探索 miRNA 在维持高海拔缺氧相关疾病的氧化还原机制中的功能:循证研究

Richa Rathor, Geetha Suryakumar
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引用次数: 0

摘要

维持促氧化剂和抗氧化剂之间的平衡对有氧细胞的健康状态至关重要,因为如果这种平衡被打破,细胞就会面临氧化压力。在上升到高海拔地区的过程中,由于氧气供应不足,活性氧(ROS)增加,抗氧化系统下降。许多证据表明,高海拔缺氧会导致氧化还原平衡紊乱,从而引发各种疾病。与高海拔有关的疾病包括高海拔肺水肿(HAPE)、高海拔脑水肿(HACE)、急性高山病(AMS)、慢性高山病(CMS)、肺动脉高压、静脉血栓、睡眠障碍、肌肉萎缩等。许多补充剂,如维生素 C、维生素 E、白藜芦醇、β-胡萝卜素、槲皮素、乙酰基左旋肉碱、银杏叶、N-乙酰半胱氨酸、硒、灵芝、左旋肉碱、熊果酸等,都已被广泛研究用于对抗与高海拔有关的氧化应激。然而,大多数补充剂的益处有限。然而,由于 miRNAs 可调节能量代谢、新陈代谢途径、氧化应激、炎症等,因此 miRNA 可成为解决高海拔相关病理生理问题的答案。此外,miRNA 是一种易于评估、高度特异性和敏感性的小分子,也可用作生物标志物。考虑到问题的严重性,本研究筛选出了直接参与维持 NADPH 氧化酶(NOX)、一氧化氮合酶(NOS)、硫氧还蛋白诱导的一氧化氮合酶(NOS)的 miRNAs、本研究筛选出直接参与维持 NADPH 氧化酶(NOX)、一氧化氮合酶(NOS)、硫氧还蛋白(TXNIP)和抗氧化酶(包括超氧化物歧化酶(SOD)、过氧化氢酶、谷胱甘肽过氧化物酶(GPX)、过氧化还原酶(PRDX)、硫氧还蛋白(TXN)、硫氧还原酶(TXNRD))的 miRNA。在对筛选出的 miRNAs 进行分析后,提取了对 NOS、NOX 和 TXNIP 等产生自由基的酶有调节作用的 miRNA(12 个 miRNAs)。据此推测,调节 miRNA 可能是治疗高海拔相关疾病的一种方法。因此,需要在这一方向上开展进一步研究,以证明这一概念。
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Exploring miRNA function in maintaining redox mechanism of high altitude hypoxia associated maladies: An evidence based study

The maintenance of balance between pro-oxidants and antioxidants is paramount for healthy aerobic cell status as cell may face oxidative stress if this balance is disturbed. During ascent to high altitude, reactive oxygen species (ROS) is enhanced and antioxidant system declined due to low oxygen availability. A number of evidences suggested the role of high altitude hypoxia in various maladies due to perturbed redox homeostasis. High altitude associated maladies include High Altitude Pulmonary Edema (HAPE), High Altitude Cerebral Edema (HACE), Acute mountain sickness (AMS), chronic mountain sickness (CMS), pulmonary hypertension, venous thrombosis, sleep disorders, muscle atrophy etc. Many supplementations such as vitamin C, vitamin E, resveratrol, β-carotene, quercetin, acetyl-l-carnitine, Ginkgo biloba, N-acetyl cysteine, selenium, Ganoderma lucidum, l-carnosine, ursolic acid have been extensively researched for counteracting the high altitude associated oxidative stress. However, most of the supplementations are having limited beneficial effects. However, miRNA can become an answer for high altitude associated pathophysiological conditions as miRNAs regulate energy metabolism, metabolic pathways, oxidative stress, inflammation etc. On that, miRNAs are easily assessable, highly specific and sensitive small molecules that can also exploited as a biomarker. To consider the seriousness of the problem, the present study screened out the miRNAs that are directly involved in maintaining NADPH oxidases (NOX), nitric oxide synthases (NOS), thioredoxin induced protein (TXNIP) and antioxidants enzymes, comprising superoxide dismutase (SOD), catalase, glutathione peroxidise (GPX), peroxiredoxins (PRDX), thioredoxins (TXN), thioredoxin reductase (TXNRD). After analysis with the screened miRNAs, the extraction of miRNA (12 miRNAs) was done that have role in regulating free radical producing enzymes such as NOS, NOX and TXNIP. It is hypothesized that regulating miRNAs could become a probable answer for high altitude associated maladies. Hence, further research in this direction is required to proof the concept.

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