姜黄素对肺纤维化模型大鼠TGF-β_1表达的影响
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摘要
目的:探究姜黄素对肺纤维化模型大鼠TGF-β_1表达的影响。方法:将96只雄性昆明大鼠随机分为4组,空白对照组(A)、模型组(B)、阳性药物对照组(C,醋酸泼尼松片)和姜黄素干预组(D),每组24只。B、C、D均一次性气管内给予博莱霉素(5mg/kg)制作肺纤维化动物模型,空白对照组以同样方法一次性气管内注入等体积的生理盐水。28d后造模成功,然后A、B组给予等量生理盐水[0.014L/(kg·d)],C组给予醋酸泼尼松混悬液[0.56mg/(kg·d)],D组给予姜黄素羧甲基纤维素钠混悬液[200mg/(kg·d)]。观察4组大鼠肺组织HE染色、TGF-β_1表达情况。结果:(1)HE、免疫组化染色:模型组大鼠肺组织形成了稳定的肺纤维化;阳性药物对照组和姜黄素干预组肺组织纤维化情况好转明显。(2)模型组在灌注BLM后28d TGF-β_1表达水平达到高峰。模型组肺组织TGF-β_1的表达较对照组的差异有统计学意义(P<0.05)。与模型组比较,阳性药物对照组和姜黄素干预组肺组织TGF-β_1表达降低,但二者之间差异无统计学意义(P>0.05)。结论:姜黄素对大鼠肺间质纤维化具有明显的防治作用。姜黄素的作用可能是通过抑制TGF-β_1在肺组织中的表达来实现的。
Objective:To investigate the effect of curcumin on the expression of TGF-β_1 in rats with pulmonary fibrosis.Methods:96 male Kunming rats were divided into two groups, randomly divided into 4 groups, blank control group(A),Model group(B),Positive drug control group(C,prednisone acetate tablets) and curcumin intervention group(D),24 rats in each group,B,C,D were given intratracheal bleomycin(5 mg/kg) for lung production.In the animal model of fibrosis,the blank control group was injected with the same volume of normal saline in the same way.After 28 days, the model was successfully established, and then the A,B group was given the same amount of normal saline[0.014 L/(kg·d)], group C was given prednisone acetate suspension[0.56 mg/(kg·d)], group D was given curcumin sodium carboxymethyl cellulose suspension[200 mg/(kg·d)],HE staining and TGF-β_1 expression were observed in the lung tissue of 4 groups of rats.Results:HE staining: stable pulmonary fibrosis was formed in the lung tissue of the model group;pulmonary fibrosis in the positive drug control group and curcumin intervention group.The improvement of TGF-β_1 expression reached the peak in the model group at 28 days after perfusion of BLM.The expression of TGF-β_1 in the lung tissue of the model group was statistically different from that in the control group(P<0.05).Compared with the model group,the expression of TGF-β_1 in the lung tissue of the positive drug control group and curcumin intervention group was decreased, but there was no statistical difference between the two groups(P>0.05).Conclusion:Curcumin has obvious preventive and therapeutic effects on pulmonary interstitial fibrosis in rats.Curcumin may be achieved by inhibiting the expression of TGF-β_1 in lung tissue.
Objective:To investigate the effect of curcumin on the expression of TGF-β_1 in rats with pulmonary fibrosis.Methods:96 male Kunming rats were divided into two groups, randomly divided into 4 groups, blank control group(A),Model group(B),Positive drug control group(C,prednisone acetate tablets) and curcumin intervention group(D),24 rats in each group,B,C,D were given intratracheal bleomycin(5 mg/kg) for lung production.In the animal model of fibrosis,the blank control group was injected with the same volume of normal saline in the same way.After 28 days, the model was successfully established, and then the A,B group was given the same amount of normal saline[0.014 L/(kg·d)], group C was given prednisone acetate suspension[0.56 mg/(kg·d)], group D was given curcumin sodium carboxymethyl cellulose suspension[200 mg/(kg·d)],HE staining and TGF-β_1 expression were observed in the lung tissue of 4 groups of rats.Results:HE staining: stable pulmonary fibrosis was formed in the lung tissue of the model group;pulmonary fibrosis in the positive drug control group and curcumin intervention group.The improvement of TGF-β_1 expression reached the peak in the model group at 28 days after perfusion of BLM.The expression of TGF-β_1 in the lung tissue of the model group was statistically different from that in the control group(P<0.05).Compared with the model group,the expression of TGF-β_1 in the lung tissue of the positive drug control group and curcumin intervention group was decreased, but there was no statistical difference between the two groups(P>0.05).Conclusion:Curcumin has obvious preventive and therapeutic effects on pulmonary interstitial fibrosis in rats.Curcumin may be achieved by inhibiting the expression of TGF-β_1 in lung tissue.
引文
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[2] Cao H,Wang C,Chen X,et al.Inhibition of Wnt/beta-catenin signaling suppresses myofibroblast differentiation of lung resident mesenchymal stem cells and pulmonary fibrosis[J].Scientific reports,2018,8(1):13644.
[3] Kolb M,Raghu G,Wells AU,et al.Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis[J].The New England journal of medicine,2018,379(18):1722-1731.
[4] Saito A,Horie M,Micke P,et al.The Role of TGF-beta Signaling in Lung Cancer Associated with Idiopathic Pulmonary Fibrosis[J].International journal of molecular sciences,2018,19(1):147.
[5] Kim KH,Lee S,Lee H,et al.A standardized herbal extract PM014 ameliorates pulmonary fibrosis by suppressing the TGF-beta1 pathway[J].Scientific reports,2018,8:160-168.
[6] Hu Y,Li M,Zhang M,et al.Inhalation treatment of idiopathic pulmonary fibrosis with curcumin large porous microparticles[J].International journal of pharmaceutics,2018,551(1-2):212-222.
[7] Chauhan PS,Dash D,Singh R.Intranasal Curcumin Inhibits Pulmonary Fibrosis by Modulating Matrix Metalloproteinase-9 (MMP-9) in Ovalbumin-Induced Chronic Asthma[J].Inflammation,2017,40(1):248-258.
[8] Chen B,Zhang DP,Gao W.Effect of curcumin on the expression of collagen type I protein and transforming growth factor-beta1 mRNA in pulmonary fibrosis rats[J].Zhonghua lao dong wei sheng zhi ye bing za zhi,2008,26(5):257-261.
[9] 刘方兰.TGF-β1在乳腺癌微环境诱导肿瘤相关成纤维细胞形成的机制研究[D].广州:暨南大学,2016.