甘草甜素抑制肺纤维化大鼠肺组织单核细胞趋化蛋白-1的表达

目的: 观察甘草甜素对博来霉素(BLM)诱导的大鼠肺纤维化的干预作用及可能机制。方法: 随机将大鼠分为对照组、肺纤维化模型组、甘草甜素干预组。气管内注入博莱霉素造成动物模型后,于当天开始每天给药,分别于7 、28 d处死,取肺组织,行嗜伊红染色、Masson染色；检测肺组织匀浆中羟脯氨酸(HYP) 的变化; RT-PCR法测肺组织单核细胞趋化因子-1 mRNA的表达,免疫组化测肺组织单核细胞趋化因子-1蛋白的表达。结果: 干预组肺纤维化程度轻于模型组; 肺组织匀浆羟脯氨酸(HYP)含量显著低于模型组( P<0.01) ;在模型组 MCP-1第7 d表达就明显升高，第28 d下降，但仍高于对照组，干预组与模型组有同一规律，但均减弱，第7、28 d与模型组(M组)比较，P<0.05。结论: 甘草甜素能减轻博莱霉素诱导的大鼠肺纤维化，这种作用可能部分是通过抑制MCP-1的表达而实现。     

银杏叶提取物对大鼠肺纤维化初期肺结缔组织生长因子表达的影响

目的：　研究银杏叶提取物（GbE）对博莱霉素(BLM)性肺纤维化初期大鼠肺内结缔组织生长因子(CTGF)表达的影响。方法： 气管内滴注BLM, 用Western blotting法检测肺组织CTGF含量；用氯胺-T法测定肺组织羟脯氨酸含量；用比色法检测血浆丙二醛(MDA)含量。结果： 注BLM后14 d肺组织CTGF含量和出肺血MDA含量， BLM+NS组均分别高于NS组(P<0.05; P<0.01)。注BLM后30 d肺组织羟脯氨酸含量和出肺血MDA含量，BLM+NS组均分别高于NS组(Both P<0.01)。GbE处理可显著缓解上述变化。结论： GbE缓解BLM性肺纤维化初期肺内CTGF上调; GbE的抗氧化损伤作用可能是其缓解CTGF增多的机制之一。     

复方三七饮对博莱霉素致大鼠肺纤维化TGF-β1/Smads信号通路的影响

目的 探讨复方三七饮(CPNG)对博莱霉素(BLM)致大鼠肺纤维化的干预作用及其机制.方法 雄性SD大鼠60只,随机分为6组:正常组、模型组、醋酸泼尼松组、CPNG大、中、小剂量组[CPNG(H、M、L)],每组10只.经气管内注入BLM(5mg/kg)制备大鼠肺纤维化模型.造模第2天,治疗组分别灌服醋酸泼尼松3.33 mg/(kg ·d)、CPNG大、中、小剂量(100、50、25) mg/(kg·d),正常组和模型组大鼠灌服等体积的蒸馏水,1次/d.28 d后处死大鼠,HE染色和Masson染色进行肺组织病理学观察;碱水法测定肺组织中羟脯氨酸(HYP)含量;Western blot法检测TGF-β1、Smad2、Smad7蛋白的表达水平.结果 与模型组大鼠比较,肺组织的病理组织学HE和Masson染色显示CPNG能明显减轻大鼠肺泡炎和肺纤维化程度(P＜0.01);CPNG各剂量组大鼠肺组织中HYP降低(P ＜0.01);CPNG各剂量组TGF-β1、Smad2蛋白的表达水平降低(P＜0.01),Smad7蛋白表达水平升高(P＜0.01).结论 复方三七饮对博莱霉素致大鼠肺纤维化具有一定的防治作用,可能与调节TGF-β1/Smads信号通路有关.     

