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

Junjian LIU; Shuai CHEN; Hongxia YUAN; Yan XU; Xibo ZHANG; Zhonglian LI

doi:10.3969/j.issn.1001-5256.2023.05.019

Volume 39 Issue 5

May 2023

Turn off MathJax

Article Contents

Abstract

References

Article Navigation > Journal of Clinical Hepatology > 2023 > 39(5): 1126-1133

PDF( 2889 KB)

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

DOI: 10.3969/j.issn.1001-5256.2023.05.019

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

Research funding:

General Project National Natural Science Foundation of China (81273952);

Tianjin Applied Basic Research Diversified Investment Fund (21JCZDJC01150);

Scientific and Technological Project in Key Areas of Traditional Chinese Medicine of Tianjin Municipal Health and Health Committee (2019003);

Integrated Traditional Chinese and Western Medicine Project of Tianjin Municipal Health and Health Committee (2021042);

2022 Central Finance Transfer Payment Local Project

More Information

Corresponding author: LI Zhonglian, nkyylzl@163.com (ORCID: 0000-0001-5211-7612)
Received Date: 2022-10-05
Accepted Date: 2022-11-10
Published Date: 2023-05-20

Abstract

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.
- Jaundice, Obstructive,
- Renal Injury,
- Yinchenhao Decoction,
- Oxidative Stress,
- Rats, Sprague-Dawley

FullText(HTML)

References(19)

