五味子油对马兜铃酸肾损伤的保护作用评价

Yan YANG; Fei-lin GE; Xiao-yan ZHAN; Wen-qing MU; Zhi-yong LI; Li LIN; Zi-ying WEI; Zhao-fang BAI; SUN Qin; Xiao-he XIAO

doi:10.1007/s11655-022-3574-z

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五味子油对马兜铃酸肾损伤的保护作用评价

Original Article | Updated：2022-06-27

- 五味子油对马兜铃酸肾损伤的保护作用评价
- Schisandra chinensis Oil Attenuates Aristolochic Acid Ⅰ-Induced Nephrotoxicity in vivo and in vitro
- Chinese Journal of Integrative Medicine 2022年28卷第7期页码：603-611
- Affiliations：
  
  1.School of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, Sichuan Province (646000), China
  2.Senior Department of Hepatology,the Fifth Medical Center of PLA General Hospital, Beijing(100039), China
  3.China Military Institute of Chinese Materia,the Fifth Medical Center of PLA General Hospital, Beijing(100039), China
- Author bio：
  
  Prof. SUN Qin, E-mail: zxyjhsq@swmu.edu.cn
- Funds：
  
  the Major National Science and Technology Project(2018ZX09101-002)
- DOI：10.1007/s11655-022-3574-z
  中图分类号：
- 纸质出版日期：2022-07-01，
  
  网络出版日期：2022-04-07，
  
  录用日期：2022-02-17
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Yan YANG, Fei-lin GE, Xiao-yan ZHAN, 等. 五味子油对马兜铃酸肾损伤的保护作用评价[J]. Chinese Journal of Integrative Medicine, 2022,28(7):603-611.

Yan YANG, Fei-lin GE, Xiao-yan ZHAN, et al. Schisandra chinensis Oil Attenuates Aristolochic Acid Ⅰ-Induced Nephrotoxicity in vivo and in vitro[J]. Chinese Journal of Integrative Medicine, 2022,28(7):603-611.
Yan YANG, Fei-lin GE, Xiao-yan ZHAN, 等. 五味子油对马兜铃酸肾损伤的保护作用评价[J]. Chinese Journal of Integrative Medicine, 2022,28(7):603-611. DOI： 10.1007/s11655-022-3574-z.

Yan YANG, Fei-lin GE, Xiao-yan ZHAN, et al. Schisandra chinensis Oil Attenuates Aristolochic Acid Ⅰ-Induced Nephrotoxicity in vivo and in vitro[J]. Chinese Journal of Integrative Medicine, 2022,28(7):603-611. DOI： 10.1007/s11655-022-3574-z.

摘要

目的:

评价五味子油 (Schisandra chinensis oil

SCEO) 对马兜铃酸Ⅰ (Aristolocholic acidⅠ

AAⅠ) 肾毒性的保护作用

并探索其作用机制.

方法:

采用随机数字表法将C57BL/6小鼠随机分为5组

分别为对照组、AAⅠ (模型) 组和AAⅠ+SCEO (0.25

0.5

1 g/kg) 组

每组5只. SCEO预保护2天

对照组与模型组给予羧甲基纤维素钠. 除对照组外

各组小鼠从第3天开始腹腔注射AAⅠ

连续5天. 实验结束后

HE及TUNEL染色观察肾组织形态及细胞凋亡情况; ELISA检测ALT、AST、BUN、SCR、GSH、MDA、SOD水平; ELISA、qPCR和Western blot检测肝组织CYP1A1、CYP1A2和NQO1的表达. 体外实验中

SCEO (40 μg/mL) 预保护12 h

12 h后除对照组外各组给予AAⅠ 40 μM/mL 48 h

实验结束后利用流式细胞术检测细胞凋亡和ROS水平.

结果:

在AAⅠ诱导的肾毒性小鼠肾组织中

SCEO 0.5 g/kg、1 g/kg显著改善AAⅠ导致的组织病理损伤

明显减少肾组织细胞凋亡

并显著降低血清中ALT、AST、BUN及SCR水平 (

0.01或

0.05) . SCEO 0.5 g/kg、1 g/kg减少了肾脏ROS生成

降低MDA并增加GSH和SOD (

0.01或

0.05) . SCEO 1 g/kg增加CYP1A1和CYP1A2的表达

降低NQO1水平 (

0.01或

0.05) . 此外

体外研究结果也表明

SCEO 40 μg/mL可抑制细胞凋亡和ROS生成 (

0.01或

0.05) .

结论:

SCEO 具有抑制AAⅠ肾损伤作用

其作用机制可能与调节代谢酶从而抑制细胞凋亡和ROS的产生相关.

Abstract

Objective:

To investigate the protective effects of

Schisandra chinensis

oil (SCEO) against aristolochic acid Ⅰ (AAⅠ)-induced nephrotoxicity

in vivo

and

in vitro

and elucidate the underlying mechanism.

Methods:

C57BL/6 mice were randomly divided into 5 groups according to a random number table

including control group

AAⅠ group

and AAⅠ+SCEO (0.25

0.5 and 1 g/kg) groups (n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration

while the control and AAⅠ groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AAⅠ (5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) staining

respectively. The levels of serum alanine aminotransferase (ALT)

aspartate aminotransferase (AST)

blood urea nitrogen (BUN)

and serum creatinine (SCr)

as well as renal malondialdehyde (MDA)

glutathione

r-glutamyl cysteingl+glycine (GSH)

and superoxide dismutase (SOD) were analyzed using enzyme-linked immunosorbent assay (ELISA). Expressions of hepatic cytochrome P450 1A1 (CYP1A1)

CYP1A2

and nad(p)hquinonedehydrogenase1 (NQO1) were analyzed using ELISA

quantitative real-time polymerase chain reaction (qPCR) and Western blot

respectively.

In vitro

SCEO (40 μg/mL) was added 12 h before treatment with AAⅠ (40 μmol/mL for 48 h) in human renal proximal tubule cell line (HK-2)

then apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry.

Results:

SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL

staining in the kidney tissues of mice with AAⅠ-induced nephrotoxicity

and reduced serum levels of ALT

AST

BUN and SCr (

0.01 or

0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney

containing MDA

GSH and SOD (

0.01 or

0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues (

0.01 or

0.05). Besides

in vitro

studies also demonstrated that SCEO 40 μg/mL inhibited apoptosis and ROS generation (

0.05 or

0.01).

Conclusions:

SCEO can alleviate AAⅠ-induced kidney damage both

in vivo

and

in vitro

. The protective mechanism may be closely related to the regulation of metabolic enzymes

thereby inhibiting apoptosis and ROS production.

关键词

Keywords

aristolochic acid ⅠnephrotoxicitySchisandra chinensis oilmetabolic enzymesapoptosisreactive oxygen species

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