Li Hui, Bai Ge, Ge Yansong, Zhang Qianzhen, Kong Xiangdong, Meng Weijing, Wang Hongbin
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin 150030, PR China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin 150030, PR China.
Life Sci. 2018 Feb 1;194:7-14. doi: 10.1016/j.lfs.2017.12.022. Epub 2017 Dec 15.
Our research investigated the role of Hydrogen-rich saline (HRS) on the Endoplasmic reticulum stress (ERS) pathway and the effect of HRS on tissue injury in small Bama pig model of hepatic ischemia-reperfusion combined with partial hepatectomy.
Eighteen healthy Bama miniature pigs were randomly divided equally into three groups: Sham, IRI, and HRS. Laparoscopic technique was employed to establish the model of hepatic ischemia-reperfusion combined with partial hepatectomy. HRS (10mL/kg) was injected into the portal vein 10min before perfusion. Histological examinations of the liver tissues were performed after HE staining. Additionally, transmission electron microscopy was performed to detect liver cell microstructure. Real-time PCR, Western blotting, and immunohistochemical staining were performed to analyze various ERS molecules including GRP78, p-eIF2α, XBP-1s, Full-length ATF6α, p-JNK, ATF4, and CHOP.
We observed that HRS visibly improved ischemia-reperfusion injury (IRI) by reducing various parameters of ERS stress as evidenced by down-regulation of the mRNA as well as protein levels of GRP78, p-eIF2α, XBP-1s, p-JNK, and CHOP, and reducing the cleavage of Full-length ATF6α.
Our study demonstrates that HRS protects the liver from IRI by inhibiting ERS.
本研究探讨富氢盐水(HRS)在内质网应激(ERS)途径中的作用,以及HRS对巴马小型猪肝缺血再灌注联合部分肝切除模型组织损伤的影响。
将18只健康巴马小型猪随机均分为三组:假手术组(Sham)、缺血再灌注组(IRI)和富氢盐水组(HRS)。采用腹腔镜技术建立肝缺血再灌注联合部分肝切除模型。在灌注前10分钟经门静脉注射HRS(10mL/kg)。对肝组织进行HE染色后进行组织学检查。此外,采用透射电子显微镜检测肝细胞微观结构。采用实时荧光定量PCR、蛋白质免疫印迹法和免疫组织化学染色分析包括GRP78、p-eIF2α、XBP-1s、全长ATF6α、p-JNK、ATF4和CHOP在内的各种ERS分子。
我们观察到,HRS通过降低ERS应激的各种参数,明显改善了缺血再灌注损伤(IRI),这表现为GRP78、p-eIF2α、XBP-1s、p-JNK和CHOP的mRNA及蛋白水平下调,以及全长ATF6α的裂解减少。
我们的研究表明,HRS通过抑制ERS保护肝脏免受IRI损伤。