博来霉素致大鼠肺纤维化模型肺组织的动态病理变化及其发生机制

目的： 了解博来霉素（BLM）致大鼠肺纤维化模型肺组织的动态病理变化,探讨BLM致肺纤维化的作用机制。方法：60只雄性SD大鼠采用随机数字表法分为正常对照组（N组）和肺纤维化模型组（B3、B7、B14、B28、B56组）,每组10只。除N组外,其余各组采用气管内注入BLM致大鼠肺纤维化模型, 分别于3、7、14、28、56 d处死各组大鼠,右肺行苏木精-依红（HE）、Masson胶原及天狼猩红染色,测定左肺羟脯氨酸（HYP）的含量。 RT-PCR法半定量测定转化生长因子-1（TGF-β1）、基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶组织抑制物-1（TIMP-1）mRNA在肺内的表达。免疫组化法观察TGF-β1、MMP-9及TIMP-1蛋白在大鼠肺组织的表达。结果：(1) 模型组大鼠肺组织HYP含量显著高于N组（P<0.05）,模型组大鼠肺组织肺泡炎症的程度也明显重于N组,B14、B28和B56组大鼠肺纤维化的程度明显重于N组,大鼠在灌注BLM后不同时点其肺组织有着不同的病理变化。 (2) TGF-β1、MMP-9及TIMP-1在正常组大鼠肺脏中即有表达,但表达较弱,灌注BLM后它们的表达均增强,不同时点它们在肺组织内的分布有不同的特点。结论：给予后不同时点大鼠肺组织有着不同的病理变化特点,TGF-β1、MMP-9和TIMP-1在BLM诱导的肺纤维化形成过程中起着重要的调节作用。     

Rho激酶-1在肺纤维化小鼠肺组织中的表达变化与上皮-间充质转化

目的 观察Rho激酶-1(Rock-1) 在博莱霉素（BLM）致小鼠肺纤维化中的表达变化, 探讨其在肺纤维化中与上皮间充质细胞转化(EMT) 的关系。 方法 将60只小鼠随机分成正常对照组（Cont组）, BLM致肺纤维化模型组, 地塞米松（DXM）治疗组。BLM组给予0.04ml BLM (5mg/kg)一次性气管内灌注,治疗组在BLM一次性气管内灌注后每天给予DXM 5mg/kg腹腔注射。各组分别于第3、7、14和28天各处死5只小鼠, 取肺组织, 做病理切片,HE染色观察小鼠肺炎症和纤维化的程度, 以样本碱水解法检测肺组织中羟脯氨酸(HYP)含量, 免疫组织化学检测不同实验组小鼠间充质细胞标记物α-平滑肌肌动蛋白(α-SMA) 和上皮细胞标记物上皮钙黏素( E-Cad) 的表达,应用Western blotting法测定不同实验组小鼠Rock-1的表达水平。 结果 BLM组肺组织病理切片按时间顺序呈现由肺泡炎至纤维化的动态改变,肺组织胶原含量在第7天明显增加, 第28天达高峰, HYP含量测定动态增高。与Cont组比较、BLM组、DXM组E-Cad的蛋白表达降低,α-SMA蛋白表达增高。Western blotting结果显示,BLM组Rock-1的表达与正常对照组比较显著增高( P<0.05),第14天时达到高峰。DXM组Rock-1的表达逐步下降。 结论 Rock-1在小鼠肺纤维化中表达增高, 表明其可能是肺纤维化形成的促进因子, 且随着Rock-1的增高,α-SMA逐步增高 E-Cad逐步降低, 推测Rock-1在肺纤维化形成中的机制可能与促进EMT有关。     

