右美托咪定抑制NOX4缓解急性应激致大鼠肾损伤

doi:10.11843/j.issn.0366-6964.2023.02.034

畜牧兽医学报 ›› 2023, Vol. 54 ›› Issue (2): 779-786.doi: 10.11843/j.issn.0366-6964.2023.02.034

右美托咪定抑制NOX4缓解急性应激致大鼠肾损伤

杨昊天¹, 陈永平², 王志强¹, 黄宇翔¹, 马志刚¹, 邹跃¹, 魏念冬¹, 张红¹, 李鑫¹, 董佳强¹, 吕明哲¹, 李洪彬¹, 刘力威¹, 杨昊轩³, 张国华¹, 刘雪松¹, 钟鹏¹, 石荷叶⁴, 寇玉红⁵, 陈志峰^1*

1. 黑龙江省农业科学院畜牧兽医分院, 齐齐哈尔 161005;
2. 青岛农业大学动物医学学院, 青岛 266109;
3. 内蒙古自治区扎兰屯市高台子党群服务中心, 扎兰屯 162650;
4. 大庆市杜尔伯特蒙古族自治县畜牧技术服务中心, 大庆 166200;
5. 黑龙江省农业科学院大豆研究所, 哈尔滨 150086

收稿日期:2022-08-01 出版日期:2023-02-23 发布日期:2023-02-21
通讯作者: 陈志峰,主要从事营养与繁殖研究,E-mail:qqhr139@sina.com
作者简介:杨昊天(1995-),男,黑龙江齐齐哈尔人,实习研究员,硕士,主要从事家禽疾病研究,E-mail:954161803@qq.com
基金资助:
现代农业产业技术体系建设专项资金（CARS-42-34）；国家自然科学基金（31902337）；黑龙江省农业科学院畜牧兽医分院自拟课题

Dexmedetomidine Inhibits NOX4 and Alleviates Acute Stress-induced Renal Injury in Rats

YANG Haotian¹, CHEN Yongping², WANG Zhiqiang¹, HUANG Yuxiang¹, MA Zhigang¹, ZOU Yue¹, WEI Niandong¹, ZHANG Hong¹, LI Xin¹, DONG Jiaqiang¹, Lü Mingzhe¹, LI Hongbin¹, LIU Liwei¹, YANG Haoxuan³, ZHANG Guohua¹, LIU Xuesong¹, ZHONG Peng¹, SHI Heye⁴, KOU Yuhong⁵, CHEN Zhifeng^1*

1. Animal Husbandry and Veterinary Branch of Heilongjiang Academy of Agricultural Sciences, Qiqihaer 161005, China;
2. College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, China;
3. Party Service Center in Gaotaizi, Zhalantun City, Inner Mongolia Autonomous Region, Zhalantun 162650, China;
4. Daqing Dulbert Mongol Autonomous County Animal Husbandry Technology Service Center, Daqing 166200, China;
5. Soybean Research Institute, Heilongjiang Academy of Agricultural Sciences, Harbin 150086, China

Received:2022-08-01 Online:2023-02-23 Published:2023-02-21

摘要/Abstract

摘要： 本研究拟探索右美托咪定（dexmedetomidine，DEX）对大鼠急性应激致肾损伤的保护作用，并从氧化应激的角度探索DEX对大鼠肾的保护通路。本研究使用了急性束缚应激模型，其中，大鼠被迫游泳15 min，并束缚3 h。本试验采用生化检测、组织病理学切片观察以评估肾功能，然后测定了氧化应激以及氧化应激的相关通路蛋白。旷场试验证实成功建立了急性应激模型。急性应激引起的肾损伤增加了NOX4，降低了Nrf2/HO-1/NQO1表达水平。DEX可降低NOX4表达，同时升高Nrf2/HO-1/NQO1的表达水平。DEX治疗组与急性应激组相比的肾生化结果明显恢复正常，病理切片观察损伤显著降低。试验结果表明，DEX治疗急性应激可影响NOX4/Nrf2/HO-1/NQO1信号通路，并抑制氧化应激。因此，DEX对急性应激引起的肾损伤具有保护作用，并在应激综合征中具有潜在的临床应用。

关键词: 急性应激, 氧化应激, 肾损伤, 右美托咪定, NOX4

Abstract: This study was conducted to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and to explore the protective pathways of DEX on rat kidney from the perspective of oxidative stress. In this study, an acute restraint stress model was used, in which rats were forced to swim for 15 minutes and restrained for 3 hours. This experiment was performed with biochemical assays, histopathological section observation to assess renal function, followed by determination of oxidative stress and proteins of pathways related to oxidative stress. The open-field experiments confirmed that the acute stress model had been successfully established. DEX decreased NOX4 expression and increased Nrf2/HO-1/NQO1 expression, and the kidney biochemical results were significantly normalized in the DEX-treated group compared with the acute stress group, and the damage was significantly reduced in the pathological sections. The experimental results suggest that DEX treatment of acute stress can affect NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress. Therefore, DEX has a protective effect on acute stress-induced renal injury and has potential clinical applications in stress syndromes.

