基于5-LOX/LTB4信号通路探讨PM_(2.5)对大鼠脑肾损伤的机制研究  

Mechanism of PM_(2.5)on Brain and Kidney Injury in Rats Based on 5-LOX/LTB4 Signaling Pathway

作　　者：赵安东 孙欠欠 张嘉豪 呼田 周雪薇 刘继平[1,2,3] 王川 王斌[1,2,3] ZHAO Andong;SUN Qianqian;ZHANG Jjahao;HU Tian;HOU Xuewei;LIU Jiping;WANG Chuan;WANG Bin(Shanxi University of Chinese Medicine;Shaanxi University Engineering Research Centre for TCM Brain Health Industry;Key Research Laboratory of the Mechanisms and Material Basis of Chinese Medicine Efficacy,Shaanxi Provincial Administration of Traditional Chinese Medicine,Xianyang 712046)

机构地区：[1]陕西中医药大学 [2]中医药脑健康产业陕西省高校工程研究中心 [3]陕西省中医药管理局中药药效机制与物质基础重点研究室,咸阳712046

出　　处：《中药药理与临床》2024年第11期82-86,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：中医药“双链融合”中青年科研创新团队(编号:2022-SLRH-YQ-006);国家自然科学基金资助项目(编号:81473385);陕西省中医药科研项目(编号:2021-ZZ-JC023);咸阳市重点研发科技项目(编号:JBGS-001);陕西省中医脑病学重点实验室(编号:KF202317);教育部春晖计划项目(编号:202070310)。

摘　　要：目的:“脑肾相关”理论认为,脑与肾生理相系,经络相通,阴阳互应,从“脑肾相关”理论出发,本研究旨在探讨气道吸入不同剂量PM_(2.5)混悬液是否通过激活5-LOX/LTB4通路对大鼠脑、肾组织造成损伤,为中医脑肾相关理论生物学基础和中药相关研究提供参考。方法:SD大鼠随机分为正常对照组、PM_(2.5)7.5、15、30 mg/kg染毒组,每组6只。染毒组通过气管滴注相应剂量混悬液1 mL/kg,6天滴注1次,持续3个月,正常对照组滴注等体积生理盐水,滴注期间每日记录大鼠生理状况。末次滴注完成后,禁食12 h,取材后,以肾脏组织病理切片、24 h尿量、尿常规及血清肾功能指标BUN、SCR评估肾脏功能损伤情况;以脑组织病理切片、脑血流量反应脑组织损伤情况;以血清中IL-1β、IL-6、TNF-α、IL-10、TGF-β1含量及脑、肾组织5-LOX蛋白和LTB4表达情况反应PM_(2.5)是否可引发全身炎症反应并激活5-LOX/LTB4信号通路对大鼠脑、肾组织造成炎性损伤。结果:滴注不同剂量PM_(2.5)混悬液后,模型对照组大鼠毛色均出现暗淡发黄且摄食、体质量下降等情况;与正常对照组相比,各模型对照组大鼠脑、肾组织出现不同程度的水肿、炎性细胞浸润等情况;其中PM_(2.5)15、30 mg/kg组大鼠尿量、血清BUN、SCR含量显著升高(P<0.01);各染毒组大鼠脑血流量显著下降(P<0.01);血清中IL-1β、IL-6、TNF-α含量显著升高(P<0.01);IL-10、TGF-β1显著下降(P<0.01);脑、肾组织中5-LOX、LTB4表达显著升高(P<0.01)。结论:PM_(2.5)吸入可造成脑、肾组织损伤,机制可能是由于PM_(2.5)进入机体激活5-LOX/LTB4信号通路表达,引起脑、肾的炎症反应,导致脑肾损伤。Objective:The Nao(brain)-Shen(kidney)correlation theory in traditional Chinese medicine(TCM)posits that Nao and Shen are physiologically connected,share meridians,and interact through yin-yang responses.Based on this theory,the study aimed to investigate whether inhalation of PM_(2.5)suspension at different doses caused damage to rat brain and kidney tissues through the activation of the 5-LOX/LTB4 pathway.This study also aimed to provide a biological basis for the Naoshenxiangguan theory and serve as a reference for experimental and clinical studies of related TCM drugs.Methods:SD rats were randomly divided into a normal control group and PM_(2.5)exposure groups at doses of 7.5,15,and 30 mg/kg,with 6 rats in each group.The rats in the exposure groups were treated with the corresponding dose of PM_(2.5)suspension(1 mL/kg)via tracheal instillation once every 6 days for 3 months,while the control group received an equivalent volume of saline during the same period.The physiological conditions of the rats were recorded daily during the instillation period.After the final instillation,the rats were fasted for 12 hours before tissue collection.Renal histopathological section,24-hour urine volume,urine routine and serum renal function indexes BUN,SCR were employed to assess renal function impairment.Brain histopathological section and brain blood flow were used to assess the pathological damage in brain tissue.The expression levels of IL-1β,IL-6,TNF-α,IL-10 and TGF-β1 in the serum and the protein expressions of 5-LOX and LTB4 in brain and kidney tissues were were analyzed to determine whether PM_(2.5)could induce systemic inflammation and activate the 5-LOX/LTB4 signaling pathway to cause inflammatory injury to rat brain and kidney tissues.Results:After intratracheal instillation of different doses of PM_(2.5)suspension,rats in the model group,rats in the model groups showed dull and yellowish fur color,decreased food intake,and reduced body weight.Compared with the control group,rats in each PM_(2.5)exposure group

关 键 词：PM_(2.5) 5-脂氧合酶 白三烯B4 脑肾损伤 炎性损伤 

分 类 号：R28[医药卫生—中药学]