硫氧环蛋白过氧化物酶1对矽肺大鼠肺纤维化的影响

目的 探讨硫氧环蛋白过氧化物酶1(Prx-1)对矽肺大鼠肺组织纤维化的影响.方法 健康成年雄性SD大鼠按抽签法随机分为4组:对照组(生理盐水)、SiO2组(50 mg/只)、SiO2+空慢病毒组(空慢病毒滴度5×107 TU)和SiO2+-Prx-1慢病毒组(Prx-1慢病毒滴度5×107 TU),每组10只.气管内注入SiO2和慢病毒,造模后饲养4周.HE染色观察肺组织形态学变化、免疫组化法检测α-SMA表达,Western blot法检测肺组织Prx-1及Ⅰ和Ⅲ型胶原水平、硫代巴比妥酸法检测丙二醛(MDA)水平.结果 ① SiO2+Prx-1慢病毒组的Prx-1蛋白表达明显高于SiO2+空慢病毒组,差异有统计学意义(P<0.05);② 对照组大鼠肺组织结构基本正常;SiO2组和SiO2+空慢病毒组大鼠肺泡壁增厚或断裂,细胞性矽结节形成;但SiO2+Prx-1慢病毒组大鼠肺泡壁变薄,矽结节体积减小;③ 与对照组比较,SiO2组α-SMA、Ⅰ型胶原蛋白 、Ⅲ型胶原蛋白及MDA表达水平均明显增加,差异有统计学意义(P<0.05).SiO2+空慢病毒组的α-SMA、Ⅰ和Ⅲ型胶原蛋白及MDA表达水平与SiO2组无明显区别;但与SiO2+空慢病毒组比较,SiO2+Prx-1慢病毒组的α-SMA、Ⅰ型胶原蛋白 、Ⅲ型胶原蛋白及MDA表达水平明显下降,差异有统计学意义(P<0.05).结论 Prx-1能够抑制SiO2诱导的肺组织纤维化,这一作用与降低ROS、抑制肌成纤维细胞分化有关.

Effects of peroxredoxin-1 on pulmonary fibrosis in silicotic rats

Objective To study the effect of peroxredoxin-1(Prx-1) on SiO2-induced pulmonary fibrosis in rats.Methods Healthy adult male SD rats were divided into four groups randomly:control(saline,n=10),SiO2 group(50 mg/rat,n=10),SiO2+empty lentivirus group(empty lentivirus:5×107 TU,n=10) and SiO2+Prx-1 lentivirus group(Prx-1 lentivirus:5×107 TU,n=10).SiO2 and lentivirus were given by tracheal injection and then all animals were observed for four weeks.HE staining was used to observe pulmonary morphological changes and immunohistochemical staining was used to detect α-SMA expression.Western blot was used to measure expressions of Prx-1, collagen type Ⅰ and Ⅲ,and thiobarbituric acid assay was used to detect malondialdehyde(MDA) content.Results The expression of Prx-1 protein in SiO2+Prx-1 lentivirus group was significantly higher than that in SiO2+empty lentivirus group(0.45±0.05)vs(0.35±0.05),P<0.05].HE staining showed that the structure of the lung tissue of the control group was normal, and the alveolar wall was thin.There were lung tissue structural damage, alveolar wall thickening or fracture, and the formation of cellular silicon nodules in SiO2 group and SiO2+empty lentivirus group.However, the alveolar wall became thinner and the size of silicon nodules became smaller in SiO2+Prx-1 lentivirus group.Compared with control, expressions of α-SMA, collagen type I and III, and MDA content in SiO2 group significantly increased(0.40±0.16)vs(6.60±0.70),(0.34±0.05)vs(0.45±0.05),(0.18±0.03)vs(0.34±0.06) and(2.31±0.35)vs(3.46±0.44),P<0.05].There were no differences in the levels of α-SMA, collagen type Ⅰ and Ⅲ, and MDA content between SiO2 group and SiO2+lentivirus group.Compared with SiO2+empty lentivirus group, levels of α-SMA, collagen type Ⅰ and Ⅲ, and MDA content in SiO2+Prx-1 lentivirus group markedly decreased(6.00±0.58)vs2.30±0.40),(0.42±0.06)vs(0.38±0.06),(0.36±0.07)vs(0.23±0.04) and (3.57±0.62)vs(2.84±0.30),P<0.05].Conclusion Prx-1 can inhibit the pulmonary fibrosis induced by SiO2, which is related to the decrease of ROS and the differentiation of myofibroblasts.