References

[1]	MARTÍNEZ-CECILIA D, REYES-DÍAZ M, RUIZ-RABELO J, et al. Oxidative stress influence on renal dysfunction in patients with obstructive jaundice: A case and control prospective study[J]. Redox Biol, 2016, 8: 160-164. DOI: 10.1016/j.redox.2015.12.009.
[2]	LU XL, JIANG YY, CAO Q. The role of oxidative stress and nuclear factor erythroid 2-related factor 2 in nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2020, 36(4): 924-927. DOI: 10.3969/j.issn.1001-5256.2020.04.048. 陆孝良, 蒋元烨, 曹勤. 氧化应激与核因子E2相关因子2在非酒精性脂肪性肝病中的作用[J]. 临床肝胆病杂志, 2020, 36(4): 924-927. DOI: 10.3969/j.issn.1001-5256.2020.04.048.
[3]	TURPAEV KT. Keap1-Nrf2 signaling pathway: mechanisms of regulation and role in protection of cells against toxicity caused by xenobiotics and electrophiles[J]. Biochemistry (Mosc), 2013, 78(2): 111-126. DOI: 10.1134/S0006297913020016.
[4]	CAI GS, WEI ZH, XIAO HM, et al. Study on the dose-efficacy relationship of Yinchenhao decoction in past dynasties[J]. J Liaoning Univ Tradit Chin Med, 2019, 21(1): 129-132. DOI: 10.13194/j.issn.1673-842x.2019.01.035. 蔡高术, 魏泽辉, 萧焕明, 等. 茵陈蒿汤历代剂量变化规律探讨[J]. 辽宁中医药大学学报, 2019, 21(1): 129-132. DOI: 10.13194/j.issn.1673-842x.2019.01.035.
[5]	LIU J, QU J, CHEN H, et al. The pathogenesis of renal injury in obstructive jaundice: A review of underlying mechanisms, inducible agents and therapeutic strategies[J]. Pharmacol Res, 2021, 163: 105311. DOI: 10.1016/j.phrs.2020.105311.
[6]	FAHMY SR. Anti-fibrotic effect of Holothuria arenicola extract against bile duct ligation in rats[J]. BMC Complement Altern Med, 2015, 15: 14. DOI: 10.1186/s12906-015-0533-7.
[7]	HUANG LP, XU YH, DENG MZ, et al. Research progress on chemical constituents, pharmacological mechanism and clinical application of Artemisiae Scopariae Herba[J]. Nat Prod Res Dev, 2021, 33(4): 676-690. DOI: 10.16333/j.1001-6880.2021.4.018. 黄丽平, 许远航, 邓敏贞, 等. 茵陈的化学成分、药理作用机制与临床应用研究进展[J]. 天然产物研究与开发, 2021, 33(4): 676-690. DOI: 10.16333/j.1001-6880.2021.4.018.
[8]	JIN LX, JIN LJ, LUAN ZQ, et al. Research progress on chemical constituents and pharmacology of rhubarb[J]. Inf Tradit Chin Med, 2020, 37(1): 121-126. DOI: 10.19656/j.cnki.1002-2406.200027. 金丽霞, 金丽军, 栾仲秋, 等. 大黄的化学成分和药理研究进展[J]. 中医药信息, 2020, 37(1): 121-126. DOI: 10.19656/j.cnki.1002-2406.200027.
[9]	SHI YP, KONG HT, LI HN, et al. Research progress on chemical composition and pharmacological effects of Gardenia jasminoides and predictive analysis on quality marker (Q-marker)[J]. Chin Tradit Herb Drug, 2019, 50(2): 281-289. DOI: 10.7501/j.issn.0253-2670.2019.02.003. 史永平, 孔浩天, 李昊楠, 等. 栀子的化学成分、药理作用研究进展及质量标志物预测分析[J]. 中草药, 2019, 50(2): 281-289. DOI: 10.7501/j.issn.0253-2670.2019.02.003.
