阿奇霉素脂质体对博来霉素致大鼠肺纤维化的影响

目的研究阿奇霉素脂质体对博来霉素诱导大鼠肺纤维化的保护作用。方法 SD大鼠72只,随机分为空白对照组(n=6)、模型组(n=18)、溶液组(n=24)和脂质体组(n=24),后3组一次性向大鼠气管内注入博来霉素5 mg.kg-1制成肺间质纤维化模型,分别每日尾静脉注射给予生理盐水、阿奇霉素溶液(2.50 g.L-1)和阿奇霉素脂质体(2.61 g.L-1),连续28 d,各组分别于d 7、d 14、d 28和停药后d 28(d 56)处死。各组动物处死后测量肺重系数,测定肺组织匀浆内丙二醛(MDA)、羟脯氨酸(HP)含量,提取肺组织进行HE、Masson染色并进行病理半定量分析。结果博来霉素诱导大鼠肺重系数增加,MDA和HP含量增高、肺泡炎和肺纤维化显著,与空白对照组相比有非常显著差异(P<0.01)。d 7、d 14、d 28溶液组和脂质体组与同时点模型组相比肺重系数、MDA和HP含量均显著降低(P<0.05),脂质体组肺泡炎程度于不同时点均减轻(P<0.05)。脂质体组d 56与d 28相比无明显反弹(P>0.05),而溶液组出现反弹(P<0.05)。结论阿奇霉素脂质体能够有效地治疗病变过程中的肺泡炎,对纤维化有明显的防治作用,停药后能持续有效地发挥作用。     

柴胡皂甙d干预肺纤维化VEGF/PEDF表达的实验研究

摘要 目的 观察柴胡皂甙d（saikosaponin-d SSd）对博来霉素（BLM）致肺纤维化小鼠肺组织血管内皮生长因子（VEGF）/色素上皮衍生因子（PEDF）在不同时间表达变化的调节作用,并探讨其与抗肺纤维化作用的关系。 方法 将80只小鼠随机分为4组,正常对照组,模型组,SSd大、小剂量治疗组。治疗组分别每天腹腔注射不同剂量SSd, MASSON染色观察纤维化程度,样本碱水解法检测肺组织中羟脯氨酸（HYP）含量,免疫荧光观察PEDF、VEGF蛋白在肺内表达的规律,RT-PCR观察各时间点PEDF、VEGF mRNA表达的强度。 结果 MASSON染色示模型组、治疗组均纤维化逐渐进展的动态变化;HYP含量随时间逐渐增加;造模组VEGF表达从第三天开始升高,第7天达高峰,之后逐渐下降,28天到最低,PEDF表达总体呈现逐渐增高趋势;治疗组VEGF表达总体比单纯造模组降低,并呈剂量依赖关系;PEDF表达比造模组升高,呈剂量依赖关系;结论 SSd能够抑制肺纤维化进展,机制可能与下调VEGF的表达,上调PEDF的表达有关。     

清金补肺汤对博莱霉素致大鼠肺纤维化干预作用的研究

目的探讨清金补肺汤对实验性大鼠肺纤维化的保护作用及其相关机制。方法将45只清洁级Wistar雄性大鼠随机分为盐水对照组15只、BLM模型组15只和治疗组15只。模型组和治疗组采用一次性气管内注入BLM诱导大鼠肺纤维化模型,盐水对照组在相同条件下给予等量的生理盐水气管内滴注。治疗组造模后第2天起给予清金补肺汤2 mL灌胃,模型组和盐水对照组给予等量的蒸馏水灌胃。各组分别于造模后第7天、第14天和第28天随机处死5只大鼠,留取血清及肺组织。用酶联免疫吸附测定法检测血清中TNF-α的含量;应用HE染色和Masson染色观察肺泡炎和肺纤维化的动态变化。结果病理切片可见模型组造模成功。模型组大鼠血清中的TNF-α含量较盐水对照组各时间点明显升高(P均<0.01);与模型组比较,治疗组各时间点血清中TNF-α含量均明显降低(P均<0.01)。结论清金补肺汤可降低博莱霉素所致肺纤维化大鼠血清中TNF-α的含量;早期应用清金补肺汤干预治疗博莱霉素致肺纤维化大鼠,可减缓其肺纤维化进程。     

桔梗皂苷-D对大鼠肺纤维化的干预作用及部分机制研究

目的:研究桔梗皂苷-D(PD)对大鼠肺纤维化的干预作用。方法:50只Wistar大鼠随机分为假手术对照组、模型组、PD 25 mg/kg组、PD 50 mg/kg组、甲强龙组。大鼠一次性气管内滴注盐酸博莱霉素诱导肺纤维化模型。观察各组大鼠的生存状况;检测大鼠血清中I型胶原(C-I)、III前胶原肽(PIIIP)、透明质酸(HA)的含量并进行比较;检测大鼠肺组织TGF-βmRNA的表达情况。结果:PD组大鼠的生存率较模型组高,PD能有效降低大鼠血清中C-I、PIIIP、HA的含量(P0.05),并能下调大鼠肺组织TGF-βmRNA表达(P0.05)。结论:PD可以改善盐酸博莱霉素诱导的肺纤维化大鼠的一般情况,并通过抑制大鼠肺组织TGF-βmRNA表达,以达到抗纤维化的作用。     

