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Effect and mechanism of Ganshuang Granule alleviated chronic liver injury via Nrf2/HO-1 signal pathway |
Hits 1170 Download times 747 Received:September 28, 2020 |
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DOI
10.11656/j.issn.1673-9043.2021.01.20 |
Key Words
Ganshuang Granule;CCL4;chronic liver injury;oxidative stress |
Author Name | Affiliation | E-mail | LIU Xiaokun | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China Tianjin Second People's Hospital, Tianjin 300192, China | | WANG Lixin | Tianjin Second People's Hospital, Tianjin 300192, China | crxyk@126.com |
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Abstract
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[Objective] This study was designed to investigate the protective and mechanism of Ganshuang Granule (GSG) on mice with chronic liver injury (CLI) caused by CCL4.[Methods] Fifty balb/c mice were divided into five groups:normal group,CHI group,low-dose Ganshuang Granule group,medium-dose Ganshuang Granule group and high-dose Ganshuang Granule group. Mice in all groups except for the normal group were intraperitoneal injected with 20% CCL4 olive oil solution (2 mL/kg),twice a week for 6 weeks to establish a mouse model of CLI. After the model was established,normal group and CHI group were given normal saline daily,and each dose of Ganshuang Granule group was given 1 g/kg,2 g/kg and 4 g/kg daily for four weeks. After 4 weeks intervention,blood and liver were collected. The serum transaminase level in each group was detected,and liver index was calculated. Meanwhile,pathological changes of mice liver were observed by HE staining,so as to study the therapeutic effect of GSG on mice with CLI. In addition,the contents of SOD,GSH-Px and MDA in liver homogenate were detected to study the effect of GSG on oxidative damage in mice with CLI. The Nrf2,HO-1,Gclc and NQO1 genes that related to the Nrf2/HO-1 signaling pathway in liver tissues were detected by RT-qPCR to preliminarily explore the mechanism of GSG in alleviating CLI.[Results] Compared with the normal group,serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the CLI group were significantly increased(P<0.05 or P<0.01). Hepatocytes showed extensive edema and partial nuclear fragmentation and necrosis. The activity of SOD and GSH-Px in liver homogenate decreased (P<0.01),while the level of MDA increased significantly (P<0.01). The gene expressions of Nrf2,HO-1,Gclc and NQO1 were significantly down-regulated (P<0.01,P<0.05). Compared with the CLI group,the middle and high dose groups of Ganshuang Granule could significantly reduce the serum levels of AST and ALT in mice with CLI (P<0.01,P<0.05). Each dose group of Ganshuang Granule can reduce the level of MDA in liver tissues,and increase the activity of SOD and GSH-Px,and the expression of Nrf2,HO-1,Gclc and NQO1 genes (P<0.01,P<0.05).[Conclusion] GSG could alleviate CLI caused by CCL4,which potential mechanism may be to inhibit oxidative stress of hepatocytes by activating Nrf2/HO-1 signaling pathway. |
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