五味子提取物对小鼠银屑病样皮损的抑制作用及机制研究

目的 探讨五味子提取物对小鼠银屑病样皮损的抑制作用及机制。方法 使用咪喹莫特乳剂建立小鼠银屑病背部皮损模型,将小鼠分为对照组、模型组、他克莫司5 mg/kg组以及五味子提取物0.05、0.25 mg/kg组,并于造模后在小鼠背部皮肤涂抹相应药物。取小鼠背部皮肤组织,分析皮损症状,对其进行苏木精–伊红（HE）染色,并观察测定表皮厚度。免疫组织化学测定淋巴细胞表面分子（CD-8）、环氧化酶-2(COX-2)、细胞外调节蛋白激酶（ERK）、磷酸化细胞外调节蛋白激酶（p-ERK）的表达情况。建立3D皮肤模型,使用双氧水造模后,噻唑蓝（MTT）检测五味子提取物抗氧化修复活性、酶联免疫吸附法检测皮肤模型组织中超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的酶活力和炎症因子白细胞介素-6(IL-6)的含量。结果 五味子提取物可以缓解由咪喹莫特乳剂诱导的小鼠银屑病皮肤损伤、红斑、炎症,改善其皮损处组织细胞情况,降低银屑病模型小鼠表皮厚度（P<0.05）;五味子提取物可以下调银屑病模型小鼠皮肤组织中COX-2、ERK、pERK、CD-8的表达（P<0.05、0.01）;3D皮肤模型检测结果显...     

血红素氧合酶-1对哮喘小鼠模型IL-25和MUC5AC表达的影响

摘要：目的　探讨血红素氧合酶-1（HO-1）对哮喘小鼠气道炎症的调节作用及其机制。方法　将28只健康雌性Balb/c小鼠根据随机数字表法分为4组：对照组、哮喘组、血晶素组、福多司坦组,每组7只。哮喘组、血晶素组和福多司坦组小鼠于第1天和第14天腹腔注射20 μg卵清蛋白（OVA）+500 μg Al（OH）3+0.2 mL PBS致敏,于第25~28天每天雾化吸入1次OVA激发气道高反应制备小鼠哮喘模型,对照组以等量生理盐水替代,血晶素组致敏前1、2 d,致敏后12、13、23、24、27 d腹腔注射血晶素75 μmol/kg,福多司坦组分别于致敏前25、26、27 d灌胃给药福多司坦（200 mg/kg）,末次激发后24 h内处死小鼠并收集血液、肺组织。HE染色观察肺组织形态学改变,免疫组化检测肺组织黏蛋白5AC（MUC5AC）的表达,酶联免疫吸附测定（ELISA）法检测肺组织中MUC5AC和血清中白细胞介素（IL）-25的水平,并对MUC5AC和IL-25进行相关性分析。结果　哮喘组肺组织可见大量炎症细胞浸润、气管黏膜增厚、黏膜下水肿,血晶素组和福多司坦组可见少量炎症细胞浸润及渗出,病理改变较哮喘组轻。与对照组相比,哮喘组、血晶素组、福多司坦组MUC5AC和IL-25的表达水平明显升高（P＜0.05）;与哮喘组相比,血晶素组和福多司坦组MUC5AC和IL-25降低（P＜0.05）,且血晶素组较福多司坦组降低更明显（P＜0.05）。MUC5AC与IL-25的表达水平呈正相关（r=0.932,P＜0.01）。结论　HO-1可下调哮喘小鼠MUC5AC和IL-25的表达,减轻气道炎症和黏液高分泌。     