Mechanism of Reduction of Bleomycin-Cu(II) by CO−2 and Oxidation of Bleomycin—Cu(I) by H2O2 in the Absence and Presence of DNA

Summary

The reduction reaction of bleomycin—Cu(II) by CO^?₂ has been studied by γ and pulse radiolysis at pH7. The CO^?₂ radical reduces bleomycin—Cu(II) at a rate of (6·7 ± 0·7) × 10⁸ dm³ mol^?1 s^?1. In the presence of calf thymus DNA the rate of the reduction decreased as the concentration of DNA increased, indicating that the reduction reaction proceeds through free bleomycin—Cu(II). The stoichiometry and the kinetics of the oxidation of bleomycin—Cu(I) by H₂O₂ in the presence and absence of DNA have been studied. Our observations suggest that the OH^· radical is not produced during this reaction and the degradation of the drug occurs in the absence and presence of DNA. We assume that bleomycin—Cu(II) in the presence of a reducing agent and molecular oxygen or H₂O₂ does not cleave DNA since the oxidizing species, which are formed during the oxidation reaction by H₂O₂, attack the drug even in the presence of DNA.     

Sensitivities of bleomycin-resistant variant cells enhanced by 40°C hyperthermia in vitro

Cultured mammalian cells of higher (mouse L) and lower (Chinese hamster V-79) sensitivities to bleomycin (BLM) were repeatedly treated with BLM (0.1 mg/ml), through which BLM-resistant variant strains were induced. Sensitivities of these variant strains to BLM were enhanced by simultaneous treatment with 40°C hyperthermia.     

Hydroxysafflor Yellow A Attenuates Bleomycin‐induced Pulmonary Fibrosis in Mice

Hydroxysafflor yellow A (HSYA) is an active component of Carthamus tinctorius L., and we want to investigate whether HSYA attenuates pulmonary fibrosis induced by bleomycin (BLM) in mice. The mice received a BLM via oropharyngeal aspiration, and HSYA was intraperitoneally injected. Arterial blood gas analysis was performed. Morphological changes and hydroxyproline content were measured. mRNA expression of transforming growth factor‐β1 (TGF‐β1), connective tissue growth factor, α‐smooth muscle actin (α‐SMA), and collagen I was measured by real‐time polymerase chain reaction. α‐SMA‐positive cells in lung tissues were detected by immunohistochemical staining. A549 cell was cultured, and morphological changes were observed after TGF‐β1 and HSYA treatment. mRNA expression was detected by real‐time polymerase chain reaction. Phosphorylation of Smad3 was evaluated by western blotting. HSYA decreased the lung consolidation area and collagen deposition in mice with pulmonary fibrosis. The blood gas changes due to BLM were attenuated by HSYA. HSYA also alleviated the BLM‐induced increase of TGF‐β1, connective tissue growth factor, α‐SMA, and collagen I mRNA levels. HSYA treatment inhibited the increase of α‐SMA expression, Smad3 phosphorylation, the morphological changes in lung tissue. HSYA inhibits Smad3 phosphorylation and elevated expression of collagen I mRNA in epithelial–mesenchymal transition induced by TGF‐β1. Copyright © 2016 John Wiley & Sons, Ltd.     

局部注射平阳霉素和确炎舒松A治疗小儿皮肤血管瘤的比较研究

目的 :　探讨和比较平阳霉素和确炎舒松A治疗小儿皮肤血管瘤的疗效。方法 :　 2 80例皮肤血管瘤患儿随机分为平阳霉素治疗组 (10 4例 )和确炎舒松A治疗组 (176例 ) ,平阳霉素组采用平阳霉素瘤体内注射 ,浓度为 2～ 3.2mg ml ;确炎舒松A组采用确炎舒松A瘤体内注射 ,浓度为 8mg ml。每 2周重复注射一次 ,总疗程 3～ 10次。结果 :　平阳霉素组 10 4例患儿中 ,治愈 89例 (治愈率 85 .6 % )和有效 15例 (14 .4 % ) ,确炎舒松A组 176例血管瘤患儿中 ,治愈 86例 (4 8.9% )和有效 75例 (4 2 .6 % )。两组比较差异有统计学意义 (P <0 .0 0 1)。结论 :　平阳霉素瘤体内注射治疗小儿皮肤血管瘤安全有效 ,其疗效优于确炎舒松A。