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地塞米松与 COVID-19:一项与大型试验初步结果相符的实验研究。

Dexamethasone vs COVID-19: An experimental study in line with the preliminary findings of a large trial.

机构信息

Student Research Committee, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Int J Clin Pract. 2021 Jun;75(6):e13943. doi: 10.1111/ijcp.13943. Epub 2020 Dec 30.

Abstract

BACKGROUND

The preliminary report of the RECOVERY large randomised controlled trial indicated a promising survival effect for dexamethasone therapy of coronavirus disease 2019 (COVID-19). This study aimed to investigate the anti-hypoxic activities of dexamethasone to understand a possible mechanism of its action in hypoxia-induced lethality through experimental models of hypoxia.

METHODS

In this investigation, 84 Male BALB/c mice were randomly divided into groups of seven (12 groups). Treatment groups received 10 days of dexamethasone intraperitoneal injection at both human dose (0.1 mg/kg) and the animal does (1 mg/kg). Control negative and positive groups were treated with 10 ml/kg of normal saline and 30 mg/kg of propranolol, respectively. Three experimental models of hypoxia, asphyctic, circulatory, and hemic were applied in this study.

RESULTS

The findings showed that dexamethasone significantly prolonged the latency for death in the asphyctic model concerning the control group in both humans (P < .0001) and animal dose (P < .0001). The results were also highly significant for both doses in the hemic model (P < .001). In the circulatory model, although a small increase was observed in death prolongation, results were not statistically significant for both doses in this model (P > .05).

CONCLUSIONS

This experimental in vivo investigation demonstrated an excellent protective effect for 10 days of dexamethasone treatment against hypoxia, especially in asphyctic and hemic models. In addition to promising dexamethasone outcomes, using propranolol as the positive control illustrated a very substantial anti-hypoxic effect even much better than dexamethasone in all models. It seems that propranolol would be a safe, potential, and prudent choice to invest in treating COVID-19 patients.

摘要

背景

RECOVERY 大型随机对照试验的初步报告表明,地塞米松治疗 2019 年冠状病毒病(COVID-19)有可喜的生存效果。本研究旨在通过缺氧诱导致死的实验模型,研究地塞米松的抗缺氧活性,以了解其作用的可能机制。

方法

在这项研究中,84 只雄性 BALB/c 小鼠被随机分为 7 组(共 12 组)。治疗组接受 10 天的地塞米松腹腔注射,剂量分别为人用剂量(约 0.1mg/kg)和动物剂量(约 1mg/kg)。阴性对照和阳性对照组分别给予 10ml/kg 的生理盐水和 30mg/kg 的普萘洛尔。本研究应用了三种缺氧实验模型,即窒息、循环和血液模型。

结果

结果显示,与对照组相比,地塞米松在窒息模型中显著延长了人类(P <.0001)和动物剂量(P <.0001)组的死亡潜伏期。对于血液模型,两种剂量的结果均高度显著(P <.001)。在循环模型中,尽管观察到死亡延长略有增加,但在该模型中,两种剂量的结果均无统计学意义(P >.05)。

结论

这项体内实验研究表明,地塞米松治疗 10 天对缺氧具有极好的保护作用,尤其是在窒息和血液模型中。除了地塞米松有希望的结果外,使用普萘洛尔作为阳性对照,即使在所有模型中都比地塞米松更好,也表明了其具有很强的抗缺氧作用。普萘洛尔似乎是治疗 COVID-19 患者的一种安全、有潜力和谨慎的选择。

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