布地奈德吸入给药对慢性支气管哮喘小鼠HpARIh/STAT信号通路的影响

目的 探讨布地奈德吸入给药对慢性支气管哮喘模型小鼠多形螺旋线虫预警素释放抑制剂/转录因子（HpARIh/STAT）信号通路的影响。方法 30只小鼠随机分成3组,对照组、模型组和布地奈德组,每组10只。模型组小鼠于第1天和第14天用卵白蛋白（OVA）致敏,第24天开始雾化吸入1% OVA并持续刺激至第28天,建立哮喘气道重塑模型;布地奈德组小鼠在吸入OVA 2 h前吸入布地奈德30 min;对照组使用生理盐水代替OVA。第28天最后一次雾化结束后24 h处死小鼠,采用病理图像分析系统测量小鼠的气道形态学参数,分别取各组小鼠外周血和肺组织,用ELISA试剂盒检测外周血上清液肿瘤坏死因子（TNF-α）、白细胞介素13（IL-13）和转化生长因子-β（TGF-β）水平,HE染色观察肺组织病理学变化,Western blotting检测肺组织蛋白HpARIh、IL-13、STAT3和STAT6的表达。结果 病理组织学结果显示布地奈德组小鼠支气管壁的炎性细胞浸润明显减少,支气管壁结构改变明显减轻。HE染色结果显示布地奈德干预后有效地减少了炎性因子对肺组织的浸润。ELISA结果显示布地奈德组与模型组相比,外周血上清中TNF-α、TGF-β和IL-13等炎症因子水平明显降低（P<0.05）,但仍高于对照组。Western blotting结果表明布地奈德通过增加HpARIh蛋白表达来激活STAT3,同时抑制STAT6,从而抑制哮喘诱发因子IL-13的表达水平。结论 早期雾化吸入布地奈德可以有效抑制TNF-α、TGF-β和IL-13等炎症因子的表达,同时通过激活HpARIh/STAT信号通路抑制IL-13的表达,明显减轻哮喘小鼠的气道重塑。     

天贝止喘汤对支气管哮喘小鼠Th1/Th2影响的研究

目的观察天贝止喘汤对支气管哮喘小鼠肺组织、血清Ig E、支气管肺泡灌洗液IL-4、IL-10、IL-12和TNF-α影响,研究天贝止喘汤保护哮喘小鼠可能的机制。方法 70只健康SPF级雌性BALB/c小鼠适应性饲养后,分为7组(空白对照组、哮喘模型组、天贝止喘汤低剂量组、天贝止喘汤中剂量组、天贝止喘汤高剂量组、小青龙组、地塞米松组),10只/组。卵清白蛋白建立小鼠支气管哮喘气道炎症模型,取材后观察肺组织变化、测定血清Ig E、支气管肺泡灌洗液IL-4、IL-10、IL-12和TNF-α水平变化。结果空白组肺组织无明显炎症细胞浸润、肺组织及气道壁形态结构完整;模型组肺组织有大量炎症细胞浸润、肺组织及气道壁增厚明显,结构受损,其余各药物治疗组较模型组均有不同程度改善。与空白组相比,模型组和各药物治疗组血清Ig E水平、支气管肺泡灌洗液IL-4、TNF-α水平显著升高(P<0.05),IL-10、IL-12水平显著降低(P<0.05);与模型组相比,各药物治疗组血清Ig E水平、支气管肺泡灌洗液IL-4、TNF-α水平显著降低(P<0.05),IL-10、IL-12水平显著升高(P<0.05)。结论天贝止喘汤可能通过调节Th1/Th2平衡,调节炎性细胞因子水平保护哮喘小鼠,高剂量效果更明显。     

植物多糖和吡格列酮对小鼠肺腺癌干预效果的研究

目的观察植物多糖和吡格列酮对小鼠肺腺癌的干预效果,探讨炎症和肺腺癌之间的关系,为临床肺腺癌的治疗提供理论基础。方法100 只小鼠分为对照组、模型组、植物多糖组、吡格列酮组、植物多糖和吡格列酮联合干预组(联合组),每组20 只;植物多糖组给予植物多糖溶液500 mg/kg,吡格列酮组给予吡格列酮溶液15 mg/kg,联合组给予500 mg/kg 植物多糖+15 mg/kg 吡格列酮;对照组和模型组给予等量生理盐水(10 mL/kg),均1 次/d,5 d/周;共 20 周。观察各组不同时间小鼠肺腺癌成瘤情况,分别于第12 周和20 周,处死小鼠后检测各组核因子（NF）-κB、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-6 含量。结果对照组小鼠体质量平稳上升,其余组小鼠在乌拉坦注射期体质量持续下降,然后持续上升;第20 周,对照组小鼠肺表面未见结节,其余组均见明显的肺结节,且小鼠肺的脏器指数明显高于对照组;在第12 周和20 周时,模型、吡格列酮、植物多糖和联合组小鼠体内的NF-κB、TNF-α、 IL-1β和IL-6 含量均高于对照组,吡格列酮、植物多糖和联合组小鼠体内的NF-κB、TNF-α、IL-1β和IL-6 含量均低于模型组。结论持续的炎症反应是肺腺癌发生发展的危险因素之一,植物多糖和吡格列酮均能降低肺腺癌小鼠体内的炎症水平,提示可将其用于临床肺腺癌的药物辅助治疗。     

