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次氯酸和抗坏血酸对体外马结肠黏膜的电导、通透性及结构的影响

Effects of hypochlorous acid and ascorbic acid on conductance, permeability, and structure of equine colonic mucosa in vitro.

作者信息

Inoue O J, Freeman D E, Wallig M

机构信息

Department of Veterinary Clinical Medicine, University of Illinois, College of Veterinary Medicine, Urbana 61801, USA.

出版信息

Am J Vet Res. 1998 Jan;59(1):82-7.

PMID:9442250
Abstract

OBJECTIVES

To study effects of hypochlorous acid (HOCl) on equine colonic mucosa in vitro, and determine whether addition of ascorbic acid protects against the effects.

ANIMALS

6 healthy horses and ponies.

PROCEDURE

Short-circuit current was measured in mucosa mounted in Ussing chambers. Incubation conditions were: control (no additions); 5 mM HOCl; 1 mM HOCl; same and 5 mM ascorbic acid; 3 mM HOCl; 3 mM HOCl and 5 mM ascorbic acid; 7 mM HOCl; and 7 mM HOCl plus 5 mM ascorbic acid. Permeability was measured with [3H]mannitol and, at the conclusion of each experiment, tissues were examined microscopically to assess the effects of HOCl and ascorbic acid, alone or in combination.

RESULTS

Short-circuit current and conductance increased transiently in response to 1 mM HOCl. Tissues had mild surface epithelial damage, as evident by swelling and separation of isolated cells. These changes were abolished when tissues were coincubated with 5 mM ascorbic acid and 1 mM HOCl. At 3 and 7 mM concentrations, HOCl caused marked increase in tissue conductance, short-circuit current, and permeability to mannitol; these changes were associated with histologic damage. Again, coincubation with 5 mM ascorbic acid protected against these changes. Additional studies indicated that the effects of HOCl and the protective effects of ascorbic acid were not mediated through changes in pH.

CONCLUSIONS

HOCl in low concentrations is capable or increasing the short-circuit current in equine colon, possibly by increasing secretions; however, higher concentrations can cause tissue damage. The addition of 5 mM ascorbic acid blocks these changes.

CLINICAL RELEVANCE

The concentration of HOCl produced by activated neutrophils could damage equine colonic mucosa and potentially contribute to or cause reperfusion injury. The ability of ascorbic acid to ameliorate this injury in an in vitro setting offers a potential method for pharmacologic evaluation of this injury and for treatment.

摘要

目的

研究次氯酸(HOCl)对马结肠黏膜的体外作用,并确定添加抗坏血酸是否能预防这些作用。

动物

6匹健康马和小马驹。

方法

在安装于尤斯灌流室的黏膜中测量短路电流。孵育条件为:对照(不添加);5 mM HOCl;1 mM HOCl;1 mM HOCl与5 mM抗坏血酸;3 mM HOCl;3 mM HOCl与5 mM抗坏血酸;7 mM HOCl;以及7 mM HOCl加5 mM抗坏血酸。用[3H]甘露醇测量通透性,并且在每个实验结束时,对组织进行显微镜检查以评估HOCl和抗坏血酸单独或联合使用的作用。

结果

响应1 mM HOCl,短路电流和电导短暂增加。组织有轻度表面上皮损伤,表现为分离细胞肿胀和脱离。当组织与5 mM抗坏血酸和1 mM HOCl共同孵育时,这些变化消失。在3 mM和7 mM浓度下,HOCl导致组织电导、短路电流和对甘露醇的通透性显著增加;这些变化与组织学损伤相关。同样,与5 mM抗坏血酸共同孵育可预防这些变化。进一步研究表明,HOCl的作用和抗坏血酸的保护作用不是通过pH变化介导的。

结论

低浓度的HOCl能够增加马结肠的短路电流,可能是通过增加分泌实现;然而,较高浓度会导致组织损伤。添加5 mM抗坏血酸可阻止这些变化。

临床意义

活化的中性粒细胞产生的HOCl浓度可能会损伤马结肠黏膜,并可能促成或导致再灌注损伤。抗坏血酸在体外环境中改善这种损伤的能力为评估这种损伤和进行治疗提供了一种潜在的药理学方法。

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