Minor role of lipid peroxidation in acute bleomycin toxicity in rats

Summary Bleomycin was injected i.p. in rats, and the amount of expired ethane which indicateds lipid peroxidation was followed up for 78 h. Compared to controls neither 1x30 mg/kg and 2x30 mg/kg nor 1x70 mg/kg bleomycin led to increased ethane expiration, although body weight loss indicated toxicity. That pulmonary toxicity had been developed due to the acute bleomycin treatment could be demonstrated by histological examinations of lungs of the animals of the highest dosage group.The combined treatment of rats with bleomycin and ferrous ions neither resulted in an increase of ethane expired compared to that of the ferrous iontreated animals. Rather a decrease was observed.Our results indicate that acute bleomycin toxicity is not associated with increased lipid peroxidation. Furthermore, our data suggest that the bleomycin-ferrous-complex does not initiate lipid peroxidation in vivo.Supported by grants from the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, and the Chem.-Pharm. Fabrik H. Mack, Illertissen (FRG)     

Antileukinate,a hexapeptide inhibitor of CXC-chemokine receptor,suppresses bleomycin-induced acute lung injury in mice

Abstract A hexapeptide, Ac-RRWWCR-NH₂ (Antileukinate), has been reported to be a potent inhibitor of CXC-chemokine receptor. However, the in vivo anti-inflammatory activity of this agent has not been tested except in a rabbit skin edema model. This study was undertaken to investigate the effect of subcutaneously administered Antileukinate on experimental bleomycin-induced acute lung injury in mice, in which CXC-chemokines have been reported to be involved. Lung injury was assessed on the basis of histopathology, the number of total cells, the percentage of neutrophils, and protein concentration in the bronchoalveolar lavage (BAL) fluid, and the wet lung weight at 7 days after intratracheal instillation of bleomycin. Histopathological studies revealed that treatment with Antileukinate markedly suppressed inflammatory cell infiltration and interstitial lung edema. The neutrophil counts in the BAL fluid were significantly decreased in the Antileukinate-treated group. The suppression of pulmonary edema was further confirmed by the reduction of wet lung weight and total protein concentration in the BAL fluid. These findings suggest that Antileukinate is able to inhibit acute lung injury by suppressing neutrophil mobilization induced by CXC-chemokines.     

三氧化二砷对大鼠肺纤维化模型的干预作用及其机制的探讨

目的观察三氧化二砷(arsenictrioxide,AS2O3)对博莱霉素-A5(bleomycin-A5,BLM-A5)所致大鼠肺纤维化有无治疗作用并探讨其作用机制。方法50只SD大鼠分为空白对照组、肺纤维化模型组和三氧化二砷治疗组。其中对照组10只,气管内给予生理盐水后,连续7天腹腔内注入生理盐水;模型组20只,气管内给予BLM-A5后,连续7天腹腔内注入生理盐水;治疗组20只,气管内给予BLM-A5后连续7天腹腔内注入AS2O3。每组再随机均分成2个亚组,分别于实验第7天、第28天处死。检测以下项目:①支气管肺泡灌洗液(bronchoalveolarlavagefluid,BALF)经流式细胞仪行细胞分类和炎性细胞凋亡率检测;②ELISA法检测BALF中细胞因子γ-干扰素(interferon-gamma,IFN-γ)的含量。③光镜下观察肺组织肺泡炎和肺纤维化程度;④实验第28天肺组织羟脯氨酸(hydroxyproline,HYP)含量的测定。结果与模型组相比,治疗组:①BALF中中性粒细胞和淋巴细胞百分比总和降低(P<0.05);炎性细胞凋亡率增加(P<0.05);实验第7天组IFN-γ含量降低(P<0.05)。②肺组织炎症和纤维化程度减轻;HYP含量降低(P<0.05)。结论AS2O3能减轻BLM-A5诱导的肺纤维化大鼠肺组织炎症和纤维化程度,作用机制可能与其诱导肺内炎性细胞凋亡有关。     

