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  • 學位論文

不同粒徑丹參的萃取物在順氯氨鉑引發之腎毒性於純系小鼠的藥效評估

Effects of extracts from different particle sizes of Salvia miltiorrhiza on cisplatin-induced nephrotoxicity in inbred mice

指導教授 : 陳世銘
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摘要


癌症是全球導致死亡的主要原因之一。在台灣,癌症更是連續二十九年蟬聯十大死因之首。因此,癌症的預防與治療日漸成為全球醫療發展的重要目標。順氯氨鉑 (cis-diamminedichloroplatinum (II);CDDP) 在臨床上廣泛用於固體癌症的化學治療,對頭頸癌、食道癌、卵巢癌、睪丸癌、膀胱癌、子宮頸癌等癌症的單一或合併治療都有良好的效果,但CDDP 引起的腎毒性卻成為限制其使用的主因之一。丹參 (Salvia miltiorrhiza) 在中醫常作為活血去瘀、調經止痛、養血安神與涼血消廱的用藥。近幾年,丹參被發現有抗氧化與抗發炎等功效,且具有抗癌的活性,故也逐漸在西方醫學中受到重視。 本研究的目的為比較由不同粒徑丹參所抽提的萃取物,探討其對 CDDP 引起腎毒性的預防效果。實驗以六週齡的BALB/c 雌鼠作為實 驗動物,以腹腔注射的方式給予CDDP 5 mg/kg/day,藉以引起腎炎, 並在投予CDDP 前5 天開始經口投予丹參粗粉與細粉的萃取物 (300 mg/kg/day、600 mg/kg/day、900 mg/kg/day),以評估其對於預防CDDP引起腎炎的療效。結果顯示, 丹參粗細粉萃取物對於N-acetyl-β-D-glucosaminidase (NAG)、尿中肌酸酐 (urine creatinine)、 尿蛋白 (urine protein) 與血中尿素氮 (BUN) 皆有不同程度的改善效果;腎組織損傷相較於對照組也有明顯減緩的趨勢。免疫螢光染色也觀察到投予丹參粗細粉萃取物的組別,TNF-α 表現量明顯下降,p21及PCNA 的表現也有不同程度的增加;但在相同劑量下,丹參粗粉 與細粉萃取物間對於各項指標的改善並沒有統計上的差異。 綜合本實驗的結果可推論,經口投予丹參粗細粉萃取物可透過抑 制發炎反應、降低氧化壓力等機制來保護腎臟,減低使用CDDP 對腎臟造成的傷害。但未來仍需更多實驗來佐證不同粒徑丹參的萃取物對於腎臟的保護效果是否會有差異。

關鍵字

cisplatin 腎毒性 丹參TNF-α p21 PCNA

並列摘要


Cancer is a global concern because it is a leading cause of death worldwide. In Taiwan, cancer has ranked the number-one cause of death for many years. In recent years, prevention and treatment for cancer become an important issue in the world. Cisplatin (cis-diamminedichloroplatinum (II);CDDP) is one of the most widely used antineoplastic agents in the treatment of solid tumor and haematological malignancies. However, side effects in normal tissues and organs, notably nephrotoxicity in the kidneys, limit the use of CDDP. Danshen, the dried root of Salvia miltiorrhiza, is a commonly used traditional Chinese medicine (TCM) for improving body function. In recent years, danshen has been shown to reduce reactive oxygen species (ROS) for antioxidative effect. And it can suppressed the expression of pro-inflammatory cytokines to decrease inflammatory reactions. The aim of this study is to investigate the kidney damage caused by CDDP administration and to evaluate the effects of treatment with prevention drugs. The prevention drugs were extracted from different particle sizes of danshen. In this animal study, six-week-old female BALB/c mice were administered with 5 mg/kg/day of CDDP intraperitoneally (i.p.) for 5 days. Prevention drugs including 300, 600, 900 mg/kg/day extracts from different particle sizes of danshen were given orally once daily from 5 days before CDDP administration, respectively. The result reveals the treatment groups showed improvements in urine N-acetyl-β-D-glucosaminidase (NAG), urine creatinine excretion, urine protein and blood urea nitrogen (BUN) at different levels. And the treatment groups ameliorated CDDP-induced renal morphological damages, reduced tumor necrosis factor-α (TNF-α) in injury tissues, and increased the expression of p21, proliferating cell nuclear antigen (PCNA) in renal cells as well (p < 0.05). But the efficacy has no significant differents between the extracts from different particle sizes of danshen. This study demonstrated that extracts of danshen might attenuated CDDP-induced nephrotoxicity. But the particle sizes might not be a powerful factor to affect the efficacy. Nevertheless, it may need more future studies to confirm the renoprotective effect between the extracts from different particle sizes of danshen.

並列關鍵字

cisplatin nephrotoxicity danshen TNF-α p21 PCNA

參考文獻


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