中华劳动卫生职业病杂志
中華勞動衛生職業病雜誌
중화노동위생직업병잡지
CHINESE JOURNAL OF INDUSTRIAL HYGIENE AND OCCUPATIONAL DISEASES
2011年
4期
255-259
,共5页
樊林花%刘田福%郭民%刘茂林%王志平%司苏晋
樊林花%劉田福%郭民%劉茂林%王誌平%司囌晉
번림화%류전복%곽민%류무림%왕지평%사소진
五味子%二氧化硅%转化生长因子β%基因表达
五味子%二氧化硅%轉化生長因子β%基因錶達
오미자%이양화규%전화생장인자β%기인표체
Schisandrn Chinenisi%Silicon dioxide%Transforming growth factor beta%Gene expression
目的 观察五味子乙素(sehisandrin B,Sch-B)对染矽尘大鼠肺组织转化生长因子β1(TGF-β1)信号通路分子mRNA表达的影响,探讨其防治矽肺纤维化的作用及机制.方法 将96只Wistar大鼠随机分为对照组、染矽尘组、Sch-B干预组,每组32只,气管暴露法一次性染尘建立大鼠矽肺模型,染矽尘组和Sch-B干预组每只大鼠气管内注入1 ml(50 mg/ml)SiO2混悬液,对照组注入1 ml灭菌生理盐水.染尘后第1天开始灌胃干预,Sch-B组给予Sch-B(80mg·kg-1/d-1),染矽尘组和对照组给予等体积的橄榄油.不同处理3、7、14和28 d后,各组处死8只大鼠,对肺组织HE染色观察病理改变;用反转录-聚合酶链式反应(RT-PCR)法测定大鼠肺组织中TGF-β1、转化生长因子βⅡ型受体(TGF-βRⅡ)和Smad4基因表达.结果 染矽尘组肺损伤明显,在3和7 d时表现为明显的肺泡炎,可见肺泡间隔水肿,大量炎性细胞浸润,在14d时,肺泡间隔明显增宽,成纤维细胞和胶原基质明显增多;在28 d时,肺泡结构破坏,肺泡壁明显增厚,肺组织以胶原沉积和肺纤维化改变为主.Sch-B组肺泡炎和肺纤维化程度均较染矽尘组明显减轻.染矽尘组3、7、14、28 d时大鼠肺内TGF-β1、TGF-βRⅡ和Smad4的mRNA表达(TGF-β1:1.03±0.31、1.33±0.39、1.08±0.26、0.82±0.16,TGF-βRⅡ:0.65±0.11、0.80±0.16、0.83±0.24、0.62±0.15,Smad4:0.87±0.15、0.68±0.11、0.78±0.19、0.30±0.08)均明显高于对照组(TGF-β1:0.59±0.22、0.55±0.25、0.56±0.20、0.55±0.12,TGR-βRⅡ:0.28±0.13、0.31 ±0.15、0.34±0.15、0.27±0.09,Smad4:0.23±0.11、0.40±0.12、0.39±0.12、0.18±0.06),差异均有统计学意义(P＜0.01或P＜0.05),其中TGF-β1在第7天时达高峰后开始下降.Sch-B干预组各时间点TGF-β1和Smad4(TGF-β1:0.68±0.28、0.88±0.25、0.75±0.11、0.61±0.14,Smad4:0.25±0.12、0.45±0.09、0.44±0.07、0.21±0.04)均低于染矽尘组,差异有统计学意义(P＜0.01或P＜0.05).与染矽尘组相比,Sch-B干预组TGF-βRⅡmRNA表达无明显改变,差异无统计学意义(P＞0.05).结论 Sch-B能减轻染矽尘大鼠肺组织的纤维化程度,其作用机制可能是通过抑制TGF-β1和Smad4的mRNA表达上调,从而干扰TGF-β1/Smad4信号通路对靶基因的激活来实现的.