白藜芦醇抑制基质金属蛋白酶抗酒精性心肌纤维化

目的探索白藜芦醇对酒精诱导的心肌纤维化的作用及其分子机制。方法将雄性SD大鼠随机分为对照组、酒精组和酒精+白藜芦醇组,每组10只大鼠,干预6个月后取心肌行常规石蜡切片和Masson染色评估心肌纤维化,采用冰冻切片和免疫荧光法检测纤连蛋白的表达,采用免疫印迹法检测心肌组织中基质金属蛋白酶2和基质金属蛋白酶9的表达。结果 6个月酒精摄入可显著增加心肌间质纤维化并明显破坏纤连蛋白的结构,白藜芦醇能显著削弱酒精诱导的心肌纤维化和纤连蛋白破坏。酒精摄入可显著增加心肌组织中基质金属蛋白酶2和基质金属蛋白酶9的表达水平,而白藜芦醇能显著抑制基质金属蛋白酶2和基质金属蛋白酶9的表达水平。结论白藜芦醇能通过抑制基质金属蛋白酶2和基质金属蛋白酶9的表达来抗酒精诱导的心肌纤维化。     

氨基胍在实验大鼠肺纤维化中的作用及机制初探

目的 初步探讨氨基胍(aminoguanidine,AG)在博莱霉素(bleomycin,BLM)诱导的大鼠肺纤维化模型中的作用及其机制.方法 实验第1天将48只SD大鼠随机分为8组:正常对照组、BLM模型组、AG干预组及AG对照组(包括低、中、高3个剂量组),每组6只,经气道滴入BLM/生理盐水后,于实验第2天开始按低、中、高3个剂量给予AG,2周后处死所有大鼠,收集标本.利用Masson染色,观察肺组织纤维化的情况,并进行纤维化评分;利用碱性水解法测定肺组织中羟脯氨酸的含量;利用RT-PCR的方法测定肺组织中热休克蛋白47的基因表达.结果 AG干预组与BLM模型组相比较,前者的纤维化程度均有所减轻,且呈现出剂量依赖性,尤其在中、高剂量组,纤维化评分、羟脯氨酸含量、热休克蛋白47的基因表达出现明显下降(P值均＜0.01).AG对照组与正常对照组比较差异无统计学意义.结论 AG能有效降低BLM诱导的肺纤维化程度,其机制可能与下调热休克蛋白47等纤维化因子的表达有关.     

白三烯抑制剂对博莱霉素所致大鼠肺纤维化的干预作用

目的 观察白三烯抑制剂(LT-S)齐留通对博莱霉素(BLM)所致大鼠肺纤维化模型肺纤维化形成过程的影响.方法 54只SD雄性大鼠随机分为正常组(C组)、模型对照组(M组)和LT-S组(S组)3组,每组18只.S组于气管内滴注BLM(5 mg/kg)诱导肺纤维化,于造模当天开始每日给予齐留通100 mg/kg灌胃;M组以生理盐水代替齐留通灌胃;C组均用生理盐水代替BLM和齐留通.各组动物均于制模后的第7天、第14天和第28天分别随机处死6只动物,分取肺组织行病理切片苏木精-伊红染色和Masson染色观察肺泡炎和肺纤维化程度、碱水解法检测肺组织羟脯氨酸(Hyp)浓度、免疫组织化学技术检测肺组织α平滑肌肌动蛋白(α-SMA)和转化生长因子β1(TGF-β1)水平.结果 S组肺泡炎和肺纤维化程度及肺组织Hyp含量均显著低于M组,其TGF-β1和α-SMA在肺组织中的表达水平亦均显著低于M组.结论 LT-S可减轻BLM诱导的大鼠肺纤维化,并可能通过抑制TGF-β1蛋白表达而实现对成纤维原细胞增殖的抑制.     