[10]	LIU JJ, LI ZL, SHANG HT. Study on Yinchenhao decoction regulating bile acid metabolism and intervening the mitochondrial DNA damage in liver cells of rats with obstructive jaundice[J]. Tianjin Med J, 2020, 48(9): 839-842. DOI: 10.11958/20200487. 刘军舰, 李忠廉, 尚海涛. 茵陈蒿汤调节胆汁酸代谢并干预阻塞性黄疸大鼠肝细胞线粒体DNA损伤的研究[J]. 天津医药, 2020, 48(9): 839-842. DOI: 10.11958/20200487.
[11]	ZHANG XB, DUAN QL, LI ZL, et al. Expression of iNOS in the liver of rats with acute biliary obstruction[J]. Shandong Med J, 2013, 53(29): 19-21, 24. DOI: 10.3969/j.issn.1002-266X.2013.29.007. 张西波, 段启龙, 李忠廉, 等. 急性胆道梗阻大鼠肝脏iNOS的表达及意义[J]. 山东医药, 2013, 53(29): 19-21, 24. DOI: 10.3969/j.issn.1002-266X.2013.29.007.
[12]	ZHANG HY, ZHAO B, WANG YH, et al. Emodin inhibits inflammation and oxidative stress by regulating Nrf2/HO-1 and MAPKs[J]. Chin J Immunol, 2021, 37(9): 1063-1068. DOI: 10.3969/j.issn.1000-484X.2021.09.008. 张昊悦, 赵蓓, 王业皇, 等. 大黄素通过调节Nrf2/HO-1和MAPKs抑制炎症和氧化应激机制研究[J]. 中国免疫学杂志, 2021, 37(9): 1063-1068. DOI: 10.3969/j.issn.1000-484X.2021.09.008.
[13]	TAGUCHI K, YAMAMOTO M. The KEAP1-NRF2 system as a molecular target of cancer treatment[J]. Cancers (Basel), 2020, 13(1): 46. DOI: 10.3390/cancers13010046.
[14]	ZHOU J, WANG ZC, YIN YH. Discussion on prevention and treatment of diabetic nephropathy with Yiqi Huoxue method based on KEAP1-NRF2-ARE signaling pathway[J]. China J Chin Med, 2022, 37(4): 742-750. DOI: 10.16368/j.issn.1674-8999.2022.04.139. 周吉, 王子晨, 阴永辉. 基于Keap1-Nrf2-ARE信号通路探讨益气活血法防治糖尿病肾病[J]. 中医学报, 2022, 37(4): 742-750. DOI: 10.16368/j.issn.1674-8999.2022.04.139.
[15]	WANG D, LIU J, ZHANG XY, et al. Geniposide alleviates liver injuries in rats with severe pancreatitis through the Nrf2/ Keap1/ARE pathway[J]. J Changchun Univ Chin Med, 2022, 38(6): 631-635. DOI: 10.13463/j.cnki.cczyy.2022.06.011. 王丹, 刘捷, 张细元, 等. 栀子苷通过Nrf2/Keap1/ARE通路减轻重症胰腺炎大鼠的肝损伤[J]. 长春中医药大学学报, 2022, 38(6): 631-635. DOI: 10.13463/j.cnki.cczyy.2022.06.011.
[16]	BELLEZZA I, GIAMBANCO I, MINELLI A, et al. Nrf2-Keap1 signaling in oxidative and reductive stress[J]. Biochim Biophys Acta Mol Cell Res, 2018, 1865(5): 721-733. DOI: 10.1016/j.bbamcr.2018.02.010.
[17]	HU LF, WANG Y, REN RJ, et al. Anti-oxidative stress actions and regulation mechanisms of Keap1-Nrf2/ARE signal pathway[J]. J Int Pharm Res, 2016, 43(1): 146-152, 166. DOI: 10.13220/j.cnki.jipr.2016.01.022. 胡流芳, 王迎, 任汝静, 等. Keap1-Nrf2/ARE信号通路的抗氧化应激作用及其调控机制[J]. 国际药学研究杂志, 2016, 43(1): 146-152, 166. DOI: 10.13220/j.cnki.jipr.2016.01.022.
[18]	LU M, WANG P, QIAO Y, et al. GSK3β-mediated Keap1-independent regulation of Nrf2 antioxidant response: A molecular rheostat of acute kidney injury to chronic kidney disease transition[J]. Redox Biol, 2019, 26: 101275. DOI: 10.1016/j.redox.2019.101275.
[19]	MA H, YANG B, YU L, et al. Sevoflurane protects the liver from ischemia-reperfusion injury by regulating Nrf2/HO-1 pathway[J]. Eur J Pharmacol, 2021, 898: 173932. DOI: 10.1016/j.ejphar.2021.173932.