芹菜素对百草枯致小鼠肺纤维化保护作用及机制研究

目的 研究芹菜素对百草枯致小鼠肺纤维化的保护作用及机制。方法 将小鼠随机分为对照组、模型组、地塞米松组（1 mg/kg）和芹菜素低、高剂量（10、20 mg/kg）组,除对照组外,其他各组ip百草枯（50 mg/kg）建立小鼠肺纤维化模型,第8天开始ig给药,连续给药21 d。观察小鼠体质量变化;测量小鼠肺系数;采用HE染色观察肺组织形态学变化;免疫组化法观察小鼠肺组织中Ⅰ、Ⅲ型胶原表达变化;ELISA法检测各组小鼠肺组织中Ⅰ、Ⅲ型胶原和炎症因子肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-1β含量;Western blotting法测定肺组织Caveolin-1蛋白表达水平。结果 造模第28天时,与模型组比较,芹菜素低、高剂量组小鼠体质量显著增加（P<0.05）;地塞米松组和芹菜素低、高剂量组肺系数显著降低（P<0.05）;芹菜素低、高剂量组肺组织内炎性细胞浸润较少、肺泡壁断裂及肺泡腔融合较少,肺纤维化程度较轻;芹菜素低、高剂量组和地塞米松组小鼠的肺组织中Ⅰ、Ⅲ型胶原和IL-6、IL-1β、TNF-α含量显著下降（P<0.01）,Caveolin-1蛋白表达显著下降（P<0.01）。结论 芹菜素对百草枯诱导小鼠肺纤维化具有保护作用,其机制可能与Ⅰ、Ⅲ型胶原含量及炎症因子水平下调、Caveolin-1蛋白表达水平下调相关。     

注射用丹参多酚酸对角叉菜胶诱导的慢性尾部血栓小鼠的抗炎性血栓作用研究

目的 通过ip角叉菜胶（Ca）溶液建立小鼠慢性尾部血栓模型,尾iv给予注射用丹参多酚酸（SAFI）,探究其抗炎症血栓作用。方法 将168只KM雄性小鼠随机分为6组：对照组,模型组,SAFI低、中、高剂量（8.365、16.730、33.460 mg·kg^-1）组,造模同时给药组（即造模的同时予以SAFI给药,其余组于造模后给药,16.730 mg·kg^-1）。连续4 d ip 0.06% Ca（10 mL·kg^-1）制备血栓模型,4 d后,对照组和模型组尾iv 0.9%氯化钠注射液,其余各组分别尾iv相应剂量的SAFI,每天1次,给药7 d。给药开始后每天记录各组小鼠的出栓情况;给药结束后各组小鼠摘眼球取血,试剂盒法检测血清中6-酮-前列腺素F1α（6-keto-PGF1α）、血栓素B2（TXB2）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）水平,取尾部组织进行病理切片,HE染色观察组织损伤。结果 模型组小鼠出栓率随时间延长增加,在给药第5天出栓率达到100%;SAFI各剂量组小鼠出栓率均低于同一天的模型组,且低、中、高剂量组小鼠出栓率结果存在一定的剂量相关性;造模同时给药组出栓率均低于同一天的模型组,且相比于同一剂量（中剂量组）出栓率更低。与模型组比较,SAFI中、高剂量组和造模同时给药组血清中TXB2水平显著降低（P＜0.05、0.01、0.001）,6-keto-PGF1α水平显著升高（P＜0.01、0.001）; SAFI低剂量组小鼠血清IL-6水平显著降低（P＜0.05）,中、高剂量组和造模同时给药组小鼠血清TNF-α、IL-1β、IL-6水平显著降低（P＜0.05、0.01、0.001）; SAFI高剂量组、造模同时给药组血栓情况均明显改善。结论 ip 0.06% Ca制备的炎症血栓小鼠模型稳定、可靠,SAFI能改善炎症血栓小鼠血清中6-keto-PGF1α、TXB2、IL-6、IL-1β、TNF-α水平,有效缓解炎性因子导致的血栓症状。     

