丹参酮ⅡA磺酸钠对环境细颗粒物诱导的大鼠肺部损伤的保护作用

doi:10.3969/j.issn.1004-616x.2022.01.005

癌变·畸变·突变 ›› 2022, Vol. 34 ›› Issue (1): 25-29,34.doi: 10.3969/j.issn.1004-616x.2022.01.005

丹参酮ⅡA磺酸钠对环境细颗粒物诱导的大鼠肺部损伤的保护作用

陈东亚, 陆罗定, 陈耿, 张颖, 俞萍, 吕中明, 卞倩

江苏省疾病预防控制中心毒理与风险评估研究所, 江苏南京 210009

收稿日期:2021-07-07 修回日期:2021-10-26 出版日期:2022-01-31 发布日期:2022-02-15
通讯作者: 卞倩,E-mail:bianqian@jscdc.cn E-mail:bianqian@jscdc.cn
作者简介:陈东亚,E-mail:70641911@qq.com
基金资助:
国家自然科学基金（81773479，91743205）；江苏省卫生计生委科研课题（H201634）

Protective effects of sulfotanshinone sodium on lung injury in rats induced by environmental fine particulate matters

CHEN Dongya, LU Luoding, CHEN Geng, ZHANG Ying, YU Ping, Lü Zhongming, BIAN Qian

Institute of Toxicology and Risk Assessment, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, China

Received:2021-07-07 Revised:2021-10-26 Online:2022-01-31 Published:2022-02-15

摘要/Abstract

摘要： 目的： 探讨丹参酮ⅡA磺酸钠（STS）对大气细颗粒物（PM_2.5）诱导的大鼠肺部损伤的保护作用及可能机制。方法： 24只清洁级雄性SD大鼠，随机分为4组，每组6只，分别为对照组（生理盐水）、PM_2.5染毒组（模型组）、丹参酮ⅡA磺酸钠组（STS组）、地塞米松组（阳性对照）。采用气管滴注PM_2.5悬液染毒，除对照组外，其余3组染毒剂量均为5.4 mg/kg，每3 d滴注1次，共10次，于染毒第1天起STS组和地塞米松组分别以浓度15 mg/kg和0.5 mg/kg腹腔注射，每天1次，持续28 d。末次染毒后24 h采用整体体积描记法（WBP）检测大鼠呼吸频率（f值）和被迫呼吸间隙（Penh）；末次染毒后2 d，经腹主动脉采血2 mL，流式细胞术检测外周血淋巴细胞亚群；处死大鼠后灌洗左肺，收集肺泡灌洗液5 mL，ELISA法测定肺泡灌洗液中白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素6（IL-6）含量；Western blot检测肺组织核因子κB （NF-κB）蛋白表达。结果： 与对照组相比，模型组呼吸f值和Penh值均明显升高（P<0.01）；CD4⁺细胞百分率和CD4⁺/CD8⁺比值降低（P<0.05）；肺泡灌洗液中IL-1β、TNF-α和IL-6浓度升高（P<0.01）；肺细胞浆中P65含量降低而胞核中p-P65含量升高（P<0.01）。与模型组相比，STS组f值和Penh值均降低（P<0.05或P<0.01）；CD4⁺细胞百分率和CD4⁺/CD8⁺比值均升高（P<0.01或P<0.05）；IL-1β、TNF-α、IL-6浓度降低（P<0.01或P<0.05）；细胞浆中P65含量升高而胞核中p-P65含量降低（P<0.01）。结论： STS对PM_2.5诱导的大鼠肺部炎症有抑制作用，并具有调节肺功能和免疫功能的作用。

关键词: 丹参酮ⅡA磺酸钠, PM_2.5, 肺功能, 炎症因子, NF-κB

Abstract: OBJECTIVE: To investigate protective effects of Sulfotanshinone Sodium on lung injury induced by environmental fine particulate matters(PM_2.5)in rats. METHODS: 24 clean male SD rats were randomly divided into 4 groups with 6 rats in each group:control group (normal saline),PM_2.5 group,tanshinone Ⅱ A sodium sulfonate group (STS group) and dexamethasone group (positive control). PM_2.5 suspension was administered by intratracheal instillation. Except the control group,the dose of the other three groups was 5.4mg/kg,once every three days,a total of 10 times. From the first day of exposure,the STS and dexamethasone groups were injected intraperitoneally at the concentration of 15 mg/kg and 0.5mg/kg respectively,once a day for 28 days. 24 hours after the last exposure,respiratory frequencies and enhanced pauses were measured by whole body plethysmography (WBP). Two days after the last exposure,2ml blood was collected through abdominal aorta,and the peripheral blood lymphocyte subsets were detected by flow cytometry. After the rats were killed,the left lung was lavaged,and the bronchoalveolar lavage fluid (BALF) was collected to determine the contents of interleukin-1β (IL-1β),tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) by ELISA. Western blot was used to detect the expression of NF-κB protein in lung tissue. RESULTS: Compared with the control group,the respiratory f and Penh values of the model group were significantly increased (P<0.01);the CD4⁺ and CD4⁺/CD8⁺ values were decreased (P<0.05);the IL-1β,TNF-α and IL-6 values in BALF were increased (P<0.01),and the P65 contents in the lung cytoplasm were decreased while the p-P65 contents in the nucleus were increased (P<0.01). Compared with the model group,the f and Penh values in STS group decreased (P<0.05 or P<0.01);CD4⁺ and CD4⁺/CD8⁺ in peripheral blood increased (P<0.01 or P<0.05),and the contents of IL-1β,TNF-α,IL-6 in BALF were decreased (P<0.01 or P<0.05);P65 in cytoplasm increased and p-P65 content in nucleus decreased (P<0.01). CONCLUSION: STS had protective effects on rat lung inflammation induced by PM_2.5,via regulation of lung and immune functions.

Key words: sulfotanshinone sodium, PM_2.5, lung function, inflammatory factors, NF-κB

中图分类号:

R285.5

陈东亚, 陆罗定, 陈耿, 张颖, 俞萍, 吕中明, 卞倩. 丹参酮ⅡA磺酸钠对环境细颗粒物诱导的大鼠肺部损伤的保护作用[J]. 癌变·畸变·突变, 2022, 34(1): 25-29,34.

CHEN Dongya, LU Luoding, CHEN Geng, ZHANG Ying, YU Ping, Lü Zhongming, BIAN Qian. Protective effects of sulfotanshinone sodium on lung injury in rats induced by environmental fine particulate matters[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 25-29,34.

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丹参酮ⅡA磺酸钠对环境细颗粒物诱导的大鼠肺部损伤的保护作用

Protective effects of sulfotanshinone sodium on lung injury in rats induced by environmental fine particulate matters

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