Wujun Li1, Dong Li2, Liankang Sun3, Zeyu Li4, Liang Yu5, Shengli Wu6. 1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China; Department of General Surgery, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, PR China. Electronic address: liwujun2018@163.com. 2. Department of Hepatobiliary Surgery, The First People's Hospital of Xianyang City, Xianyang, 712000, PR China. Electronic address: lidong2000@163.com. 3. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China. Electronic address: sunliankang@126.com. 4. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China. Electronic address: lizeyu2003@163.com. 5. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China. Electronic address: 1507231762@qq.com. 6. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China. Electronic address: victorywu2000@163.com.
Abstract
BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury continued to be a significant clinical problem. The aim of this study was to examine whether the protective effects of 17-estradiol (E2) on hepatic ischemia/reperfusion (I/R) injury was associated with the downregulation of the angiotensin II (Ang II)/AT1R pathway. METHODS: Forty male Sprague Dawley rats were randomized into five groups: Sham operation, ischemia/reperfusion (I/R), I/R + E2, I/R + E2+estrogen receptor antagonist ICI 182,780 (ICI), and I/R + E2+ Ang II subtype I receptor (AT1R) antagonist losartan (LOS) groups. A model of total hepatic I/R was established by portal pedicle clamping for 60 min followed by reperfusion. At onset of ischemia, rats were treated with vehicle, E2, or LOS. ICI was given 30 min before E2 administration. At 24 h after reperfusion, blood samples and liver tissues were collected and subjected to histological examination, biochemical assays, and Western blot assays. RESULTS: Compared with I/R group, the degree of hepatocyte damage, serum ALT and TNF-α levels, hepatic MDA level and MPO activity were decreased in I/R + E2 group (all p < 0.05). Moreover, the serum and liver Ang II levels and hepatic AT1R protein level in I/R + E2 group were also significantly reduced compared with I/R group (all p < 0.05). However, the protective effect of E2 could be abolished by ICI administration. In contrast, administration of LOS conferred similar, but not as effective as E2, protective effects on hepatic I/R injury, without affecting Ang II and AT1R levels. CONCLUSIONS: The salutary effects of E2 on hepatic I/R injury are mediated in part by downregulating the Ang II/AT1R pathway.
BACKGROUND:Hepatic ischemia/reperfusion (I/R) injury continued to be a significant clinical problem. The aim of this study was to examine whether the protective effects of 17-estradiol (E2) on hepatic ischemia/reperfusion (I/R) injury was associated with the downregulation of the angiotensin II (Ang II)/AT1R pathway. METHODS: Forty male Sprague Dawley rats were randomized into five groups: Sham operation, ischemia/reperfusion (I/R), I/R + E2, I/R + E2+estrogen receptor antagonist ICI 182,780 (ICI), and I/R + E2+ Ang II subtype I receptor (AT1R) antagonist losartan (LOS) groups. A model of total hepatic I/R was established by portal pedicle clamping for 60 min followed by reperfusion. At onset of ischemia, rats were treated with vehicle, E2, or LOS. ICI was given 30 min before E2 administration. At 24 h after reperfusion, blood samples and liver tissues were collected and subjected to histological examination, biochemical assays, and Western blot assays. RESULTS: Compared with I/R group, the degree of hepatocyte damage, serum ALT and TNF-α levels, hepatic MDA level and MPO activity were decreased in I/R + E2 group (all p < 0.05). Moreover, the serum and liver Ang II levels and hepatic AT1R protein level in I/R + E2 group were also significantly reduced compared with I/R group (all p < 0.05). However, the protective effect of E2 could be abolished by ICI administration. In contrast, administration of LOS conferred similar, but not as effective as E2, protective effects on hepatic I/R injury, without affecting Ang II and AT1R levels. CONCLUSIONS: The salutary effects of E2 on hepatic I/R injury are mediated in part by downregulating the Ang II/AT1R pathway.
Authors: Rafael González-Tajuelo; María de la Fuente-Fernández; Daniel Morales-Cano; Antonio Muñoz-Callejas; Elena González-Sánchez; Javier Silván; Juan Manuel Serrador; Susana Cadenas; Bianca Barreira; Marina Espartero-Santos; Carlos Gamallo; Esther F Vicente-Rabaneda; Santos Castañeda; Francisco Pérez-Vizcaíno; Ángel Cogolludo; Luis Jesús Jiménez-Borreguero; Ana Urzainqui Journal: Arthritis Rheumatol Date: 2020-01-28 Impact factor: 10.995