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己酮可可碱对盐酸氯丙嗪诱导的肺损伤中肿瘤坏死因子-α及肺组织病理学的影响。

Effects of pentoxifylline on TNF-alpha and lung histopathology in HCL-induced lung injury.

作者信息

Oliveira-Júnior Itamar Souza, Maganhin Carla Cristina, Carbonel Adriana Aparecida Ferraz, Monteiro Cristina Maria Rodrigues, Cavassani Sâmia Santos, Oliveira-Filho Ricardo Martins

机构信息

Surgery Center, Department of Surgery, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

出版信息

Clinics (Sao Paulo). 2008 Feb;63(1):77-84. doi: 10.1590/s1807-59322008000100014.

Abstract

OBJECTIVE

To evaluate the effects of pentoxifylline on hydrochloric acid-induced lung lesions in rats subjected to mechanical ventilation.

METHODS

Twenty male, adult Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: control-MV (mechanical ventilation, MV group); bilateral instillation of HCl (HCl group); bilateral instillation of HCl followed by pentoxifylline (50 mg/kg bw) infusion (HCl+PTX group) and pentoxifylline infusion followed by bilateral instillation of HCl (PTX+HCl group). At 20, 30, 90 and 180 min after treatments, the blood partial pressures of CO2 and O2 were measured. The animals were euthanized, and bronchoalveolar lavages were taken to determine the contents of total proteins, corticosterone [corrected] and TNF-alpha. Samples of lung tissue were used for histomorphometric studies and determining the wet-to-dry (W/D) lung weight ratio.

RESULTS

In the MV group, rats had alveolar septal congestion, and, in the HCl group, a remarkable recruitment of neutrophils and macrophages into the alveoli was noticed; these events were reduced in the animals with PTX+HCl. The partial pressure of oxygen increased in PTX+HCl animals (121+/-5 mmHg) as compared with the HCl (62+/-6 mmHg) and HCl+PTX (67+/-3 mmHg) groups within 30 minutes. TNF-alpha levels in bronchoalveolar lavage were significantly higher in the HCl group (458+/-50 pg/mL), reduced in the HCl+PTX group (329+/-45 pg/mL) and lowest in the PTX+HCl group (229+/-41 pg/mL). The levels of corticosterone [corrected] in bronchoalveolar lavage were significantly lower in the HCl (8+/-1.3 ng/mL) and HCl+PTX group (16+/-2 ng/mL) and were highest in the PTX+HCl (27+/-1.9 ng/mL).

CONCLUSION

Pretreatment with PTX improves oxygenation, reduces TNF-alpha concentration and increases the concentration of corticosterone [corrected] in bronchoalveolar lavage upon lung lesion induced by HCl.

摘要

目的

评估己酮可可碱对机械通气的大鼠盐酸诱导的肺损伤的影响。

方法

将20只成年雄性Wistar-EPM-1大鼠麻醉后随机分组(每组n = 5只动物)如下:对照组-机械通气组(MV组);双侧滴注盐酸组(HCl组);双侧滴注盐酸后静脉输注己酮可可碱(50 mg/kg体重)组(HCl + PTX组);静脉输注己酮可可碱后双侧滴注盐酸组(PTX + HCl组)。在处理后20、30、90和180分钟,测量血液中二氧化碳和氧气的分压。对动物实施安乐死,进行支气管肺泡灌洗以测定总蛋白、皮质酮[校正后]和肿瘤坏死因子-α的含量。取肺组织样本用于组织形态计量学研究并测定肺湿重与干重(W/D)比值。

结果

在MV组中,大鼠出现肺泡间隔充血,在HCl组中,观察到大量中性粒细胞和巨噬细胞募集到肺泡中;在PTX + HCl组动物中这些情况有所减轻。与HCl组(62±6 mmHg)和HCl + PTX组(67±3 mmHg)相比,PTX + HCl组动物在30分钟内氧分压升高(121±5 mmHg)。支气管肺泡灌洗中肿瘤坏死因子-α水平在HCl组显著更高(458±50 pg/mL),在HCl + PTX组降低(329±45 pg/mL),在PTX + HCl组最低(229±41 pg/mL)。支气管肺泡灌洗中皮质酮[校正后]水平在HCl组(8±1.3 ng/mL)和HCl + PTX组(16±2 ng/mL)显著更低,在PTX + HCl组最高(27±1.9 ng/mL)。

结论

PTX预处理可改善氧合,降低肿瘤坏死因子-α浓度,并在HCl诱导的肺损伤时增加支气管肺泡灌洗中皮质酮[校正后]的浓度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fbb/2664181/957f6ae7a9d6/cln63_1p0077f1.jpg

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