目的 觀察五味子乙素(sehisandrin B,Sch-B)對染矽塵大鼠肺組織轉化生長因子β1(TGF-β1)信號通路分子mRNA錶達的影響,探討其防治矽肺纖維化的作用及機製.方法 將96隻Wistar大鼠隨機分為對照組、染矽塵組、Sch-B榦預組,每組32隻,氣管暴露法一次性染塵建立大鼠矽肺模型,染矽塵組和Sch-B榦預組每隻大鼠氣管內註入1 ml(50 mg/ml)SiO2混懸液,對照組註入1 ml滅菌生理鹽水.染塵後第1天開始灌胃榦預,Sch-B組給予Sch-B(80mg·kg-1/d-1),染矽塵組和對照組給予等體積的橄欖油.不同處理3、7、14和28 d後,各組處死8隻大鼠,對肺組織HE染色觀察病理改變;用反轉錄-聚閤酶鏈式反應(RT-PCR)法測定大鼠肺組織中TGF-β1、轉化生長因子βⅡ型受體(TGF-βRⅡ)和Smad4基因錶達.結果 染矽塵組肺損傷明顯,在3和7 d時錶現為明顯的肺泡炎,可見肺泡間隔水腫,大量炎性細胞浸潤,在14d時,肺泡間隔明顯增寬,成纖維細胞和膠原基質明顯增多;在28 d時,肺泡結構破壞,肺泡壁明顯增厚,肺組織以膠原沉積和肺纖維化改變為主.Sch-B組肺泡炎和肺纖維化程度均較染矽塵組明顯減輕.染矽塵組3、7、14、28 d時大鼠肺內TGF-β1、TGF-βRⅡ和Smad4的mRNA錶達(TGF-β1:1.03±0.31、1.33±0.39、1.08±0.26、0.82±0.16,TGF-βRⅡ:0.65±0.11、0.80±0.16、0.83±0.24、0.62±0.15,Smad4:0.87±0.15、0.68±0.11、0.78±0.19、0.30±0.08)均明顯高于對照組(TGF-β1:0.59±0.22、0.55±0.25、0.56±0.20、0.55±0.12,TGR-βRⅡ:0.28±0.13、0.31 ±0.15、0.34±0.15、0.27±0.09,Smad4:0.23±0.11、0.40±0.12、0.39±0.12、0.18±0.06),差異均有統計學意義(P＜0.01或P＜0.05),其中TGF-β1在第7天時達高峰後開始下降.Sch-B榦預組各時間點TGF-β1和Smad4(TGF-β1:0.68±0.28、0.88±0.25、0.75±0.11、0.61±0.14,Smad4:0.25±0.12、0.45±0.09、0.44±0.07、0.21±0.04)均低于染矽塵組,差異有統計學意義(P＜0.01或P＜0.05).與染矽塵組相比,Sch-B榦預組TGF-βRⅡmRNA錶達無明顯改變,差異無統計學意義(P＞0.05).結論 Sch-B能減輕染矽塵大鼠肺組織的纖維化程度,其作用機製可能是通過抑製TGF-β1和Smad4的mRNA錶達上調,從而榦擾TGF-β1/Smad4信號通路對靶基因的激活來實現的.
목적 관찰오미자을소(sehisandrin B,Sch-B)대염석진대서폐조직전화생장인자β1(TGF-β1)신호통로분자mRNA표체적영향,탐토기방치석폐섬유화적작용급궤제.방법 장96지Wistar대서수궤분위대조조、염석진조、Sch-B간예조,매조32지,기관폭로법일차성염진건립대서석폐모형,염석진조화Sch-B간예조매지대서기관내주입1 ml(50 mg/ml)SiO2혼현액,대조조주입1 ml멸균생리염수.염진후제1천개시관위간예,Sch-B조급여Sch-B(80mg·kg-1/d-1),염석진조화대조조급여등체적적감람유.불동처리3、7、14화28 d후,각조처사8지대서,대폐조직HE염색관찰병리개변;용반전록-취합매련식반응(RT-PCR)법측정대서폐조직중TGF-β1、전화생장인자βⅡ형수체(TGF-βRⅡ)화Smad4기인표체.결과 염석진조폐손상명현,재3화7 d시표현위명현적폐포염,가견폐포간격수종,대량염성세포침윤,재14d시,폐포간격명현증관,성섬유세포화효원기질명현증다;재28 d시,폐포결구파배,폐포벽명현증후,폐조직이효원침적화폐섬유화개변위주.Sch-B조폐포염화폐섬유화정도균교염석진조명현감경.염석진조3、7、14、28 d시대서폐내TGF-β1、TGF-βRⅡ화Smad4적mRNA표체(TGF-β1:1.03±0.31、1.33±0.39、1.08±0.26、0.82±0.16,TGF-βRⅡ:0.65±0.11、0.80±0.16、0.83±0.24、0.62±0.15,Smad4:0.87±0.15、0.68±0.11、0.78±0.19、0.30±0.08)균명현고우대조조(TGF-β1:0.59±0.22、0.55±0.25、0.56±0.20、0.55±0.12,TGR-βRⅡ:0.28±0.13、0.31 ±0.15、0.34±0.15、0.27±0.09,Smad4:0.23±0.11、0.40±0.12、0.39±0.12、0.18±0.06),차이균유통계학의의(P＜0.01혹P＜0.05),기중TGF-β1재제7천시체고봉후개시하강.Sch-B간예조각시간점TGF-β1화Smad4(TGF-β1:0.68±0.28、0.88±0.25、0.75±0.11、0.61±0.14,Smad4:0.25±0.12、0.45±0.09、0.44±0.07、0.21±0.04)균저우염석진조,차이유통계학의의(P＜0.01혹P＜0.05).여염석진조상비,Sch-B간예조TGF-βRⅡmRNA표체무명현개변,차이무통계학의의(P＞0.05).결론 Sch-B능감경염석진대서폐조직적섬유화정도,기작용궤제가능시통과억제TGF-β1화Smad4적mRNA표체상조,종이간우TGF-β1/Smad4신호통로대파기인적격활래실현적.
