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.
维普
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