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槲皮素通过细胞色素c/半胱天冬酶-9/半胱天冬酶-3信号通路对镉诱导的肾细胞凋亡的保护作用。

Protective effect of quercetin on cadmium-induced renal apoptosis through cyt-c/caspase-9/caspase-3 signaling pathway.

作者信息

Huang Ruxue, Ding Lulu, Ye Ying, Wang Ke, Yu Wenjing, Yan Bingzhao, Liu Zongping, Wang Jicang

机构信息

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China.

College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

出版信息

Front Pharmacol. 2022 Aug 16;13:990993. doi: 10.3389/fphar.2022.990993. eCollection 2022.

DOI:10.3389/fphar.2022.990993
PMID:36052148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9425064/
Abstract

Cadmium (Cd), a heavy metal, has harmful effects on animal and human health, and it can also obviously induce cell apoptosis. Quercetin (Que) is a flavonoid compound with antioxidant and other biological activities. To investigate the protective effect of Que on Cd-induced renal apoptosis in rats. 24 male SD rats were randomly divided into four groups. They were treated as follows: control group was administered orally with normal saline (10 ml/kg); Cd group was injected with 2 mg/kg CdCl intraperitoneally; Cd + Que group was injected with 2 mg/kg CdCl and intragastric administration of Que (100 mg/kg); Que group was administered orally with Que (100 mg/kg). The experimental results showed that the body weight of Cd-exposed rats significantly decreased and the kidney coefficient increased. In addition, Cd significantly increased the contents of Blood Urea Nitrogen, Creatinine and Uric acid. Cd also increased the glutathione and malondialdehyde contents in renal tissues. The pathological section showed that Cd can cause pathological damages such as narrow lumen and renal interstitial congestion. Cd-induced apoptosis of kidney, which could activate the mRNA and protein expression levels of Cyt-c, Caspase-9 and Caspase-3 were significantly increased. Conversely, Que significantly reduces kidney damage caused by Cd. Kidney pathological damage was alleviated by Que. Que inhibited Cd-induced apoptosis and decreased Cyt-c, Caspase-9 and Caspase-3 proteins and mRNA expression levels. To sum up, Cd can induce kidney injury and apoptosis of renal cells, while Que can reduce Cd-induced kidney damage by reducing oxidative stress and inhibiting apoptosis. These results provide a theoretical basis for the clinical application of Que in the prevention and treatment of cadmium poisoning.

摘要

镉(Cd)作为一种重金属,对动物和人类健康具有有害影响,并且还能明显诱导细胞凋亡。槲皮素(Que)是一种具有抗氧化及其他生物活性的黄酮类化合物。为研究Que对镉诱导的大鼠肾细胞凋亡的保护作用。将24只雄性SD大鼠随机分为四组。它们的处理方式如下:对照组经口给予生理盐水(10 ml/kg);镉组腹腔注射2 mg/kg氯化镉;镉+槲皮素组腹腔注射2 mg/kg氯化镉并灌胃给予槲皮素(100 mg/kg);槲皮素组经口给予槲皮素(100 mg/kg)。实验结果表明,暴露于镉的大鼠体重显著下降,肾系数增加。此外,镉显著增加了血尿素氮、肌酐和尿酸的含量。镉还增加了肾组织中谷胱甘肽和丙二醛的含量。病理切片显示,镉可导致管腔狭窄和肾间质充血等病理损伤。镉诱导的肾细胞凋亡,可使细胞色素C(Cyt-c)、半胱天冬酶-9(Caspase-9)和半胱天冬酶-3(Caspase-3)的mRNA和蛋白表达水平显著升高。相反,槲皮素显著减轻了镉所致的肾损伤。槲皮素减轻了肾脏病理损伤。槲皮素抑制了镉诱导的细胞凋亡,并降低了Cyt-c、Caspase-9和Caspase-3蛋白及mRNA表达水平。综上所述,镉可诱导肾损伤和肾细胞凋亡,而槲皮素可通过减轻氧化应激和抑制细胞凋亡来减轻镉所致的肾损伤。这些结果为槲皮素在镉中毒防治中的临床应用提供了理论依据。

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