鋅化合物對照射小鼠之影響 有關體重、骨髓及腸黏膜細胞凋亡之研究

Effect of zinc compound in irradiated mice: specific on the changes of body weights, bone marrow and apoptosis in intestine mucosa

黃旼儀(Ming-Yii Huang)

指導教授 ： 吳信隆 ； 連熙隆

高雄醫學大學/藥學院/藥學研究所/碩士(2005年)

摘要

癌症病人接受腹部放射線治療時體重會減輕，骨髓機能會降低，並會有腸炎腹瀉等副作用，症狀嚴重時會影響治療療程。而鋅是一種人體必需的微量元素，它在人體內主要的生化生理功能為參與碳水化合物的代謝以及蛋白質合成與代謝，在體內亦可能扮演抗氧化的防禦機能。本研究的主要目的是在於含鋅化合物對於接受高能量光子放射線照射後小鼠之生長，以及對於骨髓及腸黏膜是否具有保護及促進修復的作用，能否減少放射線照射後的細胞傷害，藉以協助臨床上癌症治療的病患，減少放射線治療有關的副作用。
本實驗分別以：一、純水或氨基酸螯合鋅加上前列腺萃取物來餵食各組小鼠，以直線加速器之高能量光子射線施行小鼠之全身照射後，執行體重變化紀錄，定期解剖小鼠並取其大腿骨之骨髓以劉氏染色〈Liu stain〉觀察骨髓細胞的變化。二、葡萄酸鋅、氨基酸螯合鋅加上前列腺萃取物與純水分別來餵食各組小鼠，以直線加速器之高能量光子射線施行小鼠之腹部照射後，執行體重變化紀錄，定期解剖後將小鼠腸黏膜切片作蘇木素與伊紅染色〈Hematoxylin & Eosin stain〉並以TUNEL標記法〈Terminal deoxynucleotidyl transferase(TdT) - mediated dUTP nick-end labeling assay〉來識別凋亡細胞。
研究結果顯示，放射線照射劑量愈大則小鼠的體重愈輕、存活愈短。從骨髓及腸病理切片染色結果中，接受較高放射線照射劑量的小鼠其骨髓恢復情況差，而腸黏膜細胞的凋亡細胞數目較多。餵鋅組與無餵鋅組小鼠來比較，發現餵鋅化合物對於接受放射線照射後小鼠的成長有幫助。在照射6格雷與照射3格雷的小鼠均顯示餵含鋅化合物組小鼠平均體重比無餵鋅組高。有服用鋅化合物的小鼠比未服用鋅化合物的小鼠在接受放射線照射後的骨髓影響較少，腹部照射方面其腸黏膜細胞的凋亡細胞數目也較少。而餵食不同含鋅化合物結果顯示，餵氨基酸螯合鋅加上前列腺萃取物比餵葡萄酸鋅的小鼠腸黏膜細胞的凋亡細胞數目比較少。

關鍵字

高能放射線照射 ； 體重 ； 鋅化合物 ； 凋亡 ； 骨髓

並列摘要

The common side effects of cancer patients who received abdominal radiotherapy were body weight loss, bone marrow suppression, enteritis and diarrhea. The symptoms could affect the course of treatment, and in severe cases treatment might be suspended. Zinc is an essential trace element. It has various biochemical and physiological functions in human living systems including the metabolism of carbohydrate, the synthesis and metabolism of protein, and in additionally antioxidation in living cell.
This study is to evaluate the effects of zinc compound on mice body weight, bone marrow and intestine mucosa which was exposed to high energy photon beam irradiation; the potentiation of cell damage, as in reduction and repair after irradiation were of special interest. Clinically the zinc compound may ameliorate the side effects of radiotherapy in cancer patients. This study was divided into two experiments. The first experiment was included mice were administered pure water and zinc amino acid chelated bovine prostate extract respectively, and then irradiated with high energy photon beam to the whole body of mice. Subsequently, the body weight changes and histological change of bone marrow were examined. In the second experiment, mice were administered zinc gluconate, zinc amino acid chelated bovine prostate extract and pure water respectively, the mice were irradiated with high energy photon beam irradiation limited to the abdomen. The body weight changes and histological change of the intestinal mucosa were examined via the Hematoxylin & Eosin stain and TUNEL assay (Terminal deoxynucleotidyl transferase (TdT) - mediated dUTP nick-end labeling assay) to recognize the number of apoptotic cells.
This study revealed that the mice with higher radiation doses had lower the body weights and a poor survival rate. Histological change showed poorer recovery of bone marrow cells and in the large radiation dose group showed there was marked apoptosis in the intestinal mucosa. The comparison of body weights between non-administered vs. administered zinc mice showed higher mean body weight in the irradiated and administered zinc group. Zinc is beneficial to body weight in post-irradiation mice. Histological examination of the bone marrow and intestinal mucosa showed better recovery of bone marrow cells and less apoptosis in both groups of mice administered zinc. The results for the different zinc compound treatment groups revealed the intestinal mucosa of mice administered zinc amino acid chelated bovine prostate extract had fewer apoptotic cells than these administered zinc gluconate.

並列關鍵字

high energy photon beam irradiation ； zinc compound ； apoptosis ； body weight ； bone marrow

參考文獻

1. Erol FS, Topsakal C, Ozveren MF, et.al. Protective effects of melatonin and vitamin E in brain damage due to gamma radiation: an experimental study. Neurosurg Rev 2004;27(1):65-9.

2. Vijayalaxmi, Reiter RJ, Tan DX, et al. Melatonin as a radioprotective agent: a review. Int J Radiat Oncol Biol Phys 2004;59(3):639-53.

3. Sener G, Atasoy BM, Ersoy Y, et al. Melatonin protects against ionizing radiation-induced oxidative damage in corpus cavernosum and urinary bladder in rats. J Pineal Res 2004;37(4):241-6.

4. Ferreira PR, Fleck JF, Diehl A, et al. Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: a double-blind randomized trial. Head Neck 2004;26(4):313-21.

5. Amifostine reduces radiation therapy-induced dry mouth in head and neck cancer patients. Oncology (Huntingt) 2004;18(10):1314-6.