负氧离子通过抑制氧化应激和TGF-β/Smad通路减轻尼古丁诱导的自发性高血压大鼠肾损伤。

Negative air ions alleviate nicotine-induced renal damage of spontaneously hypertensive rats via inhibiting oxidative stress and TGF-β/Smad pathway.

作者信息

Xiao Sha, Wei Tianjing, Xiao Mingyang, An Ziqi, Shan Mingming, Luo Ziyue, Zhou Jing, Li Na, Lu Xiaobo

机构信息

Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, PR China; Department of Toxicology, School of Public Health, China Medical University, Shenyang 110122, PR China; School of Public Health, Heinz Mehlhorn Academician Workstation, Hainan Medical University, Haikou 571199, PR China.

出版信息

Ecotoxicol Environ Saf. 2025 Feb;291:117882. doi: 10.1016/j.ecoenv.2025.117882. Epub 2025 Feb 16.

DOI:10.1016/j.ecoenv.2025.117882

PMID:39955865

Abstract

BACKGROUND

Nicotine can lead to renal damage in hypertension patients. Negative air ions (NAIs) is a natural antioxidant. However, rare research focus on the effect of NAIs on nicotine aggravated oxidative damage and hypertensive kidney damage.

METHODS

We used a spontaneously hypertensive rat (SHR) model to investigate the molecular mechanisms for nicotine-exacerbated renal damage and the intervention effect of NAIs. 8-week-old male rats were injected with nicotine or nicotine+ 6 h/d 4.5 × 10 to 5 × 10 NAIs/cm for 1 month or 3 months, and continuous observation of systolic blood pressure (SBP). Urine and blood were collected for test kidney injury, inflammation and oxidative stress levels, and renal tissues were harvested for pathology analysis and further molecular assays using RT-qPCR, Western blot, and immunohistochemistry.

RESULTS

Our results showed that nicotine exacerbated SBP and renal damage, and elevated serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in SHR. After 3 months of 1.5 mg/kg nicotine exposure, serum levels of urea nitrogen (BUN) and transforming growth factor beta 1 (TGF-β) in SHR increased by 1.3 times and 16.3 times, respectively. In addition, oxidative damage was significantly increased along with the activation of TGF-β/Smad pathway and promotion of epithelial mesenchymal transition (EMT), key factors reflected in the higher expression of NADPH oxidase (NOX2), α-SMA and N-cadherin proteins and increased mRNA levels of fibronectin-1 (FN1) and Twist. After NAIs intervention, levels of BUN, urinary creatinine ratio, TGF-β, endothelin 1 (ET-1) and malondialdehyde (MDA) were decreased close to SHR without nicotine exposure, and we also observed oxidative damage was significantly decreased and TGF-β/Smad pathway and EMT related factors were significantly down-regulated.

CONCLUSIONS

NAIs can attenuated nicotine-exacerbated hypertensive renal damage and fibrosis process through inhibiting oxidative stress and TGF-β/Smad pathway. We suggest that NAIs intervention could be proposed a new approach to adjuvant therapy of chronic kidney disease in smokers with hypertension.

摘要

背景

尼古丁可导致高血压患者肾脏损伤。空气负离子（NAIs）是一种天然抗氧化剂。然而，很少有研究关注空气负离子对尼古丁加重的氧化损伤和高血压性肾损伤的影响。

方法

我们使用自发性高血压大鼠（SHR）模型来研究尼古丁加重肾损伤的分子机制以及空气负离子的干预作用。8周龄雄性大鼠注射尼古丁或尼古丁+4.5×10至5×10个空气负离子/平方厘米，每天6小时，持续1个月或3个月，并持续观察收缩压（SBP）。收集尿液和血液检测肾脏损伤、炎症和氧化应激水平，并采集肾组织进行病理分析以及使用RT-qPCR、蛋白质免疫印迹法和免疫组织化学进行进一步的分子检测。

结果

我们的结果表明，尼古丁加重了SHR的收缩压和肾损伤，并提高了血清白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平。在1.5mg/kg尼古丁暴露3个月后，SHR血清尿素氮（BUN）和转化生长因子β1（TGF-β）水平分别增加了1.3倍和16.3倍。此外，氧化损伤显著增加，同时TGF-β/Smad信号通路激活，上皮-间质转化（EMT）进程加快，关键因素表现为烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX2）、α-平滑肌肌动蛋白（α-SMA）和N-钙黏蛋白蛋白表达增加，以及纤连蛋白-1（FN1）和Twist的mRNA水平升高。空气负离子干预后，BUN、尿肌酐比值、TGF-β、内皮素1（ET-1）和丙二醛（MDA）水平降低至接近未暴露于尼古丁的SHR水平，我们还观察到氧化损伤显著降低，TGF-β/Smad信号通路和EMT相关因子显著下调。