甘草酸对博莱霉素诱导的实验性肺纤维化的干预作用

目的:探讨甘草酸(GA)对博莱霉素(BLM)诱导的小鼠肺纤维化的干预作用及其可能机制。方法:将160只雄性C57BL/6J小鼠随机分为生理盐水(NS)组、BLM组、BLM+NS组和BLM+GA组。通过口咽气管吸入法吸入博莱霉素(2.5 mg/kg)建立实验性肺纤维化模型,BLM+GA组及BLM+NS组每天给予40 mg/kg甘草酸或等体积的生理盐水灌胃,于术后第3、7、14、21天取材。采用HE染色和Masson染色观察肺组织病理学变化及纤维化程度,采用流式细胞术检测循环单核细胞和肺泡巨噬细胞的亚群比例变化,采用RT-qPCR检测肺组织中转化生长因子β1(TGF-β1)mRNA的表达水平,采用碱水解法检测肺组织中羟脯氨酸(HYP)含量。结果:与NS组相比,BLM组和BLM+NS组肺组织的炎症浸润及胶原含量明显增多,实验性肺纤维化模型制备成功。与BLM+NS组相比:BLM+GA组肺组织的炎症细胞浸润及胶原纤维沉积较少;第3、7天的Ly6C~(hi)单核细胞亚群比例和第7、14天肺泡巨噬细胞M2表型比例显著降低(P0.01);肺组织TGF-β1 mRNA表达量和HYP含量显著降低(P0.01)。结论:GA可以减轻博莱霉素诱导的小鼠肺组织的炎症反应和胶原纤维沉积,可能与GA对单核巨噬细胞的表型偏移和调控以及肺组织TGF-β1的表达下调有关。     

结缔组织生长因子在大鼠肺纤维化模型中的蛋白表达

目的 :了解结缔组织生长因子 (connectivetissuegrowthfactor ,CT GF)在大鼠肺纤维化模型中的表达状况及其与肺纤维化之间的关系。方法 :42只Wistar大鼠随机分为二组。模型组 (M组 ) :气管内灌注博莱霉素 ,对照组 (C组 ) :气管内灌注生理盐水。于灌注后第 7、14、2 8天每组分别处死大鼠 7只。制备大鼠肺组织切片。用免疫组化SABC法分别检测二组大鼠肺组织中CTGF及转化生长因子 β1 (TGF β1 )、纤维连接蛋白 (FN )在肺内的表达水平。结果 :M组CTGF及TGF β1 、FN在肺内的表达水平在各时间点均显著高于C组 (P <0 .0 5 )。结论 :CTGF作为TGFβ1 的下游因子 ,可能通过促进细胞外基质(ECM)如FN和胶原蛋白等合成而在博莱霉素诱导的肺纤维化形成过程中起重要作用     

丙戊酸钠减轻博莱霉素致大鼠肺纤维化

目的:探讨丙戊酸钠在博莱霉素诱导的肺纤维化中的作用及机制。方法:42只大鼠随机分为正常对照组、模型组和治疗组。造模采用博来霉素5 mg/kg气管内注射,自造模14 d开始分别采用生理盐水(0.5m L/d)、丙戊酸钠(300 mg·kg-1·d-1)和地塞米松(0.6 mg·kg-1·d-1)腹腔内注射治疗14 d。模型组分别在造模后14和、28 d处死。治疗组在造模后28 d处死。然后通过HE染色、Masson染色、羟脯氨酸(HYP)检测和Western blotting检测α-平滑肌肌动蛋白(α-SMA)及E-钙黏蛋白(E-cadherin)表达的变化,综合分析丙戊酸钠对肺纤维化发展的干预作用。结果:HE染色显示丙戊酸钠治疗组的肺泡结构、肺间质的形态优于生理盐水组和地塞米松治疗组。Masson染色及HYP检测用于衡量肺组织内胶原的分布及含量,可见丙戊酸钠治疗组肺组织内胶原的分布及含量均显著低于地塞米松治疗组及生理盐水组。丙戊酸钠可以降低α-SMA的表达,同时上调上皮标志性蛋白E-cadherin的表达。结论:丙戊酸钠可以通过减少胶原的表达与分布及下调间充质蛋白α-SMA,同时上调上皮蛋白E-cadherin的表达从而减轻博来霉素诱导大鼠肺纤维化。     