基于cGAS-STING通路探讨知母皂苷元对脂多糖诱导的小鼠急性肺损伤保护作用

目的 研究知母皂苷元对脂多糖（LPS）诱导的小鼠急性肺损伤的保护作用。方法 将昆明小鼠随机分为对照组、模型组、地塞米松（0.5 mg/kg）组、知母皂苷元（50、100、200 mg/kg）组。知母皂苷元50、100、200 mg/kg组小鼠ig相应剂量知母皂苷元溶液,地塞米松组小鼠ip地塞米松磷酸钠注射液,对照组和模型组小鼠ig等体积生理盐水,1次/d,连续7 d。末次给药1 h后,其余各组小鼠除对照组外均ip 10 mg/kg LPS溶液复制小鼠急性肺损伤模型。6 h后取各组小鼠左肺组织,计算肺湿/干质量比（W/D）;采用苏木精-伊红（HE）染色法观察肺组织病理形态学变化;采用酶联免疫吸附测定法（ELISA）检测血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平;采用Western blotting法检测肺组织中鸟苷酸-腺苷酸合成酶（cGAS）、干扰素基因刺激因子（STING）的蛋白表达。结果 与模型组相比,知母皂苷元组小鼠左肺W/D值、血清中IL-6和TNF-α水平、肺组织中cGAS和STING的蛋白表达均显著降低（P<0.05）,肺组织病理学损伤均有所改善。结论 知母皂苷元可能通过抑制cGAS-STING通路,减少炎症因子TNF-α、IL-6的分泌,从而保护LPS诱导的急性肺损伤。     

全反式维甲酸抑制IL-23/IL-17通路促进小鼠移植皮肤存活的研究

【摘要】目的探讨全反式维甲酸(ATRA)灌胃对小鼠同种异基因皮肤移植存活时间的影响及白细胞介素(IL)-23、IL-17通路在其中的作用。方法以DBA/2小鼠为供者,Babl/c小鼠为受者建立皮肤移植模型。随机将受者分为对照组、小剂量组和大剂量组,分别在术前1d至术后14d或判定皮肤死亡之日每天给3组小鼠分别灌胃注射玉米油、10mg/kg和30mg/kg ATRA玉米油溶液。术后观察各组皮肤移植物存活时间,皮肤组织切片检测病理改变,酶联免疫吸附试验检测血清IL-23和IL-17水平,实时荧光定量PCR检测移植皮肤中IL-23、转录因子孤核受体（ROR）γt和IL-17mRNA表达。结果与对照组比较,小剂量组和大剂量组皮肤移植存活时间延长（P<0.05）,炎症细胞浸润及组织破坏程度轻,血清IL-23水平降低（P<0.05）,而两治疗组间差异无统计学意义。对照组、小剂量组及大剂量组血清IL-17水平依次降低（P<0.05）。小剂量组和大剂量组皮肤移植物中IL-23、RORγt和IL-17mRNA表达水平均较对照组低（P<0.05）,而两治疗组间差异无统计学意义。结论ATRA灌胃可显著延长小鼠移植皮肤存活时间,其机制可能与抑制IL-23、RORγt、IL-17mRNA表达和蛋白分泌有关。     

三叶青藤正丁醇部位对DBA/1小鼠胶原性关节炎的作用及机制

目的：观察三叶青藤正丁醇部位（nbuIR）对胶原性关节炎小鼠关节病变及血清炎症因子的抑制作用。方法：用DBA/1小鼠建立胶原性关节炎（CIA）动物模型,将造模成功小鼠随机分为模型对照组、甲氨蝶呤组、nbuIR低、中、高剂量组,另设正常对照组。灌胃给药,给药期间每周进行一次关节炎指数评分。干预结束后,ELISA法检测各组小鼠血清IL-23和IL-17水平,H-E染色观察各组小鼠踝关节组织病理学改变。结果：与模型对照组比较,nbuIR高剂量组血清IL-23和IL-17水平明显降低（P<0.01）,滑膜细胞增生与炎症细胞浸润程度明显减轻。结论：nbuIR能改善CIA小鼠局部关节肿胀,下调血清IL-23和IL-17水平,减少滑膜炎症程度,其机制可能与调节IL-23/IL-17轴有关。     