库普弗细胞在大鼠酒精性肝病发病机理中的作用

目的:研究库普弗细胞(KC)在酒精性肝病发病机理中的作用.方法:50只雄性wistar大鼠随机分为模型组(40只)和正常对照组(10只),模型组给予乙醇灌胃以建立大鼠酒精性肝病模型,分别于4周、8周、12周和16周处死大鼠,留取血清及肝组织,检测血清IL-1β、IL-6和TNF-α,检测肝匀浆ORF、ASOA、SOD及MDA含量,应用HE染色和苏丹Ⅳ染色观察肝组织病理形态,应用DPAS染色和流式细胞仪观察肝组织KC形态及数量变化.结果:随着造模时间的延长,肝细胞脂肪变性加重,乙醇灌胃16周大鼠肝脏呈现弥漫性小泡性肝细胞脂肪变、灶性坏死,流式细胞仪和DPAS染色显示肝组织KC数量明显增多,血清IL-1β、IL-6和TNF-α水平升高,KC荧光标记率与肝匀浆ORF、MDA呈正相关(相关系数分别为0.76和0.74,均P＜0.01),与ASOA、SOD呈负相关(相关系数分别为-0.72和-O.66,均P＜0.01).结论:KC和致炎类细胞因子增多在酒精性肝病发病过程中发挥着重要作用.     

Preventive effect of melatonin on bleomycin-induced lung fibrosis in rats

Oxidative stress has an important role in the pathogenesis of idiopathic pulmonary fibrosis. Melatonin has direct and indirect free radical-detoxifying activity. The present study investigated whether melatonin treatment attenuates bleomycin-induced lung fibrosis in rats. A group of rats was given one dose of bleomycin while the control animals were given saline. The first dose of melatonin (4 mg/kg/day) was given 2 days before the bleomycin injection. At day 14, fibrotic changes were evaluated using Aschoft's criteria and lung hydroxyproline content. Bleomycin produced a 2.7-fold rise in the fibrosis score that was decreased 65% by melatonin (P < 0.05) and a 1.4-fold increase in hydroxyproline content which was completely prevented by melatonin. Protein carbonyl and thiobarbituric acid reactive substances levels, which were significantly elevated in the bleomycin treated rats, were significantly attenuated by melatonin. Bleomycin administration significantly reduced the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissue. The reduction in CAT activity was prevented by melatonin but SOD and GSH-Px were not influenced. These results revealed that melatonin may prevent the development of bleomycin-induced lung fibrosis via the repression of protein and lipid peroxidation.     

白藜芦醇对慢性心力衰竭患者脂联素及细胞因子的影响

目的:评价白藜芦醇对慢性心力衰竭(CHF)患者血清脂联素及C反应蛋白(CRP)、可溶性细胞间黏附分子-1 (sICAM-1)和白介素6(IL-6)水平的影响。方法:2003年1月-2003年8月长治市人民医院心内科将60例CHF患者随机分成两组,常规CHF组(30例)接受常规治疗,白藜芦醇组(30例)在常规治疗基础上加用白藜芦醇2 mg,2次／日;另设15例健康人作对照(正常对照组)。所有CHF患者治疗前后均测定左心室舒张未期内径(LVDd)、左心室收缩未期内径(LVDs)和左心室射血分数(LVEF)、脂联素、sICAM-1、CRP、IL-6等指标。结果:①CHF患者脂联素水平较健康人降低,sICAM、IL-6与CRP水平增加,彼此之间紧密联系。②脂联素与sICAM-1、IL-6和CRP均呈负相关(r=-0．43,-0．51,-0．47,P<0．05);CRP与sICAM-1及IL-6三者之间均呈正相关(r=0．63,0．53,0．54,P均<0．01)。③白藜芦醇组治疗2个月后与对正常照组比较脂联素水平提高,sICAM-1、IL-6和CRP水平降低(P<0．01),改善左心室射血分数优于常规CHF组(P<0．01)。结论:白藜芦醇可改善CHF患者的心功能,明显升高CHF患者血清脂联素及显著降低CRP、sICAM-1和IL-6水平。     

