- 學位論文
咖啡因作用於外淚腺purinergic receptors促進淚液短期分泌之動態機制變化分析
Caffeine Promotes Short-Term Tear Secretion in Extraorbital Lacrimal Glands through Purinergic Receptors
摘要
咖啡因可能有助於緩解乾眼症是一項重要的課題，最近一項研究發現攝取咖啡因者罹患乾眼症的盛行率是13%，然而無攝取者的盛行率則是16.6%，另外近期有Arita et al. (2012) 與Osei et al. (2014) 兩篇小型臨床試驗的論文指出攝食咖啡因會增加淚液分泌量，但都缺少咖啡因促使淚液短期分泌的作用機制探討。因此本研究以小鼠in vivo與小鼠外淚腺ex vivo實驗分析咖啡因對淚液分泌的影響，並探討咖啡因作用於外淚腺P1和P2 purinergic receptors促進淚液短期分泌之路徑及其動態機制變化。In vivo實驗結果發現：一、ICR母鼠的外淚腺在10週齡時已足夠成熟，可對咖啡因的影響產生反應；二、20 mg/kg與40 mg/kg的咖啡因劑量在管餵後45與60分鐘時淚液量皆有顯著的增加，以40 mg/kg咖啡因劑量管餵45分鐘後的淚液分泌最多；三、在咖啡因的影響下，外淚腺中P1 receptor與P2 receptor皆有正向調控 (upregulation) 的現象。Ex vivo實驗結果發現在咖啡因的短期影響下，咖啡因主要是藉由淚腺中的P1 receptor促進淚液分泌，在P1和P2 receptors雙重抑制狀況下，交感與副交感神經末梢對於較長時間咖啡因的影響產生負回饋的效果，進而抑制淚液的分泌。本研究提供以咖啡因促進淚液分泌的基礎研究結果，將在未來幫助研發緩解乾眼症的新型藥物。
並列摘要
The potential of caffeine in alleviating dry eye syndrome has emerged as a notable topic in recent years. Recent research showed that the prevalence of dry eye syndrome among caffeine consumers is 13%, compared to 16.6% in non-caffeine consumers. Another two small-scale clinical trials by Arita et al. (2012) and Osei et al. (2014) indicated that caffeine intake increased tear secretion, yet the short-term mechanism behind this effect was not explained. This study investigated the effects of caffeine on tear secretion with in vivo experiments on mice and ex vivo experiments on mouse extraorbital lacrimal glands. The caffeine effects on pathways through of P1 and P2 purinergic receptors in the lacrimal glands and the dynamic mechanism were examined. The in vivo results revealed: 1. Extraorbital lacrimal glands of ICR female mice are sufficiently mature by 10 weeks of age to respond to caffeine. 2. Significant tear secretion increase was observed at 45 and 60 minutes after oral caffeine administration at 20 mg/kg and 40 mg/kg, with the highest secretion found at 45 minutes after 40 mg/kg caffeine administration. 3. Both lacrimal gland P1 and P2 receptors were upregulated after receiving caffeine. The ex vivo experiments demonstrated that caffeine primarily promotes tear secretion through the P1 receptor in the extraorbital lacrimal gland. Under dual inhibition of P1 and P2 receptors, a negative feedback effect from sympathetic and parasympathetic nerve endings was observed and tear secretion was inhibited. This study has provided the essential data on caffeine-induced tear secretion and contributed to lay up the foundation in developing novel pharmaceutics for dry eye syndrome.