依那西普对博莱霉素所致小鼠肺纤维化的影响及其机制

目的:观察依那西普对博莱霉素诱导的小鼠肺纤维化的作用及可能机制。方法:方法将30只SPF级雄性昆明小鼠随机分为3组,即对照组、模型组、干预组,每组10只。对照组小鼠气管内灌注生理盐水,模型组小鼠气管内灌注博莱霉素5 mg/kg,干预组小鼠气管内灌注博莱霉素后,3 mg/kg依那西普腹腔注射,一周2次。于造模后28 d处死小鼠,收集肺组织,碱水解法检测羟脯氨酸含量;肺组织用4%多聚甲醛固定后,石蜡包埋切片,行HE染色及Masson染色;Western blot法检测肺组织NF-κB和磷酸化NF-κB的表达。结果:干预组小鼠肺组织羟脯氨酸含量较模型组明显下降(P0.01);干预组肺组织炎症评分较模型组明显下降(P0.01),肺纤维化评分较模型组下降(P0.01);干预组肺组织磷酸化NF-κB的表达下降(P0.01)。结论:依那西普可抑制NF-κB的磷酸化,减轻博莱霉素导致的小鼠肺部炎症程度和纤维化改变,延缓肺纤维化进展。     

骨桥蛋白单抗抑制大鼠肺纤维化的研究

探讨骨桥蛋白(osteopontin,OPN)对博莱霉素(bleomycin,BLM)诱导的大鼠肺纤维化肺组织基质金属蛋白酶-9(MMP-9)、金属基质蛋白酶抑制剂-1(TIMP-1)和Ⅰ、Ⅲ型胶原mRNA表达的影响。取72只健康雌性Wistar大鼠随机分成生理盐水对照组(NS组)、博莱霉素模型组(BLM组)和骨桥蛋白抗体干预组(OPN-Ab组)各24只,气管内灌注BLM复制肺纤维化模型(BLM组、OPN-Ab干预组),NS组气管内灌注生理盐水,OPN-Ab组于0d、2d、4d、6d尾静脉注射骨桥蛋白抗体(1:32),BLM组和NS组尾静脉注射生理盐水,各组分别于7d、14d、28d处死动物8只。收集肺组织作切片行HE、MASSON染色测定肺泡炎症和纤维化改变,免疫组织化学PAP法测定肺组织中OPN、MMP-9、TIMP-1的表达;RT-PCR测定肺组织Ⅰ/Ⅲ型胶原mRNA的表达。结果与BLM组比较,在第7天和第14天OPN-Ab组肺泡炎明显减轻(P0.01);而肺纤维化程度在各时间点均明显减轻(P0.05);与NS组比较,BLM组、OPN-Ab组肺组织中OPN、MMP-9、TIMP-1表达水平均显著升高(P0.01)。BLM组第7天OPN、MMP-9、TIMP-1在肺组织中表达水平显著升高,随后下降,第28天时仍高于NS组(P0.01)。与BLM组比较,OPN-Ab组各时间点OPN、MMP-9、TIMP-1表达水平降低(P0.01)。OPN-Ab组第7、14、28天肺组织Ⅰ、Ⅲ型胶原mRNA表达均较同时间点BLM组明显降低(P0.05)。OPN可能是肺纤维化形成机制中的重要因素,骨桥蛋白抗体可能通过抑制细胞因子MMP-9、TIMP-1表达,减少肺组织中胶原的生成,最终抑制肺纤维化。     

Bleomycin-induced pulmonary fibrosis in rat is associated with increased expression of collagen-binding heat shock protein (HSP) 47

 Increased accumulation of collagens in extracellular matrix (ECM) is mainly responsible for bleomycin-induced pulmonary fibrosis in rats. This study was designed to assess whether increased collagen accumulation in bleomycin-induced pulmonary fibrosis is associated with heat shock protein (HSP) 47, a molecular chaperone for collagen biosynthesis. We investigated the expression of type I and type III collagens and HSP47 in bleomycin-induced pulmonary fibrosis. Fifteen male Wistar rats were divided into two groups; group I: bleomycin-induced pulmonary fibrosis; group II: PBS-treated age-matched control rats. Pulmonary fibrosis was induced by injecting a single dose of bleomycin sulphate (5 U/kg body weight) intratracheally. Three bleomycin-treated rats and two age-matched control rats were sacrificed at the end of each of the 1st, 2nd and 4th weeks of the experiment. In bleomycin-treated rats, histological examination revealed pulmonary fibrosis, which increased with time. Increased type I and type III collagen desposition was observed in the lungs of all the bleomycin-treated rats. Weak immunostaining of HSP47 was noted in the control lungs. In contrast, strong immunostaining for HSP47 was seen in all the bleomycin-treated fibrotic lungs. In addition, increased numbers of phenotypically altered myofibroblasts (α-smooth muscle actin immunopositive) and fibroblast (vimentin immunopositive) were seen in bleomycin-treated lungs and found to express HSP47. Parallel increase of collagens and their molecular chaperone HSP47 expression was found in the bleomycin-treated lungs, and their co-localization could be detected by double immunostaining. Overexpression of HSP47 may play a significant part in the excessive assembly of collagens and could contribute in this way to the fibrosis found in bleomycin-treated rat lungs. Received: 30 April 1997 / Accepted: 17 July 1997     

