目的：唾液腺具極高之輻射敏感度，鼻咽癌病人接受放射治療後，唾液腺遭破壞，造成病人之唾液分泌大幅降低。如何在放射治療過程中保護唾液腺，方法之一是使用能減低唾液輻射傷害的保護劑如pentoxifylline、amifostine等。此外有許多藥物可能具唾液保護的效果如維它命C、腎上腺素激性藥物（adrenergic agonist）及膽素刺激性（cholinergic）藥物。本研究使用解剖、生理與人類近似之迷你豬，目的為1. 建立迷你豬唾液腺研究的動物模式。2. 測試篩選能有效刺激迷你豬唾液分泌的最適當方法。3. 得到初步迷你豬腮腺放射反應資料。材料及方法：採用台大畜產所體重約10-15公斤之李宋系迷你豬。經麻醉、插管後，再行唾液收集、藥物注射、放射線照射或手術。唾液刺激採藥物與電刺激方式找出最佳刺激方式。膽素刺激性藥物Carbachol及a-腎上腺素激性藥物Cyclocytidine與Norepinephrine均在測試之列。放射腺照射以6MV直線加速器為之。整個實驗架構如下：一、動物模式建立。建立小豬麻醉方法，選擇唾液刺激方法（神經刺激或藥物刺激），決定唾液收集方法。二、腮腺照射前後之唾液分泌功能。收集未照射前兩側腮腺唾液，右側腮腺照射1000 cGy x 2、300 cGy x 15、與400 cGy x 12後於一週、一個月與四個月時以藥物刺激後，收集唾液比較照射與未照射側腮腺分泌量之變化。結果：經測試Carbachol 0.2 mg/kg最為適當，可刺激唾液大量分泌，且可重複驗證，再現性極佳。但使用carbachol仍可能導致心跳停止，常須進行心臟按摩搶救小豬。此情況於靜注1cc atropine後心跳均可立即恢復。電刺激方式則無法刺激唾液分泌。在唾液收集方面，發現以乾燥2 x 2 cm紗布塞於腮腺唾液管乳頭處之收集法，最為可靠及穩定。經照射1000 cGy x 2後一週及一個月唾液分泌為2.93 ml/min，未照射腮腺分泌量為3.0ml/min。照射4500 cGy與4800 cGy一週及一個月後，未照射之左腮腺及照射之右腮腺唾液分泌量亦無差別。照射4500 cGy與4800 cGy四個月後，未照射與照射腮腺分泌量分別為2.56/1.08與6.83/1.99 ml/min，照射過之腮腺表現明顯分泌量的減少。此時照射後腮腺明顯萎縮，兩隻接受4500 cGy與4800 cGy小豬之未照射與照射側腮腺之重量分別為127.9/26.9克、125.7/22.1克。結論：以迷你豬為材料，取其解剖與生理較大鼠更近似人類，唾液量夠大等優點。惟與大鼠相較，迷你豬成本高出許多，以致實驗規模無法與使用老鼠時相比。本研究建立之動物模式，能可靠重複刺激迷你豬之腮腺唾液分泌。Carbachol為一有效之唾液刺激藥物，但有心臟停止跳動的缺點。相反的Adrenergic類藥物norepinephrine則不用擔心心跳停止，但唾液刺激效率不好，但若提高norepinephrine的劑量能否增強其唾液刺激效果，仍有待進一步研究。唾液腺在人類為早期即出現之反應，但又有晚期反應組織的特色。本研究則發現迷你豬腮腺未出現早期反應，此點發現與人類唾液腺經照射360-720 cGy後即明顯出現唾液分泌降低有顯著差異，其造成之原因有待進一步的研究。本研究之結果將可作為後續動物實驗之基礎，最終希望能用於治療或預防鼻咽癌病人唾液腺傷害之副作用。

Purpose : Salivary glands are extremely radiosensitive organs, and are inevitably destroyed during the course of radiotherapy in NPC patients. One of the possible preventive approaches for radiation-induced salivary gland damage is the use of parotid-protecting drugs including pentoxifylline and amifostine. A few other drugs including adrenergic and cholinergic agonists have been tested for their salivary protection effect. The goals for this study are: 1. To establish an animal model using miniature pigs for study of radiation protection of parotid gland. 2. To find out an effective agent for saliva stimulation. 3. To conduct a preliminary study of radiation effect on parotid gland using this animal model. Methods & Materials : Lee-Song species of miniature pigs 3-4 months old weighing about 10-15 kg were used. They were anaesthetized and intubated followed by salivary collection, drug stimulation, irradiation or surgery. Drugs including cholinergic stimulant carbachol, adrenergic agonists cyclocytidine and norepinephrine were tested for their efficacy in saliva-stimulation. Electric stimulation was also tested. The entire study structure was as follows: 1. For animal model establishment: anaesthesia procedure, optimization of salivary gland stimulation (physical and chemical approach), optimization of saliva collection. 2. For dose-response study of parotid glands: parotid secretion of unirradiated pigs, right parotid irradiation with 1000 cGy x 2, 300 cGy x 15, and 400 cGy x 12 and assayed for parotid function 1 week, 1 month and 4 months after completion of irradiation. Results : Carbachol 0.2 mg/kg was most efficient for stimulating salivary secretion in a reproducible way. Yet this drug induced cardiac arrest and cardiac massage was needed sometimes. However, this can be reversed immediately after iv bolus of 1 ml of atropine. For saliva collection, using dry, 2 x 2 inch gauze to suck the secretion proves to be accurate and feasible. One week and 1 month after 1000 cGy x 2 the control versus irradiated parotid secretion is 3.0/2.93 ml/min. The difference between control and irradiated glands was also insignificant 1 week and 1 month after 4500 cGy and 4800 cGy. However, at 4 months, a marked difference in parotid secretion occurred with the control/irradiated of 2.56/1.08 and 6.83/1.99 ml/min, respectively. At 4 months, the irradiated gland was also markedly atrophic and the weight for control/irradiated parotids in 2 experiments was 127.9/26.9 gm after 4500 cGy and and 125.7/22.1 gm after 4800 cGy, respectively. Conclusion : Advantages using minipig as the model include the higher similarity with humans than rodents in terms of physiology and anatomy and the much larger salivary secretion volume. The only disadvantage is the higher cost that limits the sample size of the experiment. The animal model we have established is feasible for salivary stimulation and saliva collection that can be reproduced consistently. Carbachol proves to be very efficient for saliva stimulation and cardiac arrest is the only shortcoming. On the contrary, norepinephrine is less efficient for saliva stimulation but is free of the side effect of cardiac arrest. Salivary gland damage appears acutely in humans and persists for many years after completion of radiotherapy. In contrast to humans, minipig parotid gland did not show an evaluable early effect up to 1 month after radiotherapy. The nature of this discrepancy is interesting and requires further exploration. The result of this study may be used for future experiments aiming at prevention of radiation damage to the parotid glands.