果王素通过下调转化生长因子-β1表达抑制大鼠肺纤维化

Kiwi fruit essence inhibits pulmonary fibrosis in rats by down-regulating transforming growth factor-β1

目的:通过观察果王素对博莱霉素诱导的肺纤维化(PF)大鼠肺组织转化生长因子-β1(TGF-β1)蛋白及mRNA表达的影响,探讨果王素是否可通过调节TGF-β1抑制PF,并探究其给药浓度对大鼠PF的影响。方法:将128只SD大鼠随机分为空白组、模型组、泼尼松组、果王素低、中、高剂量组(60、120、180 mg/kg),通过向气管内注入博莱霉素建立大鼠PF模型。自造模后第2天起将泼尼松及果王素按一定配比分别予以各组大鼠灌胃,空白组和模型组每日予以等量0.9%氯化钠溶液灌胃,1次/d。空白组大鼠全部于第28天处死,余组分别于第7、14、28天各处死8只并取材,通过HE、Masson染色观察大鼠肺组织病理变化,采用免疫组化、Western blot、实时荧光定量PCR检测TGF-β1蛋白及mRNA表达。结果:果王素对PF有抑制作用,并与剂量相关,空白组大鼠肺组织TGF-β1蛋白及mRNA表达最低,其余各组大鼠TGF-β1蛋白及mRNA在7 d时达到高峰,并随时间的推移逐渐下降。同一时间点,模型组大鼠TGF-β1蛋白及mRNA在肺组织中的表达明显高于其他各组(P<0.01,P<0.05),药物干预组间,泼尼松组及果王素高剂量组TGF-β1蛋白及mRNA明显低于果王素低、中剂量组(P<0.01,P<0.05),果王素高剂量组与泼尼松组间表达差异无统计学意义(P>0.05)。结论:果王素可能通过下调TGF-β1的表达抑制PF。

Objective:To explore whether Kiwi fruit essence can inhibit PF by regulating TGF-β1 by observing the effect of expression of transforming growth factor-β1(TGF-β1)protein and mRNA in the lung tissue of Bleomycin-induced pulmonary fibrosis(PF)rats that intervened by Kiwi fruit essence,and to explore the effect of its administration concentration on PF in rats.Methods:Total 128 SD rats were randomly divided into blank group,model group,prednisone group,and low,medium,high dose of Kiwi fruit essence groups(60,120,180 mg/kg).By injecting Bleomycin into the trachea to establish rats PF model.From the 2nd day after the model was established,prednisone and high dose of Kiwi fruit essence groups’rats were gavaged according to a certain ratio,blank group and model group were given the same volume of 0.9%sodium chloride solution by gavage,once a day.All rats in blank group were killed on the 28th day.In the remaining group,8 rats were killed on the 7th,14th,and 28th day,and samples were taken.The pathological changes of rat lung tissue were observed by HE and Masson staining,and the expressions of TGF-β1 protein and mRNA were detected by immunohistochemistry,Western blot and quantitative real-time PCR.Results:Kiwi fruit essence had an inhibitory effect on PF and was related to the dose.The expressions of TGF-β1 protein and mRNA in the lung tissue of the blank group was the lowest.In the remaining groups,the expressions of TGF-β1 protein and mRNA reached a peak at the 7th day,and gradually decreased over time.At the same time point,expression of TGF-β1 protein and mRNA in the lung tissues of model group was significantly higher than other groups(P<0.01,P<0.05).Among the drug intervention groups,the TGF-β1 protein and mRNA of prednisone group and high-dose Kiwi fruit group were significantly lower than low and medium-dose Kiwi fruit groups(P<0.01,P<0.05).However,there was no significant difference in the expression of Kiwi fruit high-dose group and prednisone group(P>0.05).Conclusion:Kiwi fruit may inhibit PF by down-regulating the expression of TGF-β1.