The effect of amifostine, a cytoprotective agent, on paraquat toxicity in mice

Background

Paraquat (PQ) is a highly poisonous herbicide with a variety of toxic effects, most notably pulmonary fibrosis. In alveolar epithelial cells, it is converted to a PQ radical and subsequently generates other reactive species resulting in lipid peroxidation and cell destruction. Amifostine is a thiophosphate prodrug approved by the FDA for the prevention of toxicities associated with cisplatin and therapeutic radiation. When amifostine is converted to an active metabolite (WR-1065), it functions as an oxygen and DNA radical scavenger that has been shown to protect against lipoperoxidation. The aim of this study was to determine whether amifostine improves survival or lung injury resulting from PQ toxicity.

Methods

Swiss mice (n = 23 per group) were given an approximate LD₇₅ dose of PQ intraperitoneal (60 mg/kg). Thirty minutes prior to PQ injection, group 1 was pretreated with 200 mg/kg of amifostine subcutaneously (s.c.). Subsequent doses of amifostine at 75 mg/kg were administered 4 hours after PQ injection, and injections continued every 8 hours for a total of 6 doses (cumulative dose: 575 mg/kg). Four hours after PQ injection, group 2 received 200 mg/kg of amifostine subcutaneously. Subsequent doses of amifostine at 75 mg/kg were administered every 8 hours (cumulative dose: 575 mg/kg). Four hours after PQ injection, group 3 received 100 mg/kg of amifostine subcutaneously. Subsequent doses of amifostine at 30 mg/kg were administered every 8 hours (cumulative dose: 250 mg/kg). Group 4 received equivolume injections of sterile 0.9% saline s.c. at the same time intervals. We removed lungs from all mice for histologic analysis and injury scoring.

Results

The number of surviving mice in groups 1, 2, 3, and 4 were 17, 18, 17, and 17 respectively. The Kaplan-Meier with log rank analysis showed no differences in survival. Lung injury scores did not differ between treatment groups and the control group for either dead or surviving mice.

Conclusion

Amifostine does not appear to improve survival or lung injury due to PQ toxicity at the doses administered.     

肝X受体在百草枯致急性肺损伤小鼠肺组织中的表达及作用

目的研究肝X受体(Liver X receptors,LXRs)在百草枯(Paraquat,PQ)致急性肺损伤小鼠肺组织中的表达情况及保护作用。方法 48只雄性c57小鼠随机分为6组,对照组:0.1 m L生理盐水腹腔注射;A组(TO901317低剂量对照组):5 mg/kg TO901317腹腔注射;B组(TO901317高剂量对照组):20 mg/kg TO901317腹腔注射;C组(百草枯染毒组):百草枯28 mg/kg腹腔注射;D组(TO901317低剂量预处理组):百草枯染毒前0.5 h给予TO901317 5 mg/kg腹腔注射;E组(TO901317高剂量预处理组):百草枯染毒前0.5 h给予TO90131720 mg/kg腹腔注射。在百草枯染毒后72 h处死小鼠,收集肺组织及肺泡灌洗液标本。肺组织取出后测定肺湿重/干重比,肺组织切片后HE染色进行肺损伤评分,采用ELISA方法检测肺泡灌洗液中IL-1β和TNF-α含量,Western blot方法检测肺组织中LXRs(LXRα和LXRβ)及Toll样受体4(TLR-4)的表达。结果对照组小鼠肺组织中可检测到较高水平的LXRα和LXRβ表达,与对照组相比,百草枯中毒组小鼠LXRα和LXRβ表达明显减少,肺湿重/干重比及肺损伤评分显著增加,肺泡灌洗液中IL-1β和TNF-α含量明显增高,TLR-4表达明显增加。上述改变在TO901317预处理组明显减轻,减轻程度与TO901317剂量有关。结论肝X受体可以在正常小鼠肺组织的中表达,百草枯中毒可显著抑制肝X受体在小鼠肺组织中表达,应用LXRs激动剂TO901317能明显减轻百草枯导致的小鼠急性肺损伤程度,这一作用可能与LXRs抑制TLR-4在肺组织中的表达有关。     

盐酸氨溴索对毛细支气管炎小鼠IL-17/STAT3通路及气道高反应的影响

目的 探究盐酸氨溴索对毛细支气管炎小鼠气道高反应性及白细胞介素17(IL-17)/信号传导转录激活因子3(STAT3)通路的影响.方法 采用随机数字表法将72只Balb/c小鼠随机分为对照组、模型组、布地奈德组(20 mg/kg)、盐酸氨溴索高、中、低剂量(60、30、15 mg/kg)组,每组12只.除对照组外,其余...     

