CAJ | 학술논문

目的：观察阿托伐他汀对百草枯中毒所致肺纤维化疗效,并探讨其可能的作用机制。方法取健康成年 SD 大鼠120只,随机分为生理盐水组和百草枯组,每组10只,百草枯+阿托伐他汀10、20、40 mg 组(实验1、2、3组),百草枯+阿托伐他汀40 mg +吡格列酮组(PLZ 组)和百枯草+阿托伐他汀40 mg + GW9662组(GW9662组),每组20只。百草枯肺间质纤维化模型以百草枯溶液3.5 mg/ kg 的剂量腹腔注射制备,生理盐水组则以等体积的生理盐水腹腔注射,其余各药物干预组均在建立百草枯模型的基础上给予相应的药物,连续给药14 d 后处死大鼠,比较各组大鼠肺泡灌洗液中炎性细胞数目、肺组织中羟脯氨酸、血清中转化生长因子(TGF)-β1的含量。结果肺泡灌洗液中炎性细胞数目、肺组织中羟脯氨酸、血清中 TGF-β1的含量百草枯组均高于生理盐水组,实验2、3组均低于百草枯组(P <0．05,P <0．01)。 GW9662组肺泡灌洗液中炎性细胞数目和肺组织中羟脯氨酸低于实验3组,PLZ 组高于实验3组(P <0．05,P <0．01)。 GW9662组和 PLZ 组血清中 TGF-β1的含量均高于实验3组,但 PLZ 组升高更明显(P <0．05,P <0．01)。结论阿托伐他汀可缓解百草枯中毒所致的肺纤维化,且呈剂量依赖的方式,其作用机制可能是通过 PPARγ途径而实现。
목적：관찰아탁벌타정대백초고중독소치폐섬유화료효,병탐토기가능적작용궤제。방법취건강성년 SD 대서120지,수궤분위생리염수조화백초고조,매조10지,백초고+아탁벌타정10、20、40 mg 조(실험1、2、3조),백초고+아탁벌타정40 mg +필격렬동조(PLZ 조)화백고초+아탁벌타정40 mg + GW9662조(GW9662조),매조20지。백초고폐간질섬유화모형이백초고용액3.5 mg/ kg 적제량복강주사제비,생리염수조칙이등체적적생리염수복강주사,기여각약물간예조균재건립백초고모형적기출상급여상응적약물,련속급약14 d 후처사대서,비교각조대서폐포관세액중염성세포수목、폐조직중간포안산、혈청중전화생장인자(TGF)-β1적함량。결과폐포관세액중염성세포수목、폐조직중간포안산、혈청중 TGF-β1적함량백초고조균고우생리염수조,실험2、3조균저우백초고조(P <0．05,P <0．01)。 GW9662조폐포관세액중염성세포수목화폐조직중간포안산저우실험3조,PLZ 조고우실험3조(P <0．05,P <0．01)。 GW9662조화 PLZ 조혈청중 TGF-β1적함량균고우실험3조,단 PLZ 조승고경명현(P <0．05,P <0．01)。결론아탁벌타정가완해백초고중독소치적폐섬유화,차정제량의뢰적방식,기작용궤제가능시통과 PPARγ도경이실현。
Objective To observe the curative effects of Atorvastatin on Paraquat (PQ)-induced pulmonary fi-brosis and to explore the possible mechanisms. Methods A total of 120 healthy adult SD rats were randomly divided into normal saline group (n = 10), PQ poisoned group (n = 10), PQ and Atorvastatin at the dose of 10, 20 or 40 mg groups (experiment group 1, 2 and 3, n = 20 for each group), PQ, Atorvastatin at the dose of 40mg and Pioglitazone group (PLZ group, n = 20) and PQ, Atorvastatin at the dose of 40mg and GW9662 group (GW9662 group, n = 20). The PQ-induced pulmonary fibrosis models were established with 3. 5 mg/ kg PQ solutions by intraperitoneal injection, and the models of normal saline group were established with the same volume of normal saline by intraperitoneal injection. All the drug intervention groups were given corresponding drugs after the establishment of PQ models, and all the SD rats were sacrificed at the 14th d of continous administration, and then the amount of inflammatory cells in alveolar lavage fluid, the content of hydroxyproline in lung tissues and the content of serum TGF-β1 ( transforming growth factor-β1 ) among all groups were compared. Results The values of amount of inflammatory cells in alveolar lavage fluid, the content of hydroxyproline in lung tissues and the content of serum TGF-β1 in PQ poisoned group were significantly higher than those in normal saline group, and the values in experiment group 2 and 3 were less significant than those in PQ group (P <0. 05, P < 0. 01). The values of amount of inflammatory cells in alveolar lavage fluid and the content of hydroxyproline in lung tissues in GW9662 group were less significant than those in experiment group 3, while the values in PLZ group were significantly higher than those in experiment group 3 (P < 0. 05, P < 0. 01). The values of serum TGF-β1 content in PLZ group and GW9662 were significantly higher than that in experiment group 3, but the increased value was more obvious in PLZ group (P < 0. 05, P < 0. 01). Conclusion Atorvastatin can alleviate the PQ-induced pulmonary fibrosis with a dose-dependent manner, and the mechanisms may be achieved through PPARγ.