Peng Guan1, Zhi-Min Sun1, Li-Fei Luo1, Jian Zhou1, Shengchang Yang1, Ya-Shuo Zhao2, Fu-Yang Yu1, Ji-Ren An1, Na Wang1, En-Sheng Ji3. 1. Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, PR China. 2. Scientific Research Center, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, PR China. 3. Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, PR China. Electronic address: jesphy@126.com.
Abstract
AIMS: Hydrogen gas (H2) has a diversity of effects such as anti-apoptotic, anti-inflammatory and anti-oxidative properties. However, molecular mechanism underlying the potential effect of H2 on chronic intermittent hypoxia (CIH) induced renal injury remains obscure. MATERIALS AND METHODS: In the present study, adult male Sprague-Dawley rats were randomly allocated into four groups: control (CON) group, CIH group, CIH with H2 treatment (CIH + H2) group, and control with H2 treatment (CON + H2) group. Oxidative stress, autophagy and endoplasmic reticulum (ER) stress were detected to determine how H2 affected the renal function of CIH exposed rats. KEY FINDINGS: We demonstrated that rats who inhale hydrogen gas showed improved renal function, alleviated pathological damage, oxidative stress and apoptosis in CIH rats. Meanwhile, CIH-induced endoplasmic reticulum stress was decreased by H2 as the expressions of CHOP, caspase-12, and GRP78 were down-regulated. Furthermore, relative higher levels of LC3-II/I ratio and Beclin-1, with decreased expression of p62, were found after H2 administrated. Inhibition of mTOR may be involved in the upregulation of autophagy by H2. Finally, increased phosphorylation of p38 and JNK was involved in the CIH-induced pathological process. H2 could inhibit the activation of p38 and JNK, suggesting H2 played an active part in resisting renal injury via MAPK. SIGNIFICANCE: Taken together, our study reveals that H2 can ameliorate CIH-induced kidney injury by decreasing endoplasmic reticulum stress and activating autophagy through inhibiting oxidative stress-dependent p38 and JNK MAPK activation.
AIMS: Hydrogen gas (H2) has a diversity of effects such as anti-apoptotic, anti-inflammatory and anti-oxidative properties. However, molecular mechanism underlying the potential effect of H2 on chronic intermittent hypoxia (CIH) induced renal injury remains obscure. MATERIALS AND METHODS: In the present study, adult male Sprague-Dawley rats were randomly allocated into four groups: control (CON) group, CIH group, CIH with H2 treatment (CIH + H2) group, and control with H2 treatment (CON + H2) group. Oxidative stress, autophagy and endoplasmic reticulum (ER) stress were detected to determine how H2 affected the renal function of CIH exposed rats. KEY FINDINGS: We demonstrated that rats who inhale hydrogen gas showed improved renal function, alleviated pathological damage, oxidative stress and apoptosis in CIHrats. Meanwhile, CIH-induced endoplasmic reticulum stress was decreased by H2 as the expressions of CHOP, caspase-12, and GRP78 were down-regulated. Furthermore, relative higher levels of LC3-II/I ratio and Beclin-1, with decreased expression of p62, were found after H2 administrated. Inhibition of mTOR may be involved in the upregulation of autophagy by H2. Finally, increased phosphorylation of p38 and JNK was involved in the CIH-induced pathological process. H2 could inhibit the activation of p38 and JNK, suggesting H2 played an active part in resisting renal injury via MAPK. SIGNIFICANCE: Taken together, our study reveals that H2 can ameliorate CIH-induced kidney injury by decreasing endoplasmic reticulum stress and activating autophagy through inhibiting oxidative stress-dependent p38 and JNK MAPK activation.