首页|尼古丁上调Cx43促发PASMCs炎性反应致小鼠肺动脉重构的机制

尼古丁上调Cx43促发PASMCs炎性反应致小鼠肺动脉重构的机制

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目的 研究缝隙连接蛋白43(connexin43,Cx43)介导肺动脉平滑肌细胞(pulmonary artery smooth muscle cells,PASMCs)炎性反应在尼古丁致小鼠肺动脉重构中的作用机制.方法 5周龄雄性C57BL/6J小鼠、Tagln-Cre(+);Cx43flox/WT小鼠各32只,分别随机分为对照组(灭菌注射水)、0.02、0.2和2.0mg/(kg·d)尼古丁组,每组8只.小鼠按体重每天固定时间进行一次鼻腔滴注,持续8周.染毒结束后,通过HE染色观察各组小鼠肺动脉重构情况;采用磁性分离法培养C57BL/6J、Tagln-Cre(+);Cx43flox/WT 小鼠原代远端 PASMCs;通过 Western blot 法检测小鼠 PASMCs 中 Cx43、肿瘤坏死因子-α(tumor nec-rosis factor-alpha,TNF-α)、白细胞介素-lβ(interleukin 1β,IL-1β)和白细胞介素-6(interleukin 6,IL-6)蛋白表达水平.结果 与C57BL/6J小鼠对照组相比,尼古丁染毒组C57BL/6J小鼠体重总体呈现增长趋势,且随着尼古丁浓度增加,体重增长变缓.小鼠远端肺动脉出现管壁增厚、管腔狭窄等典型的动脉重构病理特征,Cx43表达上调且呈剂量依赖性关系.Tagln-Cre(+);Cx43flox/WT小鼠HE染色结果显示其肺动脉管壁增厚和管腔狭窄现象有所缓解,且PASMCs中上述炎性反应因子表达减少.结论 Cx43表达下调可缓解尼古丁诱导的小鼠远端PASMCs炎性反应,从而改善小鼠肺动脉重构.
Mechanism of nicotine inducing pulmonary arterial remodeling through upregulating connexin 43 to promote inflammatory response in PASMCs in mice
Objective To investigate the mechanism of the gap junction protein connexin 43(Cx43)mediating the inflammatory re-sponse of pulmonary artery smooth muscle cells(PASMCs)in nicotine-induced pulmonary artery remodeling in mice.Methods Thirty-two 5-week-old male C57BL/6J mice and Tagln-Cre(+);Cx43flox/WT mice each were randomly divided into control group(sterile water for injection),0.02 mg/(kg·d)nicotine group,0.2 mg/(kg·d)nicotine,and 2.0 mg/(kg·d)nicotine group,with 8 mice in each group.The mice were treated through nasal drip according to body weight,once a day at a fixed time for continuous 8 weeks.After expo-sure,the mice were examined for pulmonary arterial remodeling with hematoxylin-eosin(HE)staining.The primary distal PASMCs of C57BL/6J mice and Tagln-Cre(+);Cx43flox/W 1 mice were cultured by magnetic separation.The protein expression levels of Cx43,tumor necrosis factor-alpha,interleukin-1 β,and interleukin-6 in mouse PASMCs were measured by Western blot.Results Compared with C57BL/6J mice in the control group,C57BL/6J mice in the nicotine groups showed a generally increasing trend in body weight,and the body weight growth slowed down with the increase in nicotine concentrations;the distal pulmonary arteries showed typical pathological fea-tures of arterial remodeling including wall thickening and lumen narrowing;and the expression of Cx43 was up-regulated in a dose-de-pendent manner.Tagln-Cre(+);HE staining results of Cx43flox/WT mice showed milder wall thickening and lumen narrowing of pulmonary arteries and lower expression levels of the inflammatory factors in PASMCs.Conclusion Downregulating Cx43 can alleviate nicotine-in-duced inflammatory responses in distal PASMCs,thereby improving pulmonary arterial remodeling in mice.

nicotineconnexin 43pulmonary arterial remodelingmouse primary pulmonary artery smooth muscle cellinflam-matory response

赵旭、侯晓敏、孙琳、徐祎、董霖、江雪露、饶国娇、邹佳佳、施熠炜、秦小江

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山西医科大学公共卫生学院,太原 030001

山西医科大学基础医学院

环境暴露血管疾病研究所,山西医科大学

山西医科大学医学科学院

山西医科大学第一医院

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尼古丁 连接蛋白43 肺动脉重构 小鼠原代肺动脉平滑肌细胞 炎性反应

国家自然科学基金面上项目国家自然科学基金青年基金项目国家卫生健康委员会尘肺病重点实验室开放课题山西省科技创新人才团队专项项目山西省留学人员科技活动择优资助项目重点项目山西省科技合作交流专项项目中央级公益性科研院所科研业务项目

8237362282204042YKFKT006ANHC202307202304051001038202200192022040411010222020-PT320-005

2024

10.13421/j.cnki.hjwsxzz.2024.09.010

环境卫生学杂志
中国疾病预防控制中心

环境卫生学杂志

CSTPCD
影响因子：0.735
ISSN：2095-1906
年,卷(期)：2024.14(9)