Relative Articles

[1]	Yu ZHANG, Yongfeng YANG. Thinking of the pathological diagnosis of unexplained liver cirrhosis[J]. Journal of Clinical Hepatology, 2023, 39(3): 498-503. doi: 10.3969/j.issn.1001-5256.2023.03.003
[2]	Xixuan WANG, Liangzi DING, Yang CHENG, Hao HAN, Jian YANG, Jiangqiang XIAO, Yi WANG, Ming ZHANG, Feng ZHANG, Yuzheng ZHUGE. Value of liver stiffness measured by acoustic radiation force impulse in diagnosis of cirrhotic portal hypertension[J]. Journal of Clinical Hepatology, 2022, 38(11): 2488-2492. doi: 10.3969/j.issn.1001-5256.2022.11.010
[3]	Jialing ZHOU, Bingqiong WANG, Yameng SUN, Tongtong MENG, Shanshan WU, Hong MA, Xiaojuan OU, Hong YOU, Jidong JIA, Xiaoning WU. Application value of liver stiffness measurement-to-platelet ratio index score in diagnosis of hepatitis B liver fibrosis and liver cirrhosis[J]. Journal of Clinical Hepatology, 2022, 38(7): 1529-1533. doi: 10.3969/j.issn.1001-5256.2022.07.014
[4]	Zhongjie YU, Wenxia ZHAO, Leixin FENG, Hanxiao WANG, Jianpeng LIU. Value of five noninvasive diagnostic methods for liver cirrhosis in diagnosis of traditional Chinese medicine syndrome types in patients with compensated hepatitis B cirrhosis[J]. Journal of Clinical Hepatology, 2022, 38(1): 104-109. doi: 10.3969/j.issn.1001-5256.2022.01.016
[5]	Yajie XU, Wenzheng YOU, Wanlei REN, Quanhe LONG, Xiangjun JIANG, Doudou HU. Application of pathological indicators based on liver biopsy in the diagnosis of cirrhotic portal hypertension[J]. Journal of Clinical Hepatology, 2021, 37(12): 2935-2938. doi: 10.3969/j.issn.1001-5256.2021.12.042
[6]	Yu WANG, Min WANG, Guanhua ZHANG, Fuliang HE, Xiaojuan OU, Jidong JIA. Clinical diagnosis, staging, and therapeutic principles of liver cirrhosis[J]. Journal of Clinical Hepatology, 2021, 37(1): 17-21. doi: 10.3969/j.issn.1001-5256.2021.01.004
[7]	NIU XingJie, LIU ZhiHui, CUI FengMei, LIU YaoMin, WANG YanFei, ZHANG GuoMin, LIU JinXia. Value of peripheral blood long non-coding RNA-LET in the diagnosis of chronic hepatitis B cirrhosis[J]. Journal of Clinical Hepatology, 2020, 36(12): 2709-2713. doi: 10.3969/j.issn.1001-5256.2020.12.014
[8]	Zhou ShengYun, Duan ZhiHui. Noninvasive diagnosis of esophageal varices in liver cirrhosis[J]. Journal of Clinical Hepatology, 2020, 36(8): 1842-1846. doi: 10.3969/j.issn.1001-5256.2020.08.036
[9]	Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Gastroenterology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Consensus on the diagnosis and therapy of hepatic fibrosis(2019)[J]. Journal of Clinical Hepatology, 2019, 35(10): 2163-2172. doi: 10.3969/j.issn.1001-5256.2019.10.007
[10]	Li JiaNa, Zheng RuiQi, Li Na, Hu YuLin. The biological characteristics of GP73 and its value in the diagnosis of liver fibrosis and cirrhosis[J]. Journal of Clinical Hepatology, 2019, 35(6): 1361-1364. doi: 10.3969/j.issn.1001-5256.2019.06.040
[11]	Zhang YaNan, Jiang Chang, Xu Ying, Gao YanHang. Early diagnosis of spontaneous bacterial peritonitis in liver cirrhosis[J]. Journal of Clinical Hepatology, 2019, 35(8): 1851-1853. doi: 10.3969/j.issn.1001-5256.2019.08.045
[12]	Liu HaiFeng, Xu YongSheng, Zhang Yue, Zhao XiaoJu, Liu Zhao, Li JinKui, Yan RuiFeng, Xu Kai, Lei JunQiang. Value of magnetic resonance morphological imaging in the diagnosis and differentiation of post-hepatitis B cirrhosis[J]. Journal of Clinical Hepatology, 2018, 34(12): 2587-2591. doi: 10.3969/j.issn.1001-5256.2018.12.016
[13]	Yang ErNa, Cao WuKui. Research advances in noninvasive diagnosis of hepatic fibrosis[J]. Journal of Clinical Hepatology, 2017, 33(11): 2209-2213. doi: 10.3969/j.issn.1001-5256.2017.11.035
[14]	Du JingHua, Nan YueMin. Novel molecular diagnostic markers for liver fibrosis[J]. Journal of Clinical Hepatology, 2017, 33(3): 445-450. doi: 10.3969/j.issn.1001-5256.2017.03.009
[15]	Zhang Hui, Jia Lei, Lu: Dong, Xu YouQing. Value of serum cancer antigen12-5 level in diagnosis of peritoneal effusion in patients with liver cirrhosis[J]. Journal of Clinical Hepatology, 2016, 32(11): 2118-2120. doi: 10.3969/j.issn.1001-5256.2016.11.022
[16]	Deng Han, Qi XingShun, Zhu Qiang, Guo XiaoZhong. Alternative methods for diagnosis of esophageal varices in patients with liver cirrhosis[J]. Journal of Clinical Hepatology, 2016, 32(8): 1468-1473. doi: 10.3969/j.issn.1001-5256.2016.08.007
[17]	Zhao Wei. Clinical significance of plasma and urine neutrophil gelatinase-associated lipocalin levels in diagnosis of acute kindney injury in patients with cirrhosis[J]. Journal of Clinical Hepatology, 2015, 31(11): 1874-1877. doi: 10.3969/j.issn.1001-5256.2015.11.025
[18]	Wang Shuai, Hu DaRong. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites[J]. Journal of Clinical Hepatology, 2015, 31(7): 1018-1022. doi: 10.3969/j.issn.1001-5256.2015.07.005
[19]	Cai JunJun, Han Tao. Diagnosis and treatment of acute kidney injury in patients with cirrhosis[J]. Journal of Clinical Hepatology, 2014, 30(12): 1352-1356. doi: 10.3969/j.issn.1001-5256.2014.12.030
[20]	Jia KeDong, Shi ShuXian, Ruan YouBing. Detection of sialic acid in hepatitis involved liver cirrhosis and its significance for HCC diagnosis[J]. Journal of Clinical Hepatology, 2005, 21(2): 101-103.

