目的 建立未知聚合物气管滴注致SD大鼠肺组织损伤的动物模型,为探讨该未知聚合物职业暴露的损伤机制提供研究基础.方法 140只SD大鼠,随机分为5个染毒剂量组(40、30、20、10和5 mg/ml)及生理盐水对照组和动物空白对照组,每组20只.染毒组大鼠一次性气管滴注未知聚合物1.0 ml,左右肺各0.5 ml；生理盐水对照组大鼠一次性气管滴注生理盐水1.0 ml,左右肺各0.5 ml；动物空白对照组大鼠不滴注未知聚合物或生理盐水.染毒组大鼠染毒后第1、3、7、14、21和28天处死,采血进行生化指标分析,取肺组织进行病理组织学检查.结果 大鼠血生化分析结果显示,染毒后1d,40和30 mg/ml染毒组大鼠丙氨酸转氨酶和天冬氨酸转氨酶明显高于对照组.大体解剖显示,40和30 mg/ml染毒组大鼠,染毒后8h,肺粘连,色黑,有胸腔积液；染毒后7d,胸腺糜烂,肺肿大,有散在白色斑点和胸腔积液.染毒后14d,肺可见陈旧性出血点,未见胸腔积液.20 mg/ml染毒组大鼠,染毒后1d,肺肿大、粘连,呈白色状,有胸腔积液；染毒后7d,肺硬肿,有胸腔积液.10和5 rng/ml染毒组大鼠,染毒后1d,肺肿大,暗黑色,有少量胸腔积液；染毒后7d,肺间有黑点,肺硬肿,有胸腔积液；染毒后14～28 d,肺见白色硬块物质.电子显微镜观察显示,40和30 mg/ml染毒组大鼠染毒后1d,有肺泡上皮细胞肿胀和细胞膜损伤,肺泡腔内可见红细胞及中性粒细胞浸润,随着时间的延长,细胞肿胀逐渐消失,出现成纤维细胞.20mg/ml染毒组大鼠肺胞腔内中性粒细胞浸润,细胞呈游走状态,胞腔内有水肿液形成；染毒后7d,出现脱落的微绒毛,成纤维细胞核大,胞外少量胶原纤维,肺毛细血管内皮肿胀.10和5 mg/ml染毒组大鼠细胞膜损伤比较严重,胞质中线粒体明显增多,周围大量淋巴细胞浸润；染毒后7d,出现微绒毛脱落,胶原纤维形成.结论 利用SD大鼠,采用肺部气管滴注法,可成功地建立未知聚合物暴露致肺组织损伤的动物模型,动物解剖和病理学检查结果显示,大鼠肺组织损伤类型与未知聚合物暴露的临床表现一致.动物模型的建立,为进一步研究该未知聚合物职业暴露的损伤机制提供研究基础.
目的 建立未知聚閤物氣管滴註緻SD大鼠肺組織損傷的動物模型,為探討該未知聚閤物職業暴露的損傷機製提供研究基礎.方法 140隻SD大鼠,隨機分為5箇染毒劑量組(40、30、20、10和5 mg/ml)及生理鹽水對照組和動物空白對照組,每組20隻.染毒組大鼠一次性氣管滴註未知聚閤物1.0 ml,左右肺各0.5 ml；生理鹽水對照組大鼠一次性氣管滴註生理鹽水1.0 ml,左右肺各0.5 ml；動物空白對照組大鼠不滴註未知聚閤物或生理鹽水.染毒組大鼠染毒後第1、3、7、14、21和28天處死,採血進行生化指標分析,取肺組織進行病理組織學檢查.結果 大鼠血生化分析結果顯示,染毒後1d,40和30 mg/ml染毒組大鼠丙氨痠轉氨酶和天鼕氨痠轉氨酶明顯高于對照組.大體解剖顯示,40和30 mg/ml染毒組大鼠,染毒後8h,肺粘連,色黑,有胸腔積液；染毒後7d,胸腺糜爛,肺腫大,有散在白色斑點和胸腔積液.染毒後14d,肺可見陳舊性齣血點,未見胸腔積液.20 mg/ml染毒組大鼠,染毒後1d,肺腫大、粘連,呈白色狀,有胸腔積液；染毒後7d,肺硬腫,有胸腔積液.10和5 rng/ml染毒組大鼠,染毒後1d,肺腫大,暗黑色,有少量胸腔積液；染毒後7d,肺間有黑點,肺硬腫,有胸腔積液；染毒後14～28 d,肺見白色硬塊物質.電子顯微鏡觀察顯示,40和30 mg/ml染毒組大鼠染毒後1d,有肺泡上皮細胞腫脹和細胞膜損傷,肺泡腔內可見紅細胞及中性粒細胞浸潤,隨著時間的延長,細胞腫脹逐漸消失,齣現成纖維細胞.20mg/ml染毒組大鼠肺胞腔內中性粒細胞浸潤,細胞呈遊走狀態,胞腔內有水腫液形成；染毒後7d,齣現脫落的微絨毛,成纖維細胞覈大,胞外少量膠原纖維,肺毛細血管內皮腫脹.10和5 mg/ml染毒組大鼠細胞膜損傷比較嚴重,胞質中線粒體明顯增多,週圍大量淋巴細胞浸潤；染毒後7d,齣現微絨毛脫落,膠原纖維形成.結論 利用SD大鼠,採用肺部氣管滴註法,可成功地建立未知聚閤物暴露緻肺組織損傷的動物模型,動物解剖和病理學檢查結果顯示,大鼠肺組織損傷類型與未知聚閤物暴露的臨床錶現一緻.動物模型的建立,為進一步研究該未知聚閤物職業暴露的損傷機製提供研究基礎.