大黄酸通过抑制miR-21而干预TGF-β1/Smad通路并减轻博莱霉素所致大鼠肺纤维化

目的:观察大黄酸(rhein,RH)对博莱霉素所致肺纤维化大鼠微小RNA-21(miR-21)表达以及转化生长因子β1(TGF-β1)/Smad通路的影响。方法:博莱霉素一次性气管内注射复制大鼠肺纤维化模型,随机分为RH低、中、高剂量组及模型(model)组;正常对照组大鼠气管内注射生理盐水。用药28 d后,HE染色观察各组大鼠肺组织形态学的变化;测定肺系数、肺组织羟脯氨酸含量;real-time PCR检测肺组织中miR-21和TGF-β1/Smad7m RNA表达;Western blot法分析TGF-β1和Smad7蛋白的表达。结果:与model组相比,RH用药组大鼠的肺泡炎及肺纤维化程度有明显降低,肺系数及肺组织羟脯氨酸含量也显著减少,肺组织中miR-21表达下降,TGF-β1的m RNA和蛋白表达水平也明显下降,Smad7的mRNA及蛋白表达水平明显增高(P0.05)。结论:RH抗肺纤维化的作用可能与抑制miR-21的表达,从而干预TGF-β1/Smad信号通路,减少细胞外基质沉积有关。     

丹参素干预对肺纤维化大鼠TGF-β1/Smads信号通路的影响

 目的： 探讨丹参素对博莱霉素所致大鼠肺纤维化的防治作用及其可能机制。方法： SD大鼠经气管内滴注博莱霉素诱导肺间质纤维化,随后分别腹腔内注射丹参素15 mg·kg-1·d-1(DA组)、地塞米松1 mg·kg-1·d-1(DXM组)和生理盐水2 mL·d-1 (BLM组)进行干预,正常对照组(NC组)气管内滴注和腹腔内注射均用生理盐水。于造模后第28天处死所有大鼠,通过苏木精-伊红(HE)染色和Masson染色来评价治疗效果;免疫组化技术检测肺组织α-平滑肌肌动蛋白(α-SMA)表达;实时荧光定量PCR测定转化生长因子β1（TGF-β1）、Smad3及Smad7 mRNA的表达。结果： DA组与BLM组相比,肺泡炎症及肺纤维化程度均明显减轻,肺组织α-SMA表达明显减少,肺组织TGF-β1和Smad3 mRNA表达明显减少,Smad7 mRNA明显增多。结论： 丹参素早期应用可减轻博来霉素诱导的大鼠肺纤维化,可能通过抑制TGF-β1、Smad3 mRNA和促进Smad7 mRNA的表达而实现。     

Perinatal expression of HSP70 and VEGF in neonatal rat lung vessels exposed to nicotine during gestation