缬沙坦对肺纤维化模型的干预作用及其对肝细胞生长因子表达的影响

目的研究血管紧张素Ⅱ受体拮抗剂缬沙坦对肺纤维化模型的干预作用及其可能的机制。方法60只Wistar大鼠采用随机数字表法随机分成3组,每组20只:(1)缬沙坦组,经气管插管灌注博莱霉素(BLM)诱导肺纤维化,随后每日用缬沙坦16mg/kg灌胃进行干预;(2)模型组,气管内灌注用BLM,灌胃用生理盐水;(3)对照组,气管内灌注和灌胃均用生理盐水。各组动物于气管内灌注后第7、14、28、42天分别处死5只。取肺组织经苏木精-伊红、Masson胶原染色及测定羟脯氨酸浓度来评价治疗效果。用免疫组化及原位杂交方法分别检测转化生长因子β(TGF-β)蛋白和肝细胞生长因子(HGF)mRNA在肺内的表达。用酶联免疫吸附测定(ELISA)法检测HGF蛋白在大鼠肺组织的含量。结果缬沙坦组肺泡炎程度在第14、28、42天分别为(0·88±0·12)、(0·79±0·21)、(0·75±0·17)分,低于同期模型组的(2·05±0·25)、(1·38±0·12)、(1·19±0·11)分,差异均有统计学意义(P均<0·01);缬沙坦组肺纤维化程度在第7、28、42天分别为(0·28±0·03)、(1·74±0·18)、(1·91±0·09)分,也低于同期模型组的(0·45±0·10)、(2·08±0·32)、(2·77±0·15)分,差异均有统计学意义(P均<0·05);缬沙坦组肺组织羟脯氨酸含量在第14、42天分别为(1·08±0·13)、(1·39±0·20)μg/mg·pro,低于同期模型组的(1·45±0·19)、(2·19±0·37)μg/mg·pro,差异均有统计学意义(P均<0·01);缬沙坦组肺组织中TGF-β蛋白表达在早、晚期分别为2·27±0·30、2·05±0·18,均低于同期模型组的3·99±0·43、2·71±0·46,差异均有统计学意义(P均<0·05)。缬沙坦组HGFmRNA表达在早、晚期分别为1·61±0·20、0·52±0·19,均高于同期模型组的1·98±0·23、0·28±0·14,差异均有统计学意义(P均<0·05);缬沙坦组蛋白含量在早、晚期分别为(203±18)、(129±20)pg/ml,均高于同期模型组的(260±21)、(100±20)pg/ml,差异均有统计学意义(P均<0·05)。结论缬沙坦能减轻BLM诱导的大鼠肺纤维化,有可能通过抑制TGF-β和促进HGFmRNA的表达而实现。     