Objective To investigate the effects of schisandrin B (Sch-B) on expression of transforming growth factor-β1 (TGF-β1) and signal transduction molecule mRNA in rat lungs exposed to SiO2,and explore the intervention mechanism of Sch-B on pulmonary fibrosis induced by SiO2. Methods Ninety six Wistar rats were randomly divided into control (normal saline) group, SiO2 group and SiO2 plus Sch-B group.The rats were exposed to SiO2 by direct tracheal instillation to establish the silicotic animal models. SiO2 group and SiO2 plus Sch-B group were treated with 1ml SiO2 (50 mg/ml) for each rat From the first day after model establishment, SiO2 plus Sch-B group were orally given Sch-B (80 mg/kg) a day, control group and silica group were orally given olive oil. On the 3rd, 7th,14th and 28th days after treatment, 8 rats in each group were sacrificed and samples were collected. The histo-pathological examination of lung was performed by HE staining. The expression levels of TGF-β1 、TGFβR Ⅱ and Smad4 mRNA in the lung tissues were detected by RT-PCR. Results The results of histo-pathological examination showed that in SiO2 group, lung tissues were injured obviously; the alveolar inflammation with alveolus interval edema and inflammation cell infiltration appeared on the 3rd and 7th days; the alveolus interval became thicker, became thicker, fibroblast and collagen matiix increased markedly on 14th day; the alveolar structure was damaged, alveolar wall thickened obviously,collagen aggradation and pulmonary fibrosis displayed on 28th day. The alveolar inflammation and pulmonary fibrosis in SiO2 plus Sch-B group were significantly less than those in SiO2 group. The expressions levels of TGF-β1、TGFβR Ⅱ and Smad4 mRNA (TGF-β1: 1.03±0.31 、1.33±0.39、1.08±0.26、0.82±0.16,TGF-βR Ⅱ:0.65 ±0.11、0.80 ±0.16、0.83 ±0.24、0.62 ±0.15, Smad4: 0.87 ±0. 15、0.68 ±0.11、0.78 ±0.19、0.30 ±0.08) in SiO2group were significantly higher than those in the control group (TGF-β1:0.59±0.22、0.55 ±0.25、0.56±0.20、0.55 ±0.12,TGR-βR Ⅱ:0.28 ±0.13、0.31 ±0. 15、0.34 ±0.15、0.27 ±0.09,Smad4:0.23 ±0.11、0.40 ±0. 12、0.39 ±0.12、0.18±0.06)(P＜0.01 or P＜0.05), but the expression level of TGF-β1 mRNA was the highest on the 7th day. The expression levels of TGF-β1 and Smad4 mRNA (TGF-β1: 0.68 ±0.28、0.88 ±0.25、0.75 ±0.11、0.61 ±0. 14,Smad4:0.25 ±0.12、0.45 ±0.09、0.44 ±0.07、0.21 ±0.04) in SiO2 plus Sch-B group were significantly lower than those in SiO2 group (P＜0.01 or P＜0.05),but there were no significant differences of the TGFβR Ⅱ mRNA expression levels between SiO2 group and SiO2 plus Sch-B group. Conclusion Sch-B can reduce the pulmonary fibrosis induced by SiO2 through inhibition of the mRNA express of TGF-β1 and Smad4 in the lung tissue, modulating the TGF-β1/Smad4 signal transduction pathway and inhibiting the target gene activation.