We assessed the influence of maternal nicotine exposure during gestation on perinatal expression of HSP70 and VEGF in rat lung parenchyma and lung vessels. Adult white Sprague-Dawley virgin rats were mated with adult male rats over 2 days, with two females for every male. After confirming pregnancy, 30 gravid rats (dams) were then randomly assigned to two equal groups (one experimental and one control; n=15 in each). Experimental dams were treated with subcutaneus (s.c.) (-)-nicotine tartrate, 3 mg/kg body weight/day, during pregnancy from gestational days 9 through 21. After sacrifice, lungs were removed en bloc and formalin-fixed, and paraffinembedded tissue sections were evaluated by immunohistochemistry using a three-step streptavidin-biotin-peroxidase method with monoclonal antibodies directed against HSP70 or VEGF. HSP70 and VEGF expression was increased in the vascular smooth muscle cells of the experimental group (t1) compared to the control group (t(2))t(1)=7.593, t(2)=4.666, p<0.05). The number of bronchioles that stained positively with HSP70 was higher in the nicotineexposed group than in the control group (t(1)=9.274, t(2)=6.956, p<0.05). In conclusion, gestational nicotine exposure increased the expression of VEGF and HSP70 in rat lung parenchyma, especially in the airway epithelium and vascular smooth muscle cells. In vascular smooth muscle cells, these molecules may contribute to nicotine-related hypoxic pulmonary hypertension.     

布地奈德对肺纤维化大鼠Smad4、PDGF-A及PAI-1表达的影响

目的:探讨布地奈德(BUD)对肺纤维化大鼠肺组织转化生长因子-β1(TGF-β1)、血小板衍化生长因子-A(PDGF-A)、抗生物皮肤生长因子同源物4母体(Smad4)、纤溶酶原激活物抑制物-1(PAI-1)表达的影响。方法:取健康雌性Wistar大鼠随机分成博莱霉素(BLM)组、生理盐水(NS)组和BUD组,每组15只。NS组气管内灌注NS,BUD组、BLM组气管内灌注BLM,继之0～6 d每天雾化1次,BLM组和NS组雾化吸入NS,BUD组雾化吸入BUD,分别于第7、14、28天处死3组大鼠各5只。用HE、Masson染色观察肺泡炎症和纤维化改变;免疫组化法测定肺组织中TGF-β1、PDGF-A、Smad4、PAI-1的表达。结果:第7、14天,BUD组肺泡炎程度较BLM组减轻(P<0.05);第7、14、28天,BUD组肺纤维化程度均较BLM组减轻(P<0.05)。第7、14、28天,BUD组肺组织中TGF-β1、PDGF-A、Smad4、PAI-1表达较BLM组明显降低(P<0.05)。结论:BUD雾化吸入可降低肺纤维化大鼠肺组织TGF-β1、PDGF-A、Smad4、PAI-1的表达,同时亦可减轻其肺泡炎及肺纤维化程度。     

Immunomodulation of experimental pulmonary fibrosis by intravenous immunoglobulin (IVIG)

OBJECTIVES: To assess the immunomodulatory effect of intravenous immunoglobulin (IVIG) using an experimental model of bleomycin-induced pulmonary fibrosis. METHODS: Pulmonary fibrosis was induced in C57BL/6 mice by direct intratracheal injection of bleomycin. Mice were treated with IVIG 1 week prior to (prevention protocol), or 10 days following bleomycin injection, when the disease was in progress. The controls used in the study included mice given phosphate buffered saline (PBS) and mice subjected to a commercial individual-IgG. Collagen-I deposits in the affected lungs were detected by Sirius red staining of paraffin embedded lung sections. The collagen-I content was measured by employing the hydroxyproline assay. RESULTS: Prevention of bleomycin-induced pulmonary fibrosis by IVIG has been demonstrated by reduced expression of collagen-I protein in the affected lungs. The hydroxyproline levels in the lungs of the IVIG-treated mice were 214.33 +/- 13.56 microg/1 g tissue, compared to the higher levels in lungs of IgG treated mice (342.44 +/- 35.60 microg/1 g tissue) or untreated controls 328.00 +/- 45.55 microg/1 g tissue, (p < 0.0001). Effective treatment of bleomycin-induced pulmonary fibrosis by IVIG has been demonstrated by the reduced expression of collagen-I protein in the affected lungs, detected by sirius red histological staining. The hydroxyproline levels in the lungs of the IVIG-treated mice were 261.00 +/- 18.81 microg/1 g tissue, in comparison to the higher levels in the lungs of the IgG treated mice (342.43 +/- 32.89 microg/1 g tissue) and of untreated controls (344.33 +/- 49.85 microg/1 g tissue), (p < 0.001). CONCLUSIONS: Based on these preliminary studies, we conclude that IVIG may have a beneficial effect in the down regulation of collagen-I levels in the lungs of mice with bleomycin-induced pulmonary fibrosis.     