粒细胞集落刺激因子动员自体骨髓源性细胞对博来霉素致小鼠肺损伤的治疗作用

目的 观察粒细胞集落刺激因子(G-CSF)动员自体骨髓源性细胞(BMDC)对博来霉素所致小鼠肺损伤的修复作用.方法 采用随机数字表法将60只骨髓重建后小鼠分为重建动员组(博来霉素+G-CSF)和重建对照组(博来霉素+生理盐水),每组30只;75只健康小鼠分为未重建动员组30只(博来霉素+G-CSF)、未重建对照组30只(博来霉素+生理盐水)和空白对照组15只(生理盐水+生理盐水).各组分别在实验第3、第7和第14天处死1/3小鼠取材.通过HE染色、Masson胶原染色、肺通透指数和羟脯氨酸含量评价疗效.免疫组织化学方法检测肺组织中转化生长因子-β_1(TGF-β_1)、γ-干扰素、基质金属蛋白酶_9(MMP-9)和金属蛋白酶组织抑制物-1(TIMP-1)的表达;流式细胞仪和激光共聚焦显微镜检测肺组织内BMDC表达.将20只健康小鼠分为观察动员组(博来霉素+G-CSF)和观察对照组(博来霉素+生理盐水),每组10只,不设终点,观察小鼠存活时间.计量资料比较采用t检验(两组间)和单因素方差分析(多组间),组间两两比较采用LSD法;等级资料比较采用Mann-Whitney μ检验(两组间)和Kruskal-Wallis H检验(多组间);采用Kaplan-Meier法进行生存分析.结果 实验第7天,重建动员组肺泡炎程度的平均秩次为15.3,肺间质纤维化程度的阳性面积(×10~3)为46士8,肺羟脯氨酸含量为(O.44±0.09)μg/mg,TGF-β_1、γ-干扰素和MMP-9表达的积分吸光度值(×10~3)分别为111±23、250±72和59±19,均明显低于重建埘照组[28.0、(73±10)×10~3、(0.52±0.07)μg/mg、(161 ±35)×10~3、(299±31)×10~3和(314±77)×10~3];未重建动员组肺泡炎程度的平均秩次为22.7,肺间质纤维化程度的阳性面积(×10~3)为27±15,肺羟脯氨酸含量为(0.41±0.05)μg/mg,肺通透指数为(43.8 ±9.9)×10~(-3),TGF-β_1、γ-干扰素和MMP-9表达的积分吸光度值(×10~3)分别为132±55、178±23和101±54,均明显低于未重建对照组[33.9、(56±13)×10~3、(0.49±0.08)μg/mg、(53.6±8.7)×10~(-3)、(320±98)×10~3、(409±61)×10~3和(288±75)×10~3].重建动员组在第7大肺内BMDC表达的绿色荧光蛋白阳性细胞比例(0.65±0.13)明显高于重建对照组(0.46±0.11).结论 G-CSF动员BMDC对博来霉素所敛肺损伤有一定的保护作用,本实验方法尚不能明显延长小鼠的存活时间.     

白藜芦醇在炎症性肠病中的研究进展

炎症性肠病(IBD)是一类病因不明的肠道慢性非特异性炎症性疾病。白藜芦醇(RSV)是一种提取自红葡萄酒的天然多酚类化合物,其为NAD+依赖的组蛋白去乙酰化酶SIRT1激动剂,具有抗氧化、抗炎、抗肿瘤、抗纤维化等多种生物学活性。RSV在IBD中的作用主要包括抗炎和抗纤维化两个方面,本文就其在IBD中的研究进展作一综述。     

Attenuation by oral N-acetylcysteine of bleomycin-induced lung injury in rats.

Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant balance such as pulmonary fibrosis. This study examines the effect of N-acetylcysteine (NAC) on bleomycin-induced lung fibrosis in rats. NAC (3 mmol x kg(-1); oral) was given daily from 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) or saline, until 14 days postinstillation. NAC partially decreased the augmented collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,354+/-386 and 3,416+/-326 microg x lung(-1) in vehicle-treated and NAC-treated rats, respectively; p < 0.05). The histological assessment using a semiquantitative score showed less collagen deposition and inflammatory cells in NAC-treated rats compared to those receiving bleomycin alone. NAC failed to inhibit the bleomycin-induced increases in lung wet weight and in cell counts and protein levels of bronchoalveolar lavage fluid, but significantly increased total glutathione and taurine levels in bronchoalveolar lavage fluid. These results indicate that oral N-acetylcysteine improves the pulmonary antioxidant protection and may be useful in reducing lung damage produced by bleomycin.     

