臺灣博碩士論文加值系統

臨床上，化學治療藥物順氯氨鉑(cisplatin, CDDP)常用於治療固體癌，其引起的腎毒性，常是限制臨床使用的主要因素。本研究利用低劑量CDDP連續投予小鼠，引發腎炎模型，以綠茶及(+)-catechin和sodium salicylate作為預防藥物，評估在此腎炎之預防效果。
實驗以6週齡雌鼠(BALB/c mice)藉由事先投予綠茶濃縮劑(GT 75, 150, 300 mg/kg/d)及其純成分(+)-catechin（CAT 25, 50, 100 mg/kg/d）、化學藥品sodium salicylate 100 mg/kg/d（S）、併用CAT 50mg + S（S + C）來評估藥物對CDDP引起腎毒性的預防效果。實驗以N-acetyl--D-glucosaminidase (NAG)、urinary creatinine (Ucr.)與BUN評估腎功能；腎組織以PAS染色觀察病理組織及免疫螢光染色辨別其損傷部位之特異性抗原。
實驗結果顯示，GT 150 mg/kg/d、(+)-catechin 50 mg/kg/d及S + C皆可改善腎功能，組織學上腎小管受損的情形相較於對照組也較輕微。綜合實驗結果顯示，S + C對於預防CDDP所引起的腎毒性效果最好。

Cisplatin(CDDP) is one of the most commonly used antineoplastic agent for the treatment of solid tumor. The CDDP induced nephrotoxicity is dose-related and cumulative. It is the major dose-limiting toxicity of cisplatin. We used an established CDDP induced nephrotoxicity in inbred mice model to evaluate the effect of green tea extract, (+)-catechin and sodium salicylate.
Before administration of CDDP(i.p. 5mg/kg/d on day 1 to day 5), BALB/c mice（6 week, female）were administered orally with green tea extract(GT 75, 150, 300 mg/kg/d), (+)-catechin(CAT 25, 50, 100 mg/kg/d) , sodium salicylate 100 mg/kg/d(S) and combination of CAT 50 mg/kg/d and S(S + C) once daily for 10 days(on day -5 to day 5).
Urinary N-acetyl-β-D-glucosaminidase(NAG), urinary creatinine (Ucr.)and BUN were determined. Renal tissues were served to histological examination (PAS stain and immunofluorescence staining). The antibodies including TNF-, p21, cyclin D1 was chosen to recognize the specific antigens, which deposited in injury sites.
The result showed that GT 150 mg/kg/d、(+)-catechin 50 mg/kg/d and S + C can ameliorate renal damage. According to the study, the effect of S + C was superior to the other groups.

圖目錄 VI
表目錄 VIII
縮寫表…………………………………………………….……………………i
中 文 摘 要…………………………………………………………………..ii
ABSTRACT……………………………………………………………….....iii
第一章 緒言 1
第二章 文獻回顧 4
第一節 順氯氨鉑(Cisplatin)的作用機轉及臨床使用 4
第二節 Cisplatin引起腎毒性的臨床表徵與機轉 8
第三節 細胞週期(Cell cycle)的調控 17
第四節 綠茶 27
第五節 (+)-catechin的藥效研究 31
第六節 水楊酸鈉Sodium salicylate…………………....………………….33
第三章 研究目的 36
第四章 材料與方法 37
第一節 綠茶濃縮劑在CDDP引起腎炎模型的藥效評估 37
1.1實驗動物 37
1.2實驗藥物 37
1.3綠茶濃縮劑在此腎炎模型之實驗設計 37
1.4尿液收集 38
1.5動物犧牲法、血液及組織切片製作 38
1.6 尿中NAG、creatinine的含量測定 39
1.7血清中BUN值的含量測定 39
1.8 Periodoic Acid Schiff’s (PAS) stain組織染色 40
1.9組織損傷程度的量化 40
1.10免疫螢光染色 (Immunofluorescence) 41
1.11統計方法 41
第二節 (+)-catechin在CDDP引起腎炎模型的藥效評估 44
2.1實驗動物 44
2.2實驗藥物 44
2.3各種預防藥物在此腎炎模型之實驗設計 44
2.4 尿液收集…………………………………………………………….44
2.5 動物犧牲法、血液及組織切片製作……………………………….44
2.6 尿中NAG、creatinine的含量測定………………………………….44
2.7 血清中BUN值的含量測定………………………………………...44
2.8 Periodoic Acid Schiff’s(PAS) stain組織染色…………………….....44
2.9 組織損傷程度的量化……………………………………………….45
2.10 免疫螢光染色………………………..………………….…………45
2.11 統計方法…………………………………………………………...45
第三節 各種預防藥物在CDDP引起腎炎模型的藥效評估 47
3.1實驗動物 47
3.2實驗藥物 47
3.3各種預防藥物在此腎炎模型之實驗設計 47
3.4尿液收集 47
3.5動物犧牲法、血液及組織切片製作 47
3.6 尿中NAG、creatinine的含量測定 48
3.7血清中BUN值的含量測定 48
3.8 Periodoic Acid Schiff’s(PAS) stain組織染色 48
3.9組織損傷程度的量化 48
3.10免疫螢光染色 48
3.11統計方法 48
第五章 結果 50
第一節 綠茶濃縮劑在CDDP引起腎炎模型的藥效評估 50
1.1 尿中NAG、creatinine的含量分析 50
1.2 血清中BUN分析 51
1.3 組織病理PAS染色 51
1.4組織損傷量化分析 52
1.5免疫螢光染色 52
1.5-1 TNF-α之表現 52
1.5-2 p21之表現 52
1.5-3 Cyclin D1之表現 53
第二節 (+)-catechin在CDDP引起腎炎模型的藥效評估 61
2.1 尿中NAG、creatinine的含量分析 61
2.2 血清中BUN分析 61
2.3 組織病理PAS染色 62
2.4組織損傷量化分析 62
2.5免疫螢光染色 62
2.5-1 TNF-α之表現 62
2.5-2 p21之表現 63
2.5-3 Cyclin D1之表現 63
第三節 各種預防藥物在CDDP引起腎炎模型的藥效評估 71
3.1 尿中NAG、creatinine的含量分析 71
3.2 血清中BUN分析 71
3.3 組織病理PAS染色 72
3.4組織損傷量化分析 72
3.5免疫螢光染色 72
3.5-1 TNF-α之表現 72
3.5-2 p21之表現 73
3.5-3 Cyclin D1之表現 73
第六章 討論 81
第一節 綠茶濃縮劑在CDDP引起腎炎模型的藥效評估 81
第二節 (+)-catechin在CDDP引起腎炎模型的藥效評估 84
第三節 各種預防藥物在CDDP引起腎炎模型的藥效評估 86
第七章 結論 88
參 考 文 獻 90

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