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
2期
87-93
,共7页
李军伟%沈秀微%孙未%肖敏%仝淑花%虞希冲%卢中秋%胡国新
李軍偉%瀋秀微%孫未%肖敏%仝淑花%虞希遲%盧中鞦%鬍國新
리군위%침수미%손미%초민%동숙화%우희충%로중추%호국신
百草枯%肺纤维化%吡非尼酮%羟脯氨酸%转化生长因子β
百草枯%肺纖維化%吡非尼酮%羥脯氨痠%轉化生長因子β
백초고%폐섬유화%필비니동%간포안산%전화생장인자β
Paraquat%Pulmonary fibrosis%Pirfenidone%Hydroxyproline%Transforming growth factor β
目的 探讨吡非尼酮(PF)对百草枯(PQ)中毒小鼠肺纤维化的治疗作用,为临床治疗提供理论依据.方法 雄性ICR小鼠90只,随机分为正常对照组、PQ组、地塞米松组、25、50和100 mg/kgPF组,每组15只.正常对照组小鼠一次性空腹灌胃给予生理盐水,2 h后给予质量分数为1%羧甲基纤维素(CMC)灌胃,再每天定时空腹灌胃同等量CMC;PQ组、地塞米松组及各PF剂量组小鼠给予PQ100mg/kg一次性灌胃染毒,灌胃后2 h,再每天定时PQ组给予0.02ml/10 gCMC灌肠,PF组给予PF(25、50、100 mg/kg)和地塞米松(0.02 ml/10 g)灌胃,每天1次,共49 d.计算肺系数,HE染色,光学显微镜下观察肺组织病理改变;测定肺组织羟脯氨酸(HYP)含量,转化生长因子(TGF-β1)的mRNA表达水平、蛋白表达水平,支气管肺泡灌洗液(BALF)中的TGF-β1蛋白含量.结果 PQ组3 d生存率为53.33%,25、50、100 mg/kg PF组3 d生存率分别为46.67%、73.33%、86.67%,地塞米松组3 d生存率为80%,地塞米松组、50、100 mg/kg PF组3 d生存率明显高于PQ组和25 mg/kg PF组,差异有统计学意义(P＜0.05).25、50及100mg/kg PF组小鼠肺系数均明显低于PQ组,差异有统计学意义(P＜0.05).地塞米松组肺组织中HYP含量为(50.95±11.65)mg/g,25、50、100mg/kg PF组HYP含量分别为(44.52±9.48)、(43.27±6.01)、(40.82±5.90)mg/g,较PQ组[(74.27±3.68)mg/g]明显下降,差异均有统计学意义(P＜0.01).地塞米松组BALF中TGF-β1蛋白含量为(22.03±7.27)mg/ml,25、50、100 mg/kg PF组TGF-β1蛋白含量分别为(55.33±17.50)、(27.75±5.84)、(21.31±6.82)mg/ml,与PQ组[(52.52±15.51)mg/ml]相比,明显降低,差异有统计学意义(P＜0.01);100 mg/kg PF组肺组织TGF-β1mRNA表达水平与PQ组相比,明显下降,差异有统计学意义(P＜0.01)与PQ组比较,地塞米松组,50、100mg/kgPF组肺组织中TGF-β1蛋白表达下降,差异有统计学意义(P＜0.01).结论 PF可以减少百草枯中毒小鼠肺组织胶原沉积,减轻肺部纤维化程度.
目的 探討吡非尼酮(PF)對百草枯(PQ)中毒小鼠肺纖維化的治療作用,為臨床治療提供理論依據.方法 雄性ICR小鼠90隻,隨機分為正常對照組、PQ組、地塞米鬆組、25、50和100 mg/kgPF組,每組15隻.正常對照組小鼠一次性空腹灌胃給予生理鹽水,2 h後給予質量分數為1%羧甲基纖維素(CMC)灌胃,再每天定時空腹灌胃同等量CMC;PQ組、地塞米鬆組及各PF劑量組小鼠給予PQ100mg/kg一次性灌胃染毒,灌胃後2 h,再每天定時PQ組給予0.02ml/10 gCMC灌腸,PF組給予PF(25、50、100 mg/kg)和地塞米鬆(0.02 ml/10 g)灌胃,每天1次,共49 d.計算肺繫數,HE染色,光學顯微鏡下觀察肺組織病理改變;測定肺組織羥脯氨痠(HYP)含量,轉化生長因子(TGF-β1)的mRNA錶達水平、蛋白錶達水平,支氣管肺泡灌洗液(BALF)中的TGF-β1蛋白含量.結果 PQ組3 d生存率為53.33%,25、50、100 mg/kg PF組3 d生存率分彆為46.67%、73.33%、86.67%,地塞米鬆組3 d生存率為80%,地塞米鬆組、50、100 mg/kg PF組3 d生存率明顯高于PQ組和25 mg/kg PF組,差異有統計學意義(P＜0.05).25、50及100mg/kg PF組小鼠肺繫數均明顯低于PQ組,差異有統計學意義(P＜0.05).地塞米鬆組肺組織中HYP含量為(50.95±11.65)mg/g,25、50、100mg/kg PF組HYP含量分彆為(44.52±9.48)、(43.27±6.01)、(40.82±5.90)mg/g,較PQ組[(74.27±3.68)mg/g]明顯下降,差異均有統計學意義(P＜0.01).地塞米鬆組BALF中TGF-β1蛋白含量為(22.03±7.27)mg/ml,25、50、100 mg/kg PF組TGF-β1蛋白含量分彆為(55.33±17.50)、(27.75±5.84)、(21.31±6.82)mg/ml,與PQ組[(52.52±15.51)mg/ml]相比,明顯降低,差異有統計學意義(P＜0.01);100 mg/kg PF組肺組織TGF-β1mRNA錶達水平與PQ組相比,明顯下降,差異有統計學意義(P＜0.01)與PQ組比較,地塞米鬆組,50、100mg/kgPF組肺組織中TGF-β1蛋白錶達下降,差異有統計學意義(P＜0.01).結論 PF可以減少百草枯中毒小鼠肺組織膠原沉積,減輕肺部纖維化程度.