白藜芦醇对胶原诱导大鼠关节炎的抗炎作用研究

目的 观察白藜芦醇对胶原诱导大鼠关节炎(CIA)的抗炎作用.方法 选择牛Ⅱ型胶原(CⅡ)为免疫原,建立CIA模型.选取42只造模成功的大鼠随机分为7组:模型组;来氟米特(LEF)对照组;白芍总苷(TGP)对照组;甲氨蝶呤(MTX)对照组;白藜芦醇(Res)小剂量组;白藜芦醇中剂量组;白藜芦醇高剂量组.采用关节炎指数评分(AI)法对大鼠关节炎症程度进行评分;采用酶联免疫吸附试验(ELISA)方法测定各组大鼠血清中抗CⅡ抗体水平.结果 AI评分:低剂量白藜芦醇组与模型组比较差异无统计学意义(12.3±0.5与12.8±0.4);高剂量白藜芦醇组低于中、低剂量组(6.0±0.6与8.2±1.0,12.3±0.5,P＜0.01).高剂量白藜芦醇组低于白芍总苷组(6.0±0.6与8.8±0.8,P＜0.01);LEF组低于TGP组、MTX组、3组白藜芦醇组(4.7±0.5与8.9±0.8,6.4+0.5,P＜0.01);血清抗CⅡ抗体水平:模型组明显高于LEF组、MTX组、TGP组及高、中剂量白藜芦醇组(0.928±0.021与0.391±0.016,0.503±0.010,0.525±0.015,0.507±0.01,0.570±0.021,P＜0.01),而与低剂量白藜芦醇组之间差异无统计学意义(0.928±0.021与0.908±0.026);高剂量白藜芦醇组低于白芍总苷组及低剂量白藜芦醇组(0.507±0.01与0.525±0.015,0.908±0.026,P＜0.01);LEF组低于高、中剂量白藜芦醇组(0.391±0.026与0.507±0.010,0.570±0.021,P＜0.01).结论 ①高、中剂量白藜芦醇能够缓解CIA的炎症症状,而低剂量白藜芦醇则无此作用.②中等剂量白藜芦醇对CIA大鼠的短期疗效与TGP相当,高剂量白藜芦醇的疗效强于TGP,但弱于LEF.③白藜芦醇能够抑制血清抗CⅡ抗体的生成.     

Ghrelin ameliorates pancreaticobiliary inflammation and associated remote organ injury in rats

The present study was designed to evaluate whether ghrelin could reduce organ injury and systemic inflammation induced by pancreaticobiliary obstruction. In Sprague-Dawley rats, either the bile duct (BDL) or common pancreaticobiliary duct (PBDL) was ligated or a sham operation was applied. BDL or PBDL rats received either ghrelin (10 ng/kg) or saline intraperitoneally immediately before the surgery and once a day until the rats were decapitated at 72 h. The pancreas, liver, lung and kidney were removed for the histological analysis, and for the determination of malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase activity (MPO). MDA and MPO levels in all the tissues, which were elevated in PBDL group (p < 0.05-0.001), were reversed back to control levels in ghrelin-treated rats. In BDL group, elevations in hepatic MDA and MPO levels (p < 0.001) were also abolished by ghrelin treatment. In contrast to saline-treated group with severe pancreatic damage, ghrelin-treated rats demonstrated a moderate pancreatic and hepatic destruction accompanied with reduced pulmonary and renal damages. The results illustrate that ghrelin protects the hepatic and pancreatic tissues, as well as remote organs against oxidative injury, by a neutrophil-dependent mechanism.     

脂质过氧化在胰腺纤维化形成中的作用

目的研究脂质过氧化对胰腺星状细胞(pancreatic stellate cells,PSC)活化的影响及其在胰腺纤维化形成中的作用。方法实验大鼠每周2次腹腔内注射二乙基二硫代氨基甲酸盐(diethyldithiocarbamate,DDC),共10周建立胰腺纤维化模型。分别于注射后第2,4,6,8,10周处死大鼠,检测胰腺组织中丙二醛(MDA)含量,各时间点胰腺组织α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)的表达,逆转录聚合酶链反应(RT-PCR)检测α1-型胶原(Colα1)、TGF-β1 mRNA水平。结果注射DDC后,胰腺组织内MDA含量逐步升高,8周时高达(6.21±0.70)nmol/mg prot(P<0.01)。4周时可见明显的细胞外基质沉积和纤维化形成,8周时小叶及小叶内广泛纤维化,大量腺体萎缩,形成瘢疤组织。α-SMA、TGF-β1的阳性表达在2周时已出现,4周时明显增加,且阳性细胞多位于胰腺小叶间及腺泡旁纤维化区域。胰腺组织Colα1 mRNA在造模2周时少量表达,4周表达增加,8周后维持在较高水平;对照组TGF-β1mRNA表达水平较低,TGF-β1 mRNA在造模4周时表达明显增强,与对照组相比有显著性差异(P<0.05),6周后表达增加不明显。结论随着造模时间的延长,胰腺组织MDA含量的增加与胶原纤维形成、TGF-β1表达及活化PSC的增加相一致,提示脂质过氧化产物通过激活PSC及刺激TGF-β1的分泌,增加胰腺组织中胶原的沉积,促进胰腺纤维化的形成。     

