Cornus Officinalis Iridoid Glycosides Protect against Chronic Renal Failure in Rats by Activating the Nrf2-antioxidant Pathway.

IF 1 4区医学 Q4 MEDICAL LABORATORY TECHNOLOGY Annals of clinical and laboratory science Pub Date : 2024-11-01

Aiping Zhao, Yuliang Qiu, Jing Wu, Shangzheng Dai, Chu Lin, Wenjie Zhang, Pengfei Li

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Abstract

Objective: To investigate the therapeutic effects of Cornus officinalis iridoid glycosides (CIG) on rats with chronic renal failure (CRF).

Methods: CRF was induced in adult male Sprague Dawley rats by nephrectomy. The rats were randomly divided into six groups: sham, sham+high-dose CIG (120 mg/kg/d for 14 days), CRF, CRF+low-dose CIG (60 mg/kg/d for 14 days), CRF+high-dose CIG, and CRF+high-dose CIG+ML385 (an inhibitor of nuclear factor erythroid 2-related factor 2 (Nrf2), single administration at 30 mg/kg). The pathohistological changes in renal tissues were evaluated with histological staining. The biomarker levels of renal function, oxidative stress, inflammation, and apoptosis, as well as Nrf2 expression in renal tissues were determined.

Results: The rats in the sham and sham+high-dose CIG groups showed normal renal tissues. The rats in the CRF group displayed severe renal tissue damage/fibrosis and elevated biomarkers of renal dysfunction, which were accompanied by decreased nuclear and cytoplasmic Nrf2 expression and elevated levels of oxidative stress, inflammatory, and apoptotic markers in renal tissues. CIG treatment of CRF rats attenuated renal tissue damage and fibrosis, with the high-dose drug showing more significant improvements. The high-dose CIG also restored renal function in CRF rats, upregulated Nrf2, and downregulated oxidative stress, inflammatory, and apoptotic markers in renal tissues. These effects of high-dose CIG on CRF rats were reversed by ML385.

Conclusions: CIG activates the Nrf2-antioxidant pathway to ameliorate oxidative and inflammatory renal tissue damage and restore renal function in CRF rats.

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山茱萸环烯醚萜苷通过激活nrf2 -抗氧化途径预防大鼠慢性肾功能衰竭。

目的：探讨山茱萸环烯醚萜苷（CIG）对慢性肾功能衰竭大鼠的治疗作用。方法：采用大鼠肾切除术诱导成年雄性大鼠肾衰。将大鼠随机分为6组：假手术、假手术+高剂量CIG （120 mg/kg/d，连续14天）、CRF、CRF+低剂量CIG （60 mg/kg/d，连续14天）、CRF+高剂量CIG、CRF+高剂量CIG+ML385（核因子-红细胞2相关因子2 （Nrf2）抑制剂，单次给药，剂量为30 mg/kg）。采用组织染色法观察肾组织病理组织学变化。测定肾脏组织中肾功能、氧化应激、炎症和凋亡的生物标志物水平以及Nrf2的表达。结果：假药组和假药+大剂量CIG组大鼠肾脏组织正常。CRF组大鼠表现出严重的肾组织损伤/纤维化，肾功能障碍的生物标志物升高，并伴有核和细胞质Nrf2表达降低，肾组织中氧化应激、炎症和凋亡标志物水平升高。慢性肾功能衰竭大鼠经CIG治疗后，肾组织损伤和纤维化减轻，且大剂量药物改善更明显。大剂量CIG还能恢复CRF大鼠的肾功能，上调Nrf2，下调肾组织中的氧化应激、炎症和凋亡标志物。ML385可逆转大剂量CIG对CRF大鼠的影响。结论：CIG激活nrf2 -抗氧化途径，改善CRF大鼠肾组织氧化和炎症损伤，恢复肾功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of clinical and laboratory science 医学-医学实验技术

CiteScore

1.60

自引率

0.00%

发文量

112

审稿时长

6-12 weeks

期刊介绍： The Annals of Clinical & Laboratory Science welcomes manuscripts that report research in clinical science, including pathology, clinical chemistry, biotechnology, molecular biology, cytogenetics, microbiology, immunology, hematology, transfusion medicine, organ and tissue transplantation, therapeutics, toxicology, and clinical informatics.