Supplements(0)

Cited By

Cited by

Periodical cited type(11)

1.	阳丽华，梁英，刘仁峰，刘志昂. 甲状腺癌与甲状腺肿患者相关实验室指标的比较分析. 甘肃医药. 2025(01): 53-55+59 .
2.	张海苗. HBV感染原发性肝癌患者血常规指标的检测意义. 包头医学院学报. 2024(02): 67-71 .
3.	戴倩梅，丁体龙，代雪枫，于莉，陈策. 高敏丙型肝炎病毒核糖核酸在丙型肝炎中的诊断价值. 检验医学与临床. 2024(04): 487-490 .
4.	李晓宇，黄秀香，叶迎宾. 血清壳多糖酶3样蛋白1和PLT的比值与FIB-4指数在慢性乙型肝炎轻、中度诊断效价的比较. 标记免疫分析与临床. 2024(09): 1693-1697 .
5.	何萍，徐瑞，华秋菊，姜璐，王维平. 红细胞分布宽度与血小板比值对终末期肾病维持性血液透析患者动静脉内瘘失功的预测分析. 中国医师进修杂志. 2024(11): 988-994 .
6.	岳丽，孙佳瑶，刘龙芳. 脑小血管病患者外周血GPR30 mRNA、PLR、NPAS4表达及与认知功能、短期预后的关系. 临床误诊误治. 2023(01): 69-74 .
7.	杨杨，刘付弟，曾方林. 人类免疫缺陷病毒/乙型肝炎病毒合并感染者CD4~+T细胞计数和乙型肝炎病毒复制、中性粒细胞与淋巴细胞比值水平的相关性. 中国医药导报. 2023(10): 145-148 .
8.	王跃帮，常珊碧，王梦林，崔倩，裴兵. RLR在HBV相关性肝硬化诊断中的应用. 热带医学杂志. 2023(10): 1451-1455 .
9.	邱建华. PLT联合凝血功能检测对早期肝硬化的诊断价值分析. 现代诊断与治疗. 2023(22): 3433-3435 .
10.	赵霄君，谢建刚，段楚君，刘善收，王倩梅，思艺，王林潇，吴丹，王一帆，李俊杰. 血常规指标与脓毒症患者短期预后的相关性研究. 临床误诊误治. 2022(08): 73-77 .
11.	邵林楠，张树婷，王霓，周世航，刘铭. 血细胞各比值对慢性丙型肝炎病毒患者肝纤维化程度的评估. 临床血液学杂志. 2022(12): 874-877 .

Other cited types(7)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(5) / Tables(3)

Get Citation

PDF

XML

Article Metrics

Article views (569) PDF downloads(46)

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

DOI: 10.3969/j.issn.1001-5256.2023.05.019