结缔组织生长因子在博莱霉素诱导的小鼠肺纤维化中的作用探讨

目的:检测结缔组织生长因子(CTGF)在小鼠肺内的表达,并探讨其在肺纤维化中的意义。方法:通过向气管内滴入博莱霉素建立小鼠肺纤维化模型。用免疫组化染色方法检测不同时期肺组织中CTGF蛋白的表达;用RT PCR检测CTGFmRNA的表达;用酸水解法测定肺羟脯氨酸的含量。结果:在正常小鼠肺组织中,CTGF蛋白和其mRNA几乎不表达;而在模型组的肺组织中表达明显升高(P<0.01)。CTGF蛋白表达于支气管/细支气管上皮细胞、肺泡Ⅱ型上皮细胞和肺成纤维细胞,表达量与肺组织中羟脯氨酸的含量呈显著的正相关(r=0.92,P<0.001)。结论:CTGF与肺纤维化的形成关系密切,CTGF检测可作为评价肺纤维化发生、发展的一种灵敏的指标。     

Geranylgeranylacetone, a noninvasive heat shock protein inducer, induces protein kinase C and leads to neuroprotection against cerebral infarction in rats

Previous studies demonstrated the cytoprotective effect of geranylgeranylacetone (GGA), a heat shock protein (HSP) inducer, against ischemic insult. Protein kinase C (PKC) is thought to be an important factor that mediates the expression of heat shock protein 70 (HSP70) in vitro. However, the signaling pathways in the brain in vivo after oral GGA administration remain unclear. We measured and compared infarction volumes to investigate the effect of GGA on cerebral infarction induced by permanent middle cerebral artery (MCA) occlusion in rats. To clarify the relationship between PKC induction and HSP70 expression, we determined the amounts of HSP70 and PKC proteins after GGA administration by immunoblotting. We evaluated the effects of pretreatment with chelerythrine (CHE), a specific PKC inhibitor, on expressions of PKC and HSP70 proteins with immunoblotting. Neuroprotective effects of GGA (pretreatment with a single oral GGA dose (800 mg/kg) 48 h before ischemia) were prevented by CHE pretreatment, which indicates that PKC may mediate the GGA-dependent protection. Oral GGA-induced HSP70 expression induced PKC delta, and GGA pretreatment enhanced ischemia-induced HSP70, both of which were prevented by CHE pretreatment. These results suggest that a single oral dose of GGA induces PKC delta and promotes HSP70 expression in the brain and that GGA plays an important role in neuroprotection against cerebral ischemia.     

谷氨酰胺对脂多糖血症大鼠热休克蛋白70和肿瘤坏死因子-α表达的影响

目的：观察谷氨酰胺对脂多糖血症大鼠热休克蛋白70和肿瘤坏死因子-α的影响。 方法: 将大鼠分为脂多糖组（LPS）、谷氨酰胺组（Gln）和对照组(C)。各组动物均在给予LPS前（对照组在给予生理盐水）和后2、4、6 h采血。用放射免疫法测定血浆肿瘤坏死因子-α（TNF-α）含量。于术后6 h处死，取肺、肝、肠组织，采用SABC方法，免疫组织化学染色进行HSP70检测，并HE染色，观察组织变化。 结果： 注射LPS后2 h，LPS组血浆TNF-α表达显著升高（P<0.01），Gln可显著抑制其升高（P<0.01）。而注射LPS后4、6 h，两组血浆TNF-α浓度没有明显差异。LPS组肺、肝、肠组织的HSP70灰度值分别为（107.94±10.96）、（120.04±5.73）和（123.31±14.81）。Gln组的HSP70灰度值显著降低，分别为（89.71±9.64）、（89.38±12.03）和（107.61±14.02）（均P<0.05）。病理学观察显示, Gln组肺、肝、肠组织损伤程度比LPS组轻。 结论： 谷氨酰胺可提高热休克蛋白70的表达，对脂多糖血症大鼠有防治作用。