Lorrot Mathie, Martin Sandra, Vasseur Monique
Institut National de la Santé et de la Recherche Médicale, Unité 510, Faculté de Pharmacie, Université de Paris XI, 92296 Châtenay-Malabry, France.
J Virol. 2003 Sep;77(17):9305-11. doi: 10.1128/jvi.77.17.9305-9311.2003.
Rotavirus is a major cause of infantile gastroenteritis worldwide. However, the mechanisms underlying fluid and electrolyte secretion associated with diarrhea remain largely unknown. We investigated the hypothesis that loss of Cl(-) into the luminal contents during rotavirus infection may be caused by a dysfunction in the chloride absorptive capacity across the intestinal brush-border membrane (BBM). The luminal Cl(-) concentrations in the entire small intestine of young rabbits infected with lapine rotavirus decreased at 1 and 2 days postinfection (dpi), indicating net Cl(-) absorption. At 7 dpi, luminal Cl(-) concentrations were slightly increased, indicating a moderate net Cl(-) secretion. By using a rapid filtration technique, (36)Cl uptake across BBM was quantified by modulating the alkali-metal ion, electrical, chloride, and/or proton gradients. Rotavirus infection caused an identical, 127% +/- 24% increase in all Cl(-) uptake activities (Cl(-)/H(+) symport, Cl(-) conductance, and Cl(-)/anion exchange) observed across the intestinal BBM. The rotavirus activating effects on the symporter started at 1 dpi and persisted up to 7 dpi. Kinetic analyses revealed that rotavirus selectively affected the capacity parameter characterizing the symporter. We report the novel observation that rotavirus infection stimulated the Cl(-) reabsorption process across the intestinal BBM. We propose that the massive Cl(-) reabsorption in villi could partly overwhelm chloride secretion in crypt cells, which possibly increases during rotavirus diarrhea, the resulting imbalance leading to a moderate net chloride secretion.
轮状病毒是全球婴幼儿肠胃炎的主要病因。然而，腹泻相关的液体和电解质分泌的潜在机制仍 largely 未知。我们研究了这样一个假说，即轮状病毒感染期间管腔内容物中 Cl⁻ 的流失可能是由于肠道刷状缘膜（BBM）上氯化物吸收能力的功能障碍所致。感染兔轮状病毒的幼兔整个小肠管腔中的 Cl⁻ 浓度在感染后 1 天和 2 天（dpi）下降，表明有净 Cl⁻ 吸收。在 7 dpi 时，管腔 Cl⁻ 浓度略有增加，表明有适度的净 Cl⁻ 分泌。通过使用快速过滤技术，通过调节碱金属离子、电、氯和/或质子梯度来量化跨 BBM 的 (³⁶)Cl 摄取。轮状病毒感染导致在肠道 BBM 上观察到的所有 Cl⁻ 摄取活动（Cl⁻/H⁺ 同向转运、Cl⁻ 电导和 Cl⁻/阴离子交换）均出现相同的、127%±24% 的增加。轮状病毒对同向转运体的激活作用在 1 dpi 开始并持续到 7 dpi。动力学分析表明，轮状病毒选择性地影响表征同向转运体的容量参数。我们报告了一项新的观察结果，即轮状病毒感染刺激了跨肠道 BBM 的 Cl⁻ 重吸收过程。我们提出，绒毛中大量的 Cl⁻ 重吸收可能部分压倒了隐窝细胞中的氯化物分泌，而在轮状病毒腹泻期间隐窝细胞中的氯化物分泌可能增加，由此产生的不平衡导致适度的净氯化物分泌。
