Shikonin attenuates kidney tubular epithelial cells apoptosis, oxidative stress, and inflammatory response through nicotinamide adenine dinucleotide phosphate oxidase 4/PTEN pathway in acute kidney injury of sepsis model

氮氧化物4 烟酰胺腺嘌呤二核苷酸磷酸 氧化应激 蛋白激酶B 急性肾损伤 活性氧 细胞凋亡 化学 PI3K/AKT/mTOR通路 NADPH氧化酶 分子生物学 生物 医学 内分泌学 内科学 生物化学 氧化酶试验
作者
Yanqin Peng,Yuan Li,Hao Li,Junhua Yu
出处
期刊:Drug Development Research [Wiley]
卷期号:83 (5): 1111-1124 被引量:8
标识
DOI:10.1002/ddr.21936
摘要

Abstract Natural compounds were used in the treatment of acute kidney injury (AKI) caused by sepsis. This study investigated the function of shikonin from the roots of Arnebia purpurea in sepsis‐induced AKI model. The target genes of shikonin were predicted by traditional Chinese medicine integrative database (TCMID). The markers of kidney injury, oxidative stress, and inflammatory factors were measured by enzyme‐linked immunosorbent assay (ELISA). The pathological changes of kidney tubules were assessed by Hematoxylin and Eosin staining. Apoptosis of kidney tubular epithelial cells (KTECs) was detected by the terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling. Protein expression was measured by western blot. Shikonin significantly improved kidney injury induced by cecal ligation and perforation (CLP). Besides, shikonin reduced KTECs apoptosis, malondialdehyde (MDA), reactive oxygen species (ROS), interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) levels, while augmented SOD and IL‐10 levels. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase4 (NOX4) was predicted a target gene of shikonin. The expression of NOX4 was significantly inhibited in shikonin‐treated group and the levels of phosphatidylinositol 3,4,5‐trisphosphate 3‐phosphate and dual specificity protein phosphate (PTEN) and p‐p65 were decreased, while level of p‐Akt was elevated. In vitro experiments, shikonin inhibited cell apoptosis, inflammatory, and ROS in human HK‐2 cells and rat TECs. Shikonin downregulated expression of NOX4, PTEN and p‐p65, and upregulated p‐AKT and Bcl‐2 expression in HK2 cells treated with lipopolysaccharide (LPS). Moreover, overexpression of NOX4 enhanced the effect of LPS on the expression level of PTEN, p‐p65, p‐AKT, and Bcl‐2, which was reversed by the addition of shikonin. Taken together, shikonin could improve sepsis‐induced AKI in rats, and attenuate the LPS induced KTECs apoptosis, oxidative stress, and inflammatory reaction via modulating NOX4/PTEN/AKT pathway.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
汉堡包应助润润轩轩采纳,获得10
刚刚
jia关闭了jia文献求助
1秒前
2秒前
2秒前
FashionBoy应助hildelau采纳,获得30
2秒前
伊一发布了新的文献求助10
3秒前
3秒前
3秒前
3秒前
jdmeme发布了新的文献求助30
4秒前
4秒前
Bravejjq完成签到 ,获得积分10
4秒前
zhanghaoshan发布了新的文献求助10
4秒前
研友_nxy9XZ完成签到,获得积分10
5秒前
Breathe完成签到 ,获得积分10
5秒前
慕青应助will采纳,获得30
5秒前
5秒前
6秒前
石会发完成签到,获得积分10
6秒前
一片叶子发布了新的文献求助10
6秒前
潇洒的诗桃应助Jasmine采纳,获得20
7秒前
7秒前
糖果屋发布了新的文献求助10
7秒前
Bravejjq关注了科研通微信公众号
7秒前
是容与呀发布了新的文献求助10
8秒前
喜悦芝麻完成签到 ,获得积分10
9秒前
周其全完成签到,获得积分10
9秒前
wangdi应助亚迪采纳,获得10
9秒前
lhb发布了新的文献求助10
9秒前
彭鑫完成签到,获得积分10
10秒前
dpp发布了新的文献求助10
10秒前
10秒前
10秒前
10秒前
科研达人发布了新的文献求助10
10秒前
Wen发布了新的文献求助10
10秒前
11111完成签到,获得积分10
10秒前
鬼才L完成签到,获得积分20
11秒前
cycyong发布了新的文献求助10
11秒前
高分求助中
The late Devonian Standard Conodont Zonation 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 1000
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3246715
求助须知:如何正确求助?哪些是违规求助? 2889973
关于积分的说明 8261471
捐赠科研通 2558510
什么是DOI,文献DOI怎么找? 1387250
科研通“疑难数据库(出版商)”最低求助积分说明 650516
邀请新用户注册赠送积分活动 627024