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氢水对肌溶解导致的急性肾损伤具有保护作用

已有 4133 次阅读 2013-12-25 11:09 |个人分类:氢气生理盐水|系统分类:科研笔记

横纹肌溶解症俗称肌肉溶解,基本定义为因多种毒理学原因或机械刺激,引起骨骼肌细胞(即横纹肌)发生破裂。当骨骼肌被破坏时,肌红蛋白被释放到血液里,它会被肾脏滤过。由于肌红蛋白可能堵塞肾脏组织,导致急性管状骨疽、肾衰等病变。造成横纹肌溶解症的因素有很多:固定姿势压迫肌肉、过度运动、高压电电击、全身性痉挛、烧伤或被重物压伤以及部分药物不良反应等都有可能造成横纹肌溶解症。比较著名的是降脂药,如洛伐他汀、辛伐他汀和普伐他汀等羟甲戊二酰辅酶A(HMG-CoA)还原酶抑制剂对横纹肌有直接毒性作用,可致横纹肌溶解症。

注射高渗甘油是制备横纹肌溶解症动物模型的常用方法。研究发现,氧化应激和炎症反应在横纹肌溶解症病理生理过程中发挥重要作用,采用抗氧化药物如维生素C、促黑素、左旋肉硷和白藜芦醇对该疾病有一定治疗价值。虽然维生素C作为该疾病的治疗药物,但也会导致尿液酸化等不良作用。

2007年后发现氢对各类疾病治疗有效以来,有大量研究证明氢对许多类型肾损伤具有保护作用,但没有研究探讨对横纹肌溶解症肾脏损伤是否具有保护作用。最近来自解放军第88医院谷红霞等通过动物实验研究发现,氢可以通过抗氧化抗炎症途径对该疾病具有保护作用。该研究采用连续7天预先腹腔注射(5ml/kg/d, i.p.)(10ml/kg/d, i.p.)氢生理盐水的方法,通过检测肾脏功能、氧化应激和炎症因子等指标,确定氢对该疾病的治疗效果。虽然动物实验目前并不能说明人体的效果,但考虑到氢本身的安全性和在许多疾病以及人体实验中的效果,氢水对这一疾病的预防治疗价值值得深入研究。如果获得临床研究证实,将可以给这急性肾功能衰竭的治疗提供一种治疗手段。对某些可预见性肾脏损伤如剧烈运动、事故灾害等挤压伤患者预防肾脏损伤提供一种可行选择。也许在一些重大灾害事故中可以发挥积极意义。

Periodic acid-Schiff (PAS) staining of kidney sections (original magnification × 400). (a) control group (b) glycerol treated group (c) hydrogen-rich saline (HRS) (10ml/kg/d i.p.) treated group (d) HRS (5ml/kg/d i.p.) treated group.

该文章目前已经在线发表在Journal of Surgical Research

Pretreatment with hydrogen-rich saline reduces the damage caused by glycerol-ind.pdf

Pretreatment with hydrogen-rich saline reduces the damage caused by glycerol-induced rhabdomyolysis and acute kidney injury in rats

Rhabdomyolysis is a leading cause of acute kidney injury (AKI). The pathophysiological process involves oxidative stress and inflammation. Hydrogen-rich saline (HRS) is an antioxidant and anti-inflammatory. This study explored the protective effect of pretreatment with HRS on the development of glycerol-induced rhabdomyolysis AKI.

Materials and methods

48 rats were randomly divided into four equal groups. Group 1 served as the control, group 2 was given 50% Glycerol (10 ml/kg, i.m.), group 3 was given glycerol after 7 days pretreatment with high dose HRS (10ml/kg/d, i.p.), and group 4 was given glycerol after 7 days pretreatment with low dose HRS (5ml/kg/d, i.p.). Renal health was monitored by serum creatinine (Cr), urea and histological analysis, rhabdomyolysis by creatine kinase (CK) levels and. Oxidative stress was monitored by kidney tissue reactive oxygen species (ROS), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OH-dG), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) levels. Inflammation was monitored by interleukin -6 (IL-6) and tumor necrosis factor alpha (TNF -α) evaluation.

Results

Glycerol administration resulted in an increase in the mean histological damage score, serum Cr, Urea and CK, and kidney tissue ROS, MDA, 8-OH-dG, GSH-PX, IL-6 and TNF-α, and a decrease in kidney tissue SOD activity. All these factors were significantly improved by both doses of HRS but the mean histological damage score, urea, Cr, CK, ROS, 8-OH-dG, GSH-PX, IL-6 and TNF-α for the high dose HRS treatment group were even lower.

Conclusions

Pretreatment by HRS ameliorated renal dysfunction in glycerol-induced rhabdomyolysis by inhibiting oxidative stress and the inflammatory response.



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