Key words: acute stress, oxidative stress, kidney injury, dexmedetomidine, NOX4

中图分类号:

S856.59

杨昊天, 陈永平, 王志强, 黄宇翔, 马志刚, 邹跃, 魏念冬, 张红, 李鑫, 董佳强, 吕明哲, 李洪彬, 刘力威, 杨昊轩, 张国华, 刘雪松, 钟鹏, 石荷叶, 寇玉红, 陈志峰. 右美托咪定抑制NOX4缓解急性应激致大鼠肾损伤[J]. 畜牧兽医学报, 2023, 54(2): 779-786.

YANG Haotian, CHEN Yongping, WANG Zhiqiang, HUANG Yuxiang, MA Zhigang, ZOU Yue, WEI Niandong, ZHANG Hong, LI Xin, DONG Jiaqiang, LÜ Mingzhe, LI Hongbin, LIU Liwei, YANG Haoxuan, ZHANG Guohua, LIU Xuesong, ZHONG Peng, SHI Heye, KOU Yuhong, CHEN Zhifeng. Dexmedetomidine Inhibits NOX4 and Alleviates Acute Stress-induced Renal Injury in Rats[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(2): 779-786.

参考文献 28

[1]	ROSENBERGER C, ELSENBRUCH S, SCHOLLE A, et al. Effects of psychological stress on the cerebral processing of visceral stimuli in healthy women[J]. Neurogastroenterol Motil, 2009, 21(7):740-e45.
[2]	MCEWEN B S, GIANAROS P J. Stress- and allostasis-induced brain plasticity[J]. Annu Rev Med, 2011, 62:431-445.
[3]	SMEETS T, JELICIC M, MERCKELBACH H. The effect of acute stress on memory depends on word valence[J]. Int J Psychophysiol, 2006, 62(1):30-37.
[4]	SCHOOFS D, PREUSS D, WOLF O T. Psychosocial stress induces working memory impairments in an n-back paradigm[J]. Psychoneuroendocrinology, 2008, 33(5):643-653.
[5]	STOJANOVICH L, MARISAVLJEVICH D. Stress as a trigger of autoimmune disease[J]. Autoimmun Rev, 2008, 7(3):209-213.
[6]	BROWN S M, HENNING S, WELLMAN C L. Mild, short-term stress alters dendritic morphology in rat medial prefrontal cortex[J]. Cereb Cortex, 2005, 15(11):1714-1722.
[7]	BLACK P H, GARBUTT L D. Stress, inflammation and cardiovascular disease[J]. J Psychosom Res, 2002, 52(1):1-23.
[8]	ROSENGREN A, HAWKEN S, ÕUNPUU S, et al. Association of psychosocial risk factors with risk of acute myocardial infarction in 11 119 cases and 13 648 controls from 52 countries (the INTERHEART study):case-control study[J]. Lancet, 2004, 364(9438):953-962.
[9]	MACDONALD J J, ROBERTS J C, WASHINGTON S. Stress ulcer prophylaxis:friend or foe?[J]. Br J Hosp Med (Lond), 2012, 73(4):238-238.
[10]	ZHU Q, GU L W, WANG Y M, et al. The role of alpha-1 and alpha-2 adrenoceptors in restraint stress-induced liver injury in mice[J]. PLoS One, 2014, 9(3):e92125.
[11]	WOHLAUER M V, SAUAIA A, MOORE E E, et al. Acute kidney injury and posttrauma multiple organ failure:the canary in the coal mine[J]. J Trauma Acute Care Surg, 2012, 72(2):373-380.
[12]	WANG Y B, YAN J L, XI L, et al. Protective effect of crocetin on hemorrhagic shock-induced acute renal failure in rats[J]. Shock, 2012, 38(1):63-67.
[13]	AMIN S N, EL-AIDI A A, ZICKRI M B, et al. Hepatoprotective effect of blocking N-methyl-D-aspartate receptors in male albino rats exposed to acute and repeated restraint stress[J]. Can J Physiol Pharmacol, 2017, 95(6):721-731.
[14]	LEE J S, KIM H G, LEE H W, et al. Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model[J]. J Ethnopharmacol, 2017, 207:226-236.
[15]	MA J Q, LIU C M, YANG W. Protective effect of rutin against carbon tetrachloride-induced oxidative stress, inflammation and apoptosis in mouse kidney associated with the ceramide, MAPKs, p53 and calpain activities[J]. Chem Biol Interact, 2018, 286:26-33.
