Yao Qinghua, Ye Xiaozheng, Wang Lu, Gu Jianzhong, Fu Ting, Wang Yun, Lai Yuebiao, Wang Yuqi, Wang Xian, Jin Hongchuan, Guo Yong
