Effect of smoking cessation on expression of pulmonary vascular connective tissue growth factor and matrix metalloproteinase-2 in rats of cigarette smoke exposure

Abstract

Objective To observe the effect of smoking cessation on expression of pulmonary vascular connective tissue growth factor (CTGF) and matrix metalloproteinase-2 (MMP-2) in rats which exposed cigarette smoke and to probe the roles of CTGF and MMP-2 in pulmonary vascular remodeling.Methods Forty male SD rats were randomly divided into control group (C group),smoke exposure four weeks group (S1 group),smoke exposure four weeks and smoke cessation four weeks group (Q1 group),smoke exposure 12 weeks group (S2 group),smoke exposure 12 weeks and smoke cessation four weeks group (Q2 group),with eight rats in each group.The ratio of pulmonary vascular wall thickness/vascular external diameter (WT％) and the ratio of pulmonary vascular wall area/ total pulmonary vascular area (WA％) were measured by image analysis system.The expressions of CTGF and MMP-2 protein in pulmonary vascular of each group were evaluated by immunohistochemistry.The expressions of CTGF and MMP-2 mRNA in pulmonary vascular of each group were detected by reverse transcriptionpolymerase chain reaction.Results ①WT％ and WA％ in S1 group [(42.48± 6.17)％00,(62.21 ± 5.79) ％] and S2 group [(51.84 ± 8.88)％,(74.09 ± 10.51) ％] were higher than those in C group [(30.21± 8.51) ％,(48.82 ± 10.78) ％],WT％ and WA％ in S2 group were higher than those in S1 group (allP ＜0.05).WT％ and WA％ in Q1 group [(31.86±5.74) ％,(50.76± 11.15) ％] were lower than those in S1 group,WT％ and WA％ in Q2 group [(40.54± 11.87) ％,(63.39± 10.95) ％] were lower than those in S2 group,but higher than those in Q1 group and C group (all P ＜0.05).There was no statistical difference in WT％ and WA％ between Q1 group and C group (P ＞ 0.05).② The expressions of CTGF protein and mRNA in S1 group (0.269 ± 0.041,1.725 ± 0.529) and S2 group (0.388±0.034,2.541±0.945) were higher than those in C group (0.204±0.046,0.716±0.439),the expressions of CTGF protein and mRNA in S2 group were higher than those in S1 group (all P ＜0.05).The expressions of CTGF protein and mRNA in Q1 group (0.225±0.036,1.018±0.571) were lower than those in S1 group,the expressions of CTGF protein and mRNA in Q2 group (0.303 ± 0.039,1.903 ± 0.881) were lower than those in S2 group,but higher than those in Q1 group and C group (all P ＜0.05).There was no statistical difference in the expressions of CTGF protein and mRNA between Q1 group and Cgroup (P＞0.05).③ The expressions of MMP 2 protein and mRNA in S1 group (0.388±0.041,1.167 ± 0.639) and S2 group (0.578 ± 0.387,3.721 ± 0.825) were higher than those in C group (0.190 ± 0.022,0.276±0.256),the expressions of MMP 2 protein and mRNA in S2 group were higher than those in S1 group (all P ＜0.05).The expressions of MMP-2 protein and mRNA in Q1 group (0.202±0.036,0.548±0.297) were lower than those in S1 group (all P ＜0.05).The expressions of MMP-2 protein and mRNA in Q2 group (0.395±0.039,2.934±0.683) were lower than those in S2 group,but higher than those in Q1 group and C group (all P ＜0.05).There was no statistical difference in the expressions of MMP 2 protein and mRNA between Q1 group and C group (P ＞0.05).④The protein of CTGF was positively correlated with mRNA of CTGF and the protein of MMP-2 was positively correlated with mRNA of MMP-2 (r =0.816,0.663,all P ＜0.05).The protein of CTGF was positively correlated with the protein of MMP-2 (r =0.608,P ＜ 0.05).The proteins of CTGF and MMP 2 in pulmonary vascular were positively correlated with WT％ and WA％ (r =0.627 ～ 0.690,all P ＜ 0.05).Conclusions Smoke cessation can reduce pulmonary vascular remodeling of rats exposed in cigarette smoke. Key words: Cigarette smoke exposure; Pulmonary vascular; Remodeling; Connective tissue growth factor; Matrix metalloproteinase-2