Research progress of ginsenosides Rb1 in flap ischemia/reperfusion injury

doi:10.3969/j.issn.2095-4344.1077

Abstract

Abstract:

BACKGROUND: Ischemia/reperfusion injury is a common pathophysiological process in plastic surgery, which happens in random flap, free flap and composite tissue flap transplantation, even will lead to partial or whole flap necrosis. Ginsenosides Rb1 has been shown to exert protection in ischemia/reperfusion injuries of various tissues and organs.
OBJECTIVE: To review the mechanism of ischemia/reperfusion injury of flap and action mechanism of ginsenosides Rb1.
METHODS: CNKI and PubMed databases were searched for the articles published between January 1996 and June 2018 with the keywords of “ginsenosides, reperfusion injury, flaps” in English and Chinese, respectively. The articles addressing the pharmacological effects of ginsenosides Rb1, ginsenosides Rb1 alleviating tissue ischemia/reperfusion injury and flap ischemia/reperfusion injury were included.
RESULTS AND CONCLUSION: Flap ischemia/reperfusion injury is complex non-specific cascade damage after ischemic tissues restoring blood supply, which Involves in excessive production of oxygen free radicals, inflammation infiltration and its interaction with endothelial cells, energy failure, intracellular calcium overload, and nitric oxide production. Ginsenosides Rb1 has the effects of anti-oxidation, anti-inflammation and antiapoptosis. Ginsenosides Rb1 exerts good protection in ischemia/reperfusion injuries of various tissues and organs through anti-oxidation, anti-inflammation, increasing nitric oxide production, antiapoptosis, inhibiting calcium overload.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Ginsenosides, Reperfusion Injury, Surgical Flaps, Tissue Engineering

CLC Number:

R496

Cao Chang, Ren Xiaoyan, Meng Fanjun, Cheng Fengrui, Cen Ying. Research progress of ginsenosides Rb1 in flap ischemia/reperfusion injury[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(7): 1129-1135.

Figures/Tables 1

2.1 人参皂苷Rb1的药理作用人参是名贵补益类中药，其化学成分复杂，药理作用广泛。人参中的皂苷类成分被认为是人参中的主要有效物质，约占人参中成分的4%。人参皂苷根据皂苷元的不同，被分为二醇类皂苷、三醇类皂苷和齐墩果酸类皂苷。人参皂苷不仅广泛存在于人参的根、茎、叶、花、果实、种子中，还存在于红参、高丽参、西洋参、三七、绞股蓝等植物中[13]。人参皂苷Rb1属于二醇型皂苷，在40多种人参皂苷中含量最高，是人参发挥药效的主要成分，一直是中外学者研究的热点。人参皂苷Rb1具有显著的清除自由基、抗炎、抗凋亡、降血糖、抗肿瘤、促进性功能及提高免疫力等作用。人参皂苷Rb1在中枢神经系统中可发挥促智、神经损伤修复、脑缺血保护作；在心血管系统中发挥抗心肌凋亡、保护血管内皮细胞能作用[14]。大量动物实验研究已证实人参皂苷Rb1对脑、心、肝、肾、肠、皮瓣的缺血再灌注损伤都具有较好的保护作用[14-19]。 2.2 人参皂苷Rb1减轻组织器官缺血再灌注的研究进展 20世纪60年代，研究人员发现缺血组织或器官恢复血供后，将出现更加严重的损伤，并将此种现象定义为缺血再灌注损伤。皮瓣转移过程中，打破血流稳态，皮瓣将经历缺血缺氧过程，恢复血供后，将出现明显缺血再灌注损伤，理解皮瓣缺血再灌注损伤机制，有助于发现减轻皮瓣缺血再灌注损伤方法。研究表明缺血再灌注损伤是缺血组织或器官恢复血供后出现的一种复杂的非特异性损伤级联反应，多种因素促进缺血再灌注损伤的发生发展，主要涉及过量的氧自由基生成、炎症细胞激活浸润及其与内皮相互作用、能量衰竭、细胞内钙超载、一氧化氮生成、细胞凋亡等方面[1，15，20-21]。不同组织器官耐缺血不同，皮瓣对缺血耐受性更好。皮瓣缺血再灌注损伤机制与人参皂苷Rb1的作用机制可能与其抗氧化、抑制炎症反应、增加一氧化氮合成、抗凋亡、抑制钙超载等作用相关。 2.2.1 清除氧自由基、抑制脂质过氧化作用再灌注期间氧自由基过量生成是皮瓣缺血再灌注损伤中重要的致病因素。机体正常情况下可产生少量氧自由基，与体内抗氧化物质处于动态平衡，不会对机体造成损伤。当皮瓣处于缺血状态，细胞氧利用能力下降，引起有氧代谢障碍。此时氧原子失去了一个电子变成了具有可攻击细胞的活性氧自由基(ROS)，包括超氧阴离子、羟自由基等多种过氧化物，从而引发了一系列对细胞具有破坏性的过氧化反应。血流恢复灌注后，不仅没有减轻皮瓣的缺血缺氧状态，反而还提供了制造大量活性氧自由基的原料，导致细胞内大量的氧转化成活性氧自由基。活性氧自由基具有极其活泼的化学性质，可通过中间链式反应，不断形成新的自由基对组织造成损伤[22]。移植皮瓣发生缺血再灌注时，氧自由基的产生显著增多，机体抗氧化物质大量消耗，打破了机体自由基与抗氧化物质的动态平衡，进而通过氧化反应氧化细胞中脂质、蛋白质、核酸等成分引起细胞结构和功能损伤[23]。目前已知的活性氧自由基主要通过内皮细胞黄嘌呤氧化酶途径和中性粒细胞烟酰胺腺嘌呤二核苷酸磷酸还原酶(NADPH)两种途径造成皮瓣缺血-再灌注损伤。皮瓣组织缺血缺氧时一方面钙离子依赖性蛋白酶被激活，刺激黄嘌呤脱氢酶转化为黄嘌呤氧化酶；另一方面大量次黄嘌呤堆积，经黄嘌呤氧化酶氧化作用形成黄嘌呤，继而黄嘌呤氧化酶再催化黄嘌呤转化为尿酸[24]。除此之外，相关研究表明在线粒体缺血期可出现琥珀酸异常堆积，是再灌注初期自由基大量生成的启动因素[25]。缺血组织可从苹果酸-d冬氨酸穿梭(MAS)及嘌呤核糖循环(PNC)中产生大量延胡索酸，在琥珀酸脱氢酶逆向催化下生成琥珀酸。氧自由基还可通过以下途径对组织造成损伤：见表1。"

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