IR已被证明可在大鼠体内诱导大量自由基的形成,这促进了心肌细胞膜内不饱和脂肪酸中脂质的过氧化。脂质过氧化的标志物包括丙二醛、超氧化物歧化酶和乳酸脱氢酶。最近的研究表明,N-乙酰半胱氨酸(NAC)能够扩张血管、防止氧化损伤、提高免疫力、抑制细胞凋亡和炎症反应并促进细胞内谷胱甘肽的合成。NAC还可改善心肌细胞的收缩功能和心脏功能,防止心肌细胞凋亡,保护心室重塑和血管重塑,降低血清中阿片黑素皮质素水平并增加血清中一氧化氮的含量,从而改善血管内皮功能。因此,NAC具有强大的药理活性;然而,NAC相对较快的代谢速度,以及其较大的临床剂量和较低的生物利用度,限制了其应用。本研究将NAC与药用活性炭相结合,制备了N-乙酰半胱氨酸活性炭缓释微胶囊(ACNACs)以克服NAC的局限性。结果表明,ACNACs对大鼠心肌IR损伤的有效保护作用比单独使用NAC更强。