百草枯中毒大鼠肺组织中KL-6黏糖蛋白和羟脯胺酸的表达及肺纤维化的变化

Expression of KL-6 mucoprotein and hydroxyproline in lung tissue and changes of pulmonary fibrosis in paraquat-poisoned rats

目的观察百草枯中毒大鼠肺组织中涎液化糖链抗原-6(KL-6)黏糖蛋白和羟脯胺酸的表达及肺纤维化的变化。方法 54只SPF级雄性Wistar大鼠随机分为对照组(n=27)和百草枯模型组(n=27)。百草枯模型组以百草枯溶液(0. 4%)大鼠腹腔注射(14 mg/kg,单次注射)制作肺纤维化模型,对照组大鼠腹腔注射等量的生理盐水;于建模成功后第7,14,28天,每组9只大鼠,测量大鼠的体质量、颈椎脱臼处死,取肺组织计算肺系数,观察大鼠肺组织学变化,测定大鼠肺组织羟脯氨酸、超氧化物歧化酶(SOD)、丙二醛(MDA)及KL-6黏糖蛋白的表达。结果对照组大鼠在各时间点体质量增加、精神状况较好,而百草枯模型组大鼠的体质量从给药后第14天起下降,在第28天时开始回升,与同期对照组比较差异有统计学意义(P<0. 05)。百草枯模型组大鼠随着染毒时间延长,肺系数增加,在第14天时达到最大值,第28天肺系数开始降低;肺组织羟脯氨酸含量增多;羟脯氨酸含量和肺系数与同期对照组比较有统计学意义(P <0. 05)。百草枯模型组大鼠肺组织中SOD的活性增加,第28天时SOD含量表达最强(P <0. 05);肺组织中MDA含量降低,第28天时其含量表达最低(P <0. 05);肺组织中KL-6表达增加,第28天时表达最强(P <0. 05)。结论百草枯中毒大鼠肺组织中KL-6黏糖蛋白和羟脯胺酸的表达上调,且氧化应激加重。KL-6黏糖蛋白可能是百草枯引发肺纤维化的标志物。

Objective To investigate the expression of KL-6 mucoprotein and hydroxyproline in lung tissue and changes of pulmonary fibrosis of paraquat-poisoned rats.Methods Fifty-four SPF male Wistar rats were randomly divided into control group(n=27)and paraquat model group(n=27).In paraquat model group,the rats were intraperitoneally injected with 0.4%paraquat solution(14 mg/kg,single injection)to induce pulmonary fibrosis model.The rats in control group were intraperitoneally injected with the same amount of saline.At day 7,14 and 28 after successful modeling,9 rats in each group were executed by cervical spine dislocation,and the body mass of rats was measured.Lung tissue was taken to calculate the lung coefficient.The histological changes of lung were observed.The expression levels of hydroxyproline,superoxide dismutase(SOD),malondialdehyde(MDA)and KL-6 mucoprotein in lung tissues were determined.Results The body mass of rats in control group increased at different time points and their mental status was better at each time point,while the body mass in paraquat model group decreased from day14 after administration and began to rise at day 28,which was significantly different from that of control group at the same time(P<0.05).In paraquat model group,the lung coefficient increased with the prolongation of exposure time,peaked at day14,and began to decrease at day 28.The content of hydroxyproline in lung tissue increased in paraquat model group,and the content of hydroxyproline and lung coefficient showed statistically different from that of control group at the same time(P<0.05).In paraquat model group,SOD activity increased,SOD content was the highest at day 28(P<0.05),MDA content was the lowest at day 28(P<0.05),and KL-6 expression was the highest at day 28(P<0.05).Conclusion The expression of KL-6 mucoprotein and hydroxyproline in lung tissue of paraquat poisoned rats is up-regulated,and oxidative stress is aggravated.KL-6 mucoprotein may be a marker of paraquat-induced pulmonary fibrosis.