螺内酯阻抑百草枯中毒大鼠肺纤维化的机制探讨

目的观察螺内酯能否阻抑百草枯（PQ）中毒大鼠肺纤维化及探讨其可能的作用机制。方法54只雄性SD大鼠随机分为对照组、PQ染毒组（一次性PQ80mg／kg灌胃）和螺内酯干预组（一次性PQ80mg／kg灌胃并予每天1次螺内酯100mg／kg灌胃）。各组大鼠于染毒后第7、14、28天分批处死,取肺组织行HE染色、Masson染色并做肺泡炎、肺纤维化评分,计算肺系数,测血浆及肺组织醛固酮（ALD）含量及肺羟脯氨酸含量,应用免疫组化法测肺组织转化生长因子-β1（TGF-β1）及α-平滑肌肌动蛋白（α—SMA）蛋白的表达。结果染毒组和干预组血浆、肺组织ALD含量均较对照组升高,第14天始差异有统计学意义（P〈0．05）;干预组各时间点大鼠肺泡炎和肺纤维化程度积分、肺系数、肺羟脯氨酸含量均低于染毒组（P〈0．01）;干预组第14天始肺组织TGF—β1、α-SMA蛋白的表达均低于染毒组（P〈0．05或P〈0．01）。结论ALD、TGFβ1、α—SMA可能均参与PQ中毒致肺纤维化的发病进程。螺内酯对PQ中毒大鼠肺纤维化有一定程度的阻抑作用,可能与其抑制ALD受体,并减少肺部TGF-β1和aSMA的表达有关。     

FTY720 attenuates paraquat-induced lung injury in mice

Paraquat (PQ) poisoning, with the lung as a primary target organ, is a devastating disease which irreversibly progresses to diffuse alveolitis followed by extensive lung fibrosis. In the present study, we aimed to investigate the effect of FTY720, an immune modulator, on PQ-induced lung injury in mice. C57BL/6 mice were randomized into four groups: 1) PQ group (n = 12): mice was instilled with PQ (30 mg/kg, ip); 2) PQ + FTY720 group (n = 12): animals received FTY720 (0.1 mg/kg, ip) solution 2 h after PQ exposure and twice a week for 4 consecutive weeks; 3) FTY720 group (n = 5): FTY720 (0.1 mg/kg, ip) was administrated twice a week for 4 consecutive weeks; and 4) Control group (n = 10): same volumes of saline were injected. Mice were sacrificed on either day 3 or day 28 for histopathological, biochemical and immunohistochemical analyses of lung damage indicators. We found that FTY720 treatment attenuated PQ-induced acute lung injury and lung fibrosis as evaluated by histopathological changes and Ashcroft score. On day 3, FTY720 administration reduced PQ-induced increases in lung wet weight/body weight (LW/BW), total protein and cytokine levels including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in bronchoalceolar lavage fluid (BALF). On day 28, the expressions of alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β) and vascular endothelial growth factor (VEGF) detected by immunohistochemistry, as well as the mRNA levels of α-SMA, Type-I Collagen and Type-III Collagen examined by Real-time PCR were down-regulated after FTY720 treatment. These results indicate that FTY720 could attenuate PQ-induced lung injury, but further investigation is necessary.     

白细胞介素32在博来霉素诱导的小鼠肺纤维化组织中的表达及意义

目的 探讨白细胞介素32(IL-32)在博来霉素(BLM)诱导的小鼠肺纤维化过程中各期的表达和意义.方法 将72只雄性小鼠随机分为三组,每组24只.分别给予0.9%氯化钠注射液0.04 ml(C组)和等量的BLM(5 mg/kg)(B、A组),一次性气管内灌注.A组在BLM灌注后每天给予地塞米松5 mg/kg腹腔注射.然后各组分别于第3、7、14和28天各处死6只小鼠,取肺组织,做病理切片、免疫组织化学染色,应用Western blot法测定IL-32表达.结果 B组肺组织病理切片按时间顺序呈现由肺泡炎至纤维化动态改变.B组肺组织中IL-32蛋白表达水平高于C组(P＜0.01)和A组.结论 IL-32在肺纤维化形成过程中高表达,可能在肺纤维化形成的早中期发挥重要作用.     

