臺灣博碩士論文加值系統

非類固醇止痛藥 Indomethacin 具有良好解熱、止痛、抗發炎的效果，是許多關節炎的病人常用的藥物，但在臨床上常因引起胃潰瘍的副作用，使病患在服用時須與制酸劑一起使用，效果卻不明顯。本研究目的是利用中藥治療胃腸疾病之平胃散與 Indomethacin 合併使用後，探討是否可以降低其副作用且不影響療效。利用Indomethacin 誘導胃黏膜細胞損傷及大鼠胃潰瘍，再合併使用平胃散，體外實驗結果顯示： 0.625~2.5mg / ml 的平胃散具有劑量依存性抑制 0.5 mM Indomethacin 誘導胃黏膜細胞毒性。體內實驗結果：餵服 200 mg / kg 之平胃散可減緩 40 mg/ kg Indomethacin 所誘導之大鼠胃潰瘍。再以 1% 鹿角菜膠誘發老鼠足掌腫脹中，評估平胃散與Indomethacin 合併之抗發炎作用，結果顯示：平胃散 200 mg / kg 未影響 Indomethacin 之抗發炎作用且可延長其作用時間。最後，檢測 Indomethacin 與平胃散合併後， Indomethacin 的
血中濃度的變化，結果顯示： 200 mg / kg 平胃散合併使用時，
Indomethacin 之血中濃度亦不會被影響。根據上述結果，平胃散可降低Indomethacin 誘導之胃潰瘍副作用，且不影響 Indomethacin 之原有抗發炎功效及血中濃度。此結果可做為中、西藥整合治療之參考。

Indomethacin is one of the commonly used non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of arthritis. However,gastric ulcer is a common side effect of this drug. The purpose of this study was to investigate the effect of combined administration of indomethacin with Ping-wei san (PWS), a commonly used traditional Chinese medicine for the treatment of gastrointestinal disease, on reducing the side effects of indomethacin without affecting its efficacy. Indomethacin (0.5 mM) was used to induce gastric mucosal cell injury and gastric ulcer. Co-administration of PWS (0.625 ~ 2.5 mg / ml) resulted in a dose-dependent inhibition of indomethacin-induced gastric mucosal cell toxicity. PWS (200 mg / kg) could also reduce the indomethacin (40 mg / kg)-induced gastric ulcer in in vivo experiment. PWS (200 mg / kg) also augmented the anti-inflammatory effect of indomethacin in 1% carrageen-induced foot swelling in rat. Finally, pharmacokinetic study revealed that PWS co-treatment did not influence plasma level of indomethacin. Based on the above results, co-treatment with PWS reduced the occurrence of indomethacin-induced gastric ulcers without affecting the anti-inflammatory effect and the plasma concentration of indomethacin This result demonstrated an useful integration therapy of western and Chinese medicine.

目錄……………………………………………………………………1
圖目錄…………………………………………………………………3
表目錄…………………………………………………………………5
縮寫表…………………………………………………………………6
中文摘要………………………………………………………………8
英文摘要………………………………………………………………9
緒論………………………………………………………………… 10
實驗材料與方法…………………………………………………… 23
1.實驗材料………………………………………………………… 27
2.實驗方法………………………………………………………… 27
2-1. 平胃散之製備………………………………………………… 27
2-2. 平胃散之指標成分分析……………………………………… 27
2-3. Indomethacin 誘導胃黏膜細胞毒性之體外試驗………… 29
2-4. Indomethacin 誘導大鼠胃潰瘍之體內試驗……………… 33
2-5. LPS 誘導RAW 264.7 細胞之體外抗發炎試驗……………… 34
2-6. Carrageenan 誘導大鼠足掌腫脹試驗……………………… 36
2-7. 血液中Indomethacin 濃度分析…………………………… 38
2-8. 統計方法……………………………………………………… 39
結果………………………………………………………………… 40
1. 平胃散之指標成分含量……………………………………… 40
1-1. Glycyrrhizin 及 Hesperidin 之檢量線………………… 40
1-2. Glycyrrhizin 及 Hesperidin 同日內與異日內結果…… 41
1-3. 平胃散之指紋圖譜…………………………………………… 41
2. 平胃散對Indomethacin 誘導之胃黏膜細胞損傷保護作用… 42
2-1. 初代大鼠胃黏膜細胞之分離及鑑定………………………… 42
2-2. 平胃散對胃黏膜細胞之毒性作用…………………………… 43
2-3. Indomethacin 對於胃黏膜細胞之毒性作用……………… 43
2-4. 平胃散與Indomethacin 誘導胃黏膜細胞損傷之保護作用…44
3. 平胃散對ndomethacin 誘導大鼠胃潰瘍之保護作用………… 46
3-1. Indomethacin 引發大鼠胃潰瘍之實驗建立……………… 46
3-2. 平胃散保護Indomethacin 誘導大鼠胃潰瘍試驗………… 46
3-3. 大鼠急性胃潰瘍之病理切片………………………………… 48
4. 平胃散與Indomethacin 單獨使用及合併使用對LPS 誘導RAW 264.7 巨噬細胞發炎之抑制作用………………………………… 49
5. 平胃散與Indomethacin 合併對Carrageenan 誘導大鼠足掌之抑制腫脹作用…………………………………………………………… 51
5-1. 大鼠足掌腫脹抑制作用……………………………………… 51
5-2. 足掌腫脹試驗之血清中PGE2 含量的測定………………… 52
6. 平胃散與Indomethacin 合併使用之血液中Indomethacin
濃度變化…………………………………………………………… 52
6-1. 血清中Indomethacin 萃取率……………………………… 52
6-2. 血清中Indomethacin 檢量線……………………………… 53
6-3. 血清中Indomethacin 含量分析…………………………… 53
討論………………………………………………………………… 55
參考文獻…………………………………………………………… 57

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