목적 탐토필비니동(PF)대백초고(PQ)중독소서폐섬유화적치료작용,위림상치료제공이론의거.방법 웅성ICR소서90지,수궤분위정상대조조、PQ조、지새미송조、25、50화100 mg/kgPF조,매조15지.정상대조조소서일차성공복관위급여생리염수,2 h후급여질량분수위1%최갑기섬유소(CMC)관위,재매천정시공복관위동등량CMC;PQ조、지새미송조급각PF제량조소서급여PQ100mg/kg일차성관위염독,관위후2 h,재매천정시PQ조급여0.02ml/10 gCMC관장,PF조급여PF(25、50、100 mg/kg)화지새미송(0.02 ml/10 g)관위,매천1차,공49 d.계산폐계수,HE염색,광학현미경하관찰폐조직병리개변;측정폐조직간포안산(HYP)함량,전화생장인자(TGF-β1)적mRNA표체수평、단백표체수평,지기관폐포관세액(BALF)중적TGF-β1단백함량.결과 PQ조3 d생존솔위53.33%,25、50、100 mg/kg PF조3 d생존솔분별위46.67%、73.33%、86.67%,지새미송조3 d생존솔위80%,지새미송조、50、100 mg/kg PF조3 d생존솔명현고우PQ조화25 mg/kg PF조,차이유통계학의의(P＜0.05).25、50급100mg/kg PF조소서폐계수균명현저우PQ조,차이유통계학의의(P＜0.05).지새미송조폐조직중HYP함량위(50.95±11.65)mg/g,25、50、100mg/kg PF조HYP함량분별위(44.52±9.48)、(43.27±6.01)、(40.82±5.90)mg/g,교PQ조[(74.27±3.68)mg/g]명현하강,차이균유통계학의의(P＜0.01).지새미송조BALF중TGF-β1단백함량위(22.03±7.27)mg/ml,25、50、100 mg/kg PF조TGF-β1단백함량분별위(55.33±17.50)、(27.75±5.84)、(21.31±6.82)mg/ml,여PQ조[(52.52±15.51)mg/ml]상비,명현강저,차이유통계학의의(P＜0.01);100 mg/kg PF조폐조직TGF-β1mRNA표체수평여PQ조상비,명현하강,차이유통계학의의(P＜0.01)여PQ조비교,지새미송조,50、100mg/kgPF조폐조직중TGF-β1단백표체하강,차이유통계학의의(P＜0.01).결론 PF가이감소백초고중독소서폐조직효원침적,감경폐부섬유화정도.
Objective To study the curative effects of pirfenidone (PF)on pulmonary fibrosis induced by paraquat (PQ) in mice and to provide the theoretical basis for clinical treatment. Methods Ninety adult healthy male ICR mice were randomly divided into six groups: control group, PQ group , 2 mg/kg Dexamethasone group, 25 mg/kg PF group, 50 mg/kg PF group and 100 mg/kg PF group, there were 15 mice in each group. The corresponding volume of normal saline was given to the each mouse in control group according to the weight, after 2 h 0.1% CMC was given to the each mouse of control group one time by intragastric administration, then the CMC was administrated at regular time until sacrifice. All mice for other 5 groups were exposed to 100 mg/kg PQ by intragastric administration. At 2 h after exposure to PQ, 0.02 ml/10 g dexamethasone and 25、50、100 mg/kg PF were given to mice for dexamethasone group and for 3 PF groups by intragastric administration each day for 49 days, respectively. The lung coefficient was calculated and pathological changes of lung tissue were observed by HE staining for each mouse. The hydroxyproline (HYP)level in lung tissue was measured for each mouse. The mRNA level of and the protein level of TGF-β1 in lungtissue for each mouse were determined, and the protein level of TGF-β1 in the bronchus-alveolus lavage fluid (BALF) of each mouse was detected. Results The survival rates on the 3rd day in PQ group, 3 PF groups and dexamethasone group were 53.33%, 46.67%, 73.33%, 86.67% and 80%, respectively. The survival rates on the 3rd day in dexamethasone group, 50 mg/kg and 100 mg/kg PF groups were significantly higher than those of PQ group and 25 mg/kg PF group (P＜0.05). The lung coefficients of 3 PF groups were significantly lower than that of the PQ group (P＜0.05). The lung tissue HYP levels of dexamethasone group and 3 PF groups were 50.95±11.65, 44.52±9.48, 43.27±6.01 and 40.82±5.90 mg/g respectively, which were significantly lower than that (74.27±3.68) of PQ group(P＜0.01 ). The TGF-β1 protein levels of BALF in dexamethasone group, 50 and 100 mg/kg PF groups were 22.03±7.27, 27.75±5.84 and 21.31 ±6.82 ng/ml respectively, which were significantly lower than that(52.52±15.51 ) ng/mlof PQ group(P＜0.01 ). The expression level of TGF-β1 mRNA in 100 mg/kg PF group decreased significantly, as compared with PQ group (P＜0.01). Conclusion PF could reduce the collagen deposition and pulmonary fibrosis induced by PQ in mice lungs.