[16]	陈永平. 右美托咪定通过调控NE/ROS/JNK对急性应激致大鼠肾损伤保护作用[D]. 哈尔滨:东北农业大学, 2019.CHEN Y P. Protective effect of dexmedetomidine on acute stress-induced kidney injury in rats by regulating NE/ROS/JNK[D]. Harbin:Northeast Agricultural University, 2019. (in Chinese)
[17]	杨昊天. 基于P2X7R/NF-κB/NLRP3通路探究右美托咪定对急性应激致大鼠肾损伤的保护作用机制[D]. 哈尔滨:东北农业大学, 2021.YANG H T. Protective mechanism of dexmedetomidine on acute stress induced renal injury in rats via the regulation of P2X7R/NF-κB/NLRP3 pathway[D]. Harbin:Northeast Agricultural University, 2021. (in Chinese)
[18]	CHEN Y P, YANG H T, YANG T Y, et al. Protective effects of low-dose alcohol against acute stress-induced renal injury in rats:involvement of CYP4A/20-HETE and LTB4/BLT1 pathways[J]. Oxid Med Cell Longev, 2021, 2021:4475968.
[19]	SHA J C, FENG X J, CHEN Y P, et al. Dexmedetomidine improves acute stress-induced liver injury in rats by regulating MKP-1, inhibiting NF-κB pathway and cell apoptosis[J]. J Cell Physiol, 2019, 234(8):14068-14078.
[20]	TOMA V A, FARCAS A D, PARVU M, et al. CA3 hippocampal field:cellular changes and its relation with blood nitro-oxidative stress reveal a balancing function of CA3 area in rats exposed to repetead restraint stress[J]. Brain Res Bull, 2017, 130:10-17.
[21]	RATLIFF B B, ABDULMAHDI W, PAWAR R, et al. Oxidant mechanisms in renal injury and disease[J]. Antioxid Redox Signal, 2016, 25(3):119-146.
[22]	LIN L, CUI F Y, ZHANG J J, et al. Antioxidative and renoprotective effects of residue polysaccharides from Flammulina velutipes[J]. Carbohydr Polym, 2016, 146:388-395.
[23]	邹万忠. 肾活检病理学[M]. 2版. 北京:北京大学医学出版社, 2009.ZOU W Z. Pathology of renal biopsy[M]. 2nd ed. Beijing:Peking University Medical Press, 2009. (in Chinese)
[24]	宣吉晴, 李明星, 陈晓梅, 等. 兔肾缺血-再灌注损伤后叶间动脉血流动力学变化与肾小管上皮Bcl-2表达的相关性[J]. 中国医学影像学杂志, 2012, 20(3):212-215, 219.XUAN J Q, LI M X, CHEN X M, et al. The correlation between hemodynamic change of the renal interlobar arteria and the expression of Bcl-2 Protein in tubular epithelial cells on rabbit renal ischemia reperfusion models[J]. Chinese Journal of Medical Imaging, 2012, 20(3):212-215, 219. (in Chinese)
[25]	OLFE J, DOMANSKA G, SCHUETT C, et al. Different stress-related phenotypes of BALB/c mice from in-house or vendor:alterations of the sympathetic and HPA axis responsiveness[J]. BMC Physiol, 2010, 10:2.
[26]	CHEN Y P, FENG X J, HU X Y, et al. Dexmedetomidine ameliorates acute stress-induced kidney injury by attenuating oxidative stress and apoptosis through inhibition of the ROS/JNK signaling pathway[J]. Oxid Med Cell Longev, 2018, 2018:4035310.
[27]	TARAFDAR A, PULA G. The role of NADPH oxidases and oxidative stress in neurodegenerative disorders[J]. Int J Mol Sci, 2018, 19(12):3824.
[28]	韩勇, 郭立荣, 贺滟, 等. 20-HETE对大鼠心肌缺血再灌注损伤中NADPH氧化酶活性及ROS生成的影响[J]. 遵义医学院学报, 2016, 39(4):366-371.HAN Y, GUO L R, HE Y, et al. Effect of 20-HETE on NADPH oxidase activity and ROS production of rats with myocardial ischemia reperfusion injury[J]. Journal of Zunyi Medical University, 2016, 39(4):366-371. (in Chinese)

右美托咪定抑制NOX4缓解急性应激致大鼠肾损伤

Dexmedetomidine Inhibits NOX4 and Alleviates Acute Stress-induced Renal Injury in Rats

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