목적 건립미지취합물기관적주치SD대서폐조직손상적동물모형,위탐토해미지취합물직업폭로적손상궤제제공연구기출.방법 140지SD대서,수궤분위5개염독제량조(40、30、20、10화5 mg/ml)급생리염수대조조화동물공백대조조,매조20지.염독조대서일차성기관적주미지취합물1.0 ml,좌우폐각0.5 ml；생리염수대조조대서일차성기관적주생리염수1.0 ml,좌우폐각0.5 ml；동물공백대조조대서불적주미지취합물혹생리염수.염독조대서염독후제1、3、7、14、21화28천처사,채혈진행생화지표분석,취폐조직진행병리조직학검사.결과 대서혈생화분석결과현시,염독후1d,40화30 mg/ml염독조대서병안산전안매화천동안산전안매명현고우대조조.대체해부현시,40화30 mg/ml염독조대서,염독후8h,폐점련,색흑,유흉강적액；염독후7d,흉선미란,폐종대,유산재백색반점화흉강적액.염독후14d,폐가견진구성출혈점,미견흉강적액.20 mg/ml염독조대서,염독후1d,폐종대、점련,정백색상,유흉강적액；염독후7d,폐경종,유흉강적액.10화5 rng/ml염독조대서,염독후1d,폐종대,암흑색,유소량흉강적액；염독후7d,폐간유흑점,폐경종,유흉강적액；염독후14～28 d,폐견백색경괴물질.전자현미경관찰현시,40화30 mg/ml염독조대서염독후1d,유폐포상피세포종창화세포막손상,폐포강내가견홍세포급중성립세포침윤,수착시간적연장,세포종창축점소실,출현성섬유세포.20mg/ml염독조대서폐포강내중성립세포침윤,세포정유주상태,포강내유수종액형성；염독후7d,출현탈락적미융모,성섬유세포핵대,포외소량효원섬유,폐모세혈관내피종창.10화5 mg/ml염독조대서세포막손상비교엄중,포질중선립체명현증다,주위대량림파세포침윤；염독후7d,출현미융모탈락,효원섬유형성.결론 이용SD대서,채용폐부기관적주법,가성공지건립미지취합물폭로치폐조직손상적동물모형,동물해부화병이학검사결과현시,대서폐조직손상류형여미지취합물폭로적림상표현일치.동물모형적건립,위진일보연구해미지취합물직업폭로적손상궤제제공연구기출.
Objective To establish an animal model of lung injury in SD rats using intratracheal instillation of unknown polymer and to provide the base for exploring the molecular mechanism of lung tissue injury induced by occupational exposure.Methods One hundred forty SD rats were randomly divided into seven groups,including the control grouplwhich was exposed to normal solution,the control group2 which was not exposed to any one and five treatment groups which were exposed to 1 nl unknown polymer(0.5 ml for each lung)at the doses of 40,30,20,10 and 5 mg/ml,respectively by intratracheal instillation.The rats were sacrificed on the 1st,3rd,7th,10th,14th,21th and 28th day after exposure,then the lung tissues were examined pathologically and the blood bio-chemical analysis was conducted.Results The results of blood biochemical analysis indicated that ALT and AST levels in rats exposed to 30 and 40 mg/ml unknown polymer were significantly higher than those in control groups.Intratracheal instillation of unknown polymer can causes PLF in experimental animals on the 14th days after exposure.The results of pathological examination exhibited that the lung tissue injury in rats exposed to unknown polymer for 14 days or more was found and the dose-effect relationship was observed.Conclusion An animal model of lung injury in SD rats induced by unknown polymer with intratracheal instillation was established successfully.The results of pathological examination showed that the types of rat lung injury were similar to the clinical lung injury after exposure to unknown polymer,which provided a base for studying the mechanism of lung injury caused by occupational exposure to unknown polymer.