阿奇霉素对博莱霉素致大鼠肺损伤的干预作用及其机制的探讨

目的从Th1/Th2反应平衡消长的方面探讨肺纤维化的发病机制，并继续探讨阿奇霉素对其的干预作用及机制。方法 雄性Wisar大鼠分为博莱霉素模型组，阿奇霉素治疗组和对照组。对苏木精伊红染色（HE）病理结果进行计算机灰度扫描半定量分析，用RNA酶保护实验的方法检测白细胞介素10/γ干扰素（IL-10/IFN-γ）mRNA的表达。结果 （1）气管内给人博莱霉素，使IL-10mRNA/IFN-γmRNA的比例由正常对照绵以IFN-γ为主的Th1优势逆转为以IL-10升高为主的Th2优势。（2）口服阿奇霉素治疗抑制IL-10，IFN-γmRNA在大鼠肺损伤模型中的表达；并于博莱霉素注入后第7天将模型中以IL-10升高为主的Th2优势逆转为IFN-γ为主的Th1优势；从病理上减轻了炎症细胞浸润和肺纤维化程度。结论 （1）致纤维化性肺泡炎早期，在肺泡上皮和基底膜损伤基础上的以IL-10升高为主的Th2优势反应及IFN-γ为主的Th1优势；从病理上减轻了炎症细胞浸润和肺纤维化程度，结论 （1）致纤维化性肺泡炎早期期，在肺泡上皮和基底膜损伤基础上的以IL-10升高为主的Th2优势反应及IFN-γ的相对缺乏，可能起到了促进纤维化形成的作用。（2）阿奇霉素可将博莱霉素致大鼠肺损伤模型中以IL-10升高为主的Th2优势逆转为IFN-γ为主的Th1优势，通过抗炎和免疫调节作用减轻了肺组织炎症损伤和肺纤维化程度。     

间质性肺疾病的发病机制

近年来,肺纤维化发病机制研究取得了许多非常重要的进展,尤其在蛋白水平上.本文基于目前国内外对肺纤维化的研究进展,对其发病机制作扼要综述.     

硒与GSH联合对氟致大鼠脂质过氧化作用的影响

目的　研究抗氧化剂硒及与不同剂量 GSH联合对氟所致脂质过氧化作用的影响。方法　采用动物实验。结果　饮含氟化钠 (15 0 mg/ L)水可使大鼠肝、肾及血清中 L PO含量显著增加 ;SOD活性、GSH- Px活性、GSH含量均显著下降 ;饮含氟水同时给亚硒酸钠 ,可使血清中 L PO含量显著下降 ;SOD活性、GSH- Px活性、GSH含量显著升高。说明硒对氟引起的脂质过氧化有拮抗作用。饮含氟水同时给 Se与不同剂量 GSH后 ,结果显示 :Se与低、中、高 3个剂量 GSH均可使血清中 L PO含量显著下降 ,全血中 SOD活性显著增强 ,呈剂量—效应关系 ,使肝、肾及全血中 GSH- Px活性不同程度增强 ,表明 Se与 GSH联合可有效拮抗氟所致的脂质过氧化作用 ,恢复机体抗氧化能力。结论　 1氟可引起大鼠肝、肾及全血中脂质过氧化物含量升高 ,抗氧化能力下降 ;2硒及与不同剂量 GSH联合具有不同程度拮抗氟诱导的脂质过氧化作用 ,恢复机体的抗氧化能力