Grupo de Virologia, Unidade de Microbiologia Médica, Centro de Malária e outras Doenças Trópicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal.
J Virol. 2014 Mar;88(6):3161-9. doi: 10.1128/JVI.02927-13. Epub 2013 Dec 26.
The disease mechanisms associated with onset and secondary effects of rotavirus (RV) diarrhea remain to be determined and may not be identical. In this study, we investigated whether onset of RV diarrhea is associated with increased intestinal permeability and/or motility. To study the transit time, fluorescent fluorescein isothiocyanate (FITC)-dextran was given to RV-infected adult and infant mice. Intestinal motility was also studied with an opioid receptor agonist (loperamide) and a muscarinic receptor antagonist (atropine). To investigate whether RV increases permeability at the onset of diarrhea, fluorescent 4- and 10-kDa dextran doses were given to infected and noninfected mice, and fluorescence intensity was measured subsequently in serum. RV increased transit time in infant mice. Increased motility was detected at 24 h postinfection (h p.i.) and persisted up to 72 h p.i in pups. Both loperamide and atropine decreased intestinal motility and attenuated diarrhea. Analysis of passage of fluorescent dextran from the intestine into serum indicated unaffected intestinal permeability at the onset of diarrhea (24 to 48 h p.i.). We show that RV-induced diarrhea is associated with increased intestinal motility via an activation of the myenteric nerve plexus, which in turn stimulates muscarinic receptors on intestinal smooth muscles.
We show that RV-infected mice have increased intestinal motility at the onset of diarrhea, and that this is not associated with increased intestinal permeability. These new observations will contribute to a better understanding of the mechanisms involved in RV diarrhea.
轮状病毒（RV）腹泻的发病机制和继发效应仍有待确定，而且可能并不相同。在这项研究中，我们研究了 RV 腹泻的发病是否与肠通透性增加和/或运动性增加有关。为了研究转运时间，我们给 RV 感染的成年和婴儿小鼠给予荧光异硫氰酸荧光素（FITC）-葡聚糖。我们还使用阿片受体激动剂（洛哌丁胺）和毒蕈碱受体拮抗剂（阿托品）来研究肠道运动性。为了研究 RV 是否在腹泻发病时增加通透性，我们给感染和未感染的小鼠给予荧光 4-和 10kDa 葡聚糖剂量，随后在血清中测量荧光强度。RV 增加了婴儿小鼠的转运时间。在感染后 24 小时（h p.i.）检测到运动性增加，并在幼鼠中持续到 72 h p.i.。洛哌丁胺和阿托品均降低了肠道运动性并减轻了腹泻。从肠道进入血清的荧光葡聚糖的传递分析表明，腹泻发病时肠通透性没有受到影响（24 至 48 h p.i.）。我们表明，RV 诱导的腹泻与通过激活肌间神经丛引起的肠道运动性增加有关，而肌间神经丛反过来又刺激肠平滑肌上的毒蕈碱受体。
我们表明，RV 感染的小鼠在腹泻发病时肠道运动性增加，而这与肠通透性增加无关。这些新发现将有助于更好地理解 RV 腹泻相关的机制。