Berberine regulates pulmonary inflammatory microenvironment and decreases collagen deposition in response to bleomycin-induced pulmonary fibrosis in mice

The purpose of this study was to explore the protective effect and potential mechanism of berberine on bleomycin (BLM)-induced fibrosis after lung injury in conjunction with network pharmacology. Berberine and pulmonary fibrosis prediction targets were collected for Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and so forth. A single intranasal dose of BLM (2.5 mg/kg) was administered to establish a model of fibrosis after lung injury, and berberine (50 mg/kg) was administered intraperitoneally daily for treatment. Network pharmacology results suggested that the mitogen-activated protein kinase (MAPK) signalling pathway may be a potential mechanism of berberine in delaying pulmonary fibrosis. The results of animal experiments showed that compared with the BLM group, after 14 days of berberine treatment, lung inflammatory cell aggregation was reduced and the expression levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-8 and IL-6 were down-regulated in mice (p < 0.05); after 42 days of berberine treatment, the expression levels of transforming growth factor (TGF)-β1, platelet-derived growth factor-AB (PDGF-AB), hydroxyproline (HYP) and α-smooth muscle actin (α-SMA) were significantly down-regulated (p < 0.05), and the expression levels of total p38 MAPKα and p38 MAPKα (pT180/Y182) were down-regulated also (p < 0.05), inhibited collagen production and deposition, and increased the survival rate of mice to 70%. In conclusion, berberine attenuated inflammation mice, inhibited collagen production and showed some anti-pulmonary fibrosis potential in the MAPK signalling pathway.     

Docosahexaenoic acid (DHA) attenuated paraquat induced lung damage in mice

Context: Accumulating evidences have proposed the critical roles of oxidative stress in the etiology of lung injury caused by paraquat (PQ). Docosahexaenoic acid (DHA) is an essential n-3 polyunsaturated fatty acid (PUFA), which has been proved to possess prominent antioxidative and anti-inflammatory effects. Objective: The aim of this study was to evaluate effects of DHA against acute lung injury (ALI) induced by PQ in mice. Materials and methods: Male Kunming mice were randomly divided into three groups: control group, PQ group, and PQ+DHA group (n = 24). The mice of PQ+DHA group received 500 mg/kg bodyweight DHA by gavage daily for consecutive 14 days. On day 8, the mice in PQ and PQ+DHA groups received a single oral dose of 50 mg/kg bodyweight PQ. All the mice were sacrificed on day 15. The myeloperoxidase (MPO) activities, levels of the malondialdehyde (MDA) and glutathione (GSH), and the 4-hydroxynonenal (4-HNE) and MDA modified proteins of lung were investigated. Results: DHA treatment significantly increased the survival rate of mice treated with PQ. Pulmonary MPO activities and MDA contents were elevated in the mice of the PQ group, while the GSH level was reduced. Furthermore, levels of 4-HNE and MDA modified protein in lungs of the PQ group mice were significantly increased. All the above changes were significantly inhibited by DHA pretreatment. Morphological examination revealed that DHA effectively attenuated the hyperemia, edema of ALI induced by PQ. Conclusion: These results demonstrated that DHA could effectively attenuate PQ-induced ALI in mice probably via its antioxidant activity.     

β-连环蛋白在肺纤维化小鼠肺组织中的表达

目的观察β-连环蛋白在肺纤维化模型小鼠肺组织中的表达。方法昆明小鼠40只随机均分成实验组和对照组,气管内分别一次性注入博来霉素5mg/kg(0.04ml)和生理盐水0.04ml。给药后第3、7、14、28天,每组处死小鼠5只,取肺组织做病理切片和HE染色;用碱水解法检测肺组织羟脯氨酸含量,免疫组化法及Western blot检测肺组织中β-连环蛋白表达。结果实验组肺泡炎和肺纤维化程度均明显高于对照组(P<0.05),羟脯氨酸的含量在第7-28天明显高于对照组(P<0.01)。实验组在各时间点肺组织中的β-连环蛋白表达高于对照组(P<0.05);其表达高峰在第14天。结论β-连环蛋白在模型小鼠肺纤维化发生过程中存在高表达。