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Hydrogen-Rich Saline Ameliorates Hepatic Ischemia-Reperfusion Injury Through Regulation of Endoplasmic Reticulum Stress and Apoptosis

机译:通过调节内质网胁迫和凋亡来改善富含氢气的盐水改善肝缺血再灌注损伤

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Abstract Objective To evaluate the effect of hydrogen-rich saline (HS) on hepatic ischemia-reperfusion (I/R) injury. Methods Forty rats were randomly allocated into five groups: one sham group (control group), one group treated with 20?min of ischemia and normal saline (NS; I/R1?+?NS group), one group treated with 20?min of ischemia and HS (I/R1?+?HS group), one group treated with 60?min of ischemia and NS (I/R2?+?NS group), and one group treated with 60?min of ischemia and HS (I/R2?+?HS group). After reperfusion for 6?h, hepatic function, oxidative stress, pathological changes, and apoptosis of hepatic cells were evaluated. Furthermore, the expression levels of endoplasmic reticulum (ER) stress-associated proteins were identified. Results Serum ALT and AST levels and tissue MDA content in the I/R?+?HS groups were significantly lower than those in the I/R?+?NS groups. Pathological changes were also significantly ameliorated in the HS groups compared with those in the NS groups. Moreover, HS appeared to significantly attenuate hepatic I/R-induced ER stress responses, as indicated by the decreased expression of C/EBP homologous protein, protein-kinase-RNA-like ER kinase, and inositol-requiring protein-1α, as well as the increased expression of GRP78 proteins. Finally, the levels of apoptotic markers such as caspase-3 and TUNEL-positive cells were significantly lower in the HS groups than in the NS control groups, whereas the level of Bcl2 protein increased in the HS groups. Conclusion The protective effect of HS can be attributed to ER stress and apoptosis inhibition.
机译:摘要目的评价富含氢气(HS)对肝缺血再灌注(I / R)损伤的影响。方法将40只大鼠随机分配为五组:一个假手术组(对照组),用20次缺血和正常盐水(NS; I / R1?+ NS组)治疗一组,一组用20?分钟治疗缺血和HS(I / R1?+ + HS组),用60℃和NS(I / R2?+ NS组)治疗的一组,并用60次缺血和HS治疗一组( I / R2?+?HS组)。评估再灌注6ΩH,肝功能,氧化应激,病理变化以及肝细胞的凋亡。此外,确定了内质网(ER)应激相关蛋白的表达水平。结果I / R?+ + + + + + + + + NS组中的血清ALT和AST水平和组织MDA含量显着低于I / R?NS组。与NS组中的那些相比,HS组的病理变化也显着改善。此外,HS似乎显着衰减了肝脏I / R诱导的ER应激反应,如C / EBP同源蛋白,蛋白质 - 激酶-RNA样ER激酶的表达降低,也可以是肌醇需求的蛋白-1α所示作为GRP78蛋白的表达增加。最后,HS组中凋亡标记如凋亡标记的水平显着低于NS对照组,而BCL2蛋白的水平在HS组中增加。结论HS的保护作用可归因于ER应激和凋亡抑制。

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