Effect of Yinchenhao decoction on renal oxidative stress injury in rats with obstructive jaundice and its mechanism of action based on the nuclear factor erythroid 2-related factor 2 signaling pathway
10.3969/j.issn.1001-5256.2023.05.019
- VernacularTitle:基于Nrf2信号通路探讨茵陈蒿汤对阻塞性黄疸大鼠肾氧化应激损伤的影响及其作用机制
- Author:
Junjian LIU
1
;
Shuai CHEN
2
;
Hongxia YUAN
3
;
Yan XU
4
;
Xibo ZHANG
1
;
Zhonglian LI
1
Author Information
1. Second Department of Hepatopancreatobiliary Surgery, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin 300100, China
2. Department of Thoracic Surgery, Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou, Jiangsu 221003, China
3. School of Management, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
4. Graduate School of Tianjin Medical University, Tianjin 300070, China
- Publication Type:Original Article_Biliary Disease
- Keywords:
Jaundice, Obstructive;
Renal Injury;
Yinchenhao Decoction;
Oxidative Stress;
Rats, Sprague-Dawley
- From:
Journal of Clinical Hepatology
2023;39(5):1126-1133
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Yinchenhao decoction on renal oxidative stress injury in rats with obstructive jaundice and its association with the regulation of the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear translocation. Methods A total of 32 male Sprague-Dawley rats were randomly divided into sham-operation group (S group), model group (O group), low-dose Yinchenhao decoction group (LY group), and high-dose Yinchenhao decoction group (HY group), with 8 rats in each group. For the rats in the S group, the upper common bile duct was isolated without ligation, and for those in the other groups, double ligation of the middle and upper 1/3 of the common bile duct was performed to establish a model of obstructive jaundice. After 7 days, the rats in the LY group and the HY group were given Yinchenhao decoction by gavage at a dose of 6.3 and 18.9 mL/kg, respectively, while those in the S and O groups were given an equal volume of distilled water by gavage every day for 7 consecutive days, and the rats were treated on day 14. ELISA was used to measure the serum levels of total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), and creatinine (Cr); spectrophotometry was used to measure the activity of the oxidative stress factors superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue; quantitative real- time PCR and Western blotting were used to measure the mRNA and protein expression levels of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in renal tissue; immunohistochemistry was used to measure observe the nuclear translocation of Nrf2 protein in renal tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further pairwise comparison within groups. Results Compared with the S group, the O group had significant increases in the levels of TBil, DBil, ALT、GGT, BUN, and Cr, a significant reduction in the activity of SOD, and a significant increase in the level of MDA (all P < 0.05). Compared with the O group, the LY group and the HY group had significant reductions in liver and renal function parameters, a significant increase in the activity of SOD, and a significant reduction in the level of MDA (all P < 0.05). Compared with the S group, the O group had significant reductions in the mRNA and protein expression levels of Nrf2 and NQO1 in renal tissue (all P < 0.05), and compared with the O group, the LY group and the HY group had significant increases in the mRNA and protein expression levels of Nrf2 and NQO1 (all P < 0.05), while there was no significant difference in the protein expression level of Keap1 between groups ( P > 0.05). Compared with the S group, the O group had a significant reduction in the positive rate of Nrf2 in cell nucleus in renal tissue ( P < 0.05), and compared with the O group, the LY group and the HY group had a significant increase in the positive rate of Nrf2 in cell nucleus ( P < 0.05). Conclusion Yinchenhao decoction can effectively alleviate renal injury caused by obstructive jaundice, possibly by upregulating the protein expression of Nrf2 in renal tissue and regulating the nuclear translocation of Nrf2 protein, so as to mediate the protein expression of downstream NQO1, regulate oxidative stress response caused by obstructive jaundice, and thereby alleviate renal injury in rats.
