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吡非尼酮对百草枯中毒致大鼠肺纤维化的影响。

Effect of pirfenidone on pulmonary fibrosis due to paraquat poisoning in rats.

机构信息

Pulmonary and Critical Care Research Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Clin Toxicol (Phila). 2012 Sep;50(8):754-8. doi: 10.3109/15563650.2012.718783.

Abstract

BACKGROUND

This study investigated the effectiveness of pirfenidone compared with antioxidants, in the prevention of pulmonary fibrosis and increasing the survival in acutely paraquat poisoned rats.

METHODS

Five groups of ten rats were included in this study. Three groups were poisoned with intraperitoneal injection of 15 mg/kg paraquat. Among these poisoned groups, one group was treated with vitamin C (500 mg/kg, intraperitoneal), vitamin E (200 mg/kg, intraperitoneal) and N-acetylcysteine (250 mg/kg, intravenous); two others were treated with either normal saline or pirfenidone (200 mg/kg, intravenous); two groups were not poisoned and received normal saline or pirfenidone (200 mg/kg, intravenous). All injections except paraquat were repeated in four consecutive days. On the 15th day of study a semi-quantitative determination of lung fibrosis was done using Ashcroft staging criteria on the lung sections.

RESULTS

Pirfenidone decreased paraquat induced lung fibrosis (p < 0.001) while antioxidants did not decrease the lung fibrosis (p = 0.413). Life expectancy decreased in paraquat + normal saline (11 days, 95% CI 7.94-14.05) and paraquat + antioxidant (11 days, 95% CI 7.77-14.23) groups. The increase in the survival of rats in paraquat/pirfenidone group was insignificant (13.4 days, 95% CI 11.13-15.67).

CONCLUSION

This study showed that pirfenidone is able to decrease pulmonary fibrosis following paraquat poisoning in a rat model.

摘要

背景

本研究旨在探讨吡非尼酮与抗氧化剂相比,在预防百草枯中毒性肺纤维化和提高急性百草枯中毒大鼠生存率方面的效果。

方法

本研究纳入了 50 只大鼠,分为 5 组,每组 10 只。其中 3 组大鼠通过腹腔注射 15mg/kg 百草枯进行中毒处理。在这些中毒组中,1 组接受维生素 C(500mg/kg,腹腔内注射)、维生素 E(200mg/kg,腹腔内注射)和 N-乙酰半胱氨酸(250mg/kg,静脉注射)治疗;另外 2 组分别接受生理盐水或吡非尼酮(200mg/kg,静脉注射)治疗;其余 2 组未进行中毒处理,接受生理盐水或吡非尼酮(200mg/kg,静脉注射)治疗。除百草枯外,所有注射均在连续 4 天内重复进行。在研究的第 15 天,使用 Ashcroft 分期标准对肺组织切片进行半定量纤维化测定。

结果

吡非尼酮可降低百草枯诱导的肺纤维化(p<0.001),而抗氧化剂则不能降低肺纤维化(p=0.413)。在百草枯+生理盐水(11 天,95%置信区间 7.94-14.05)和百草枯+抗氧化剂(11 天,95%置信区间 7.77-14.23)组中,预期寿命缩短。在百草枯/吡非尼酮组中,大鼠的生存率略有增加(13.4 天,95%置信区间 11.13-15.67)。

结论

本研究表明,吡非尼酮可降低百草枯中毒大鼠模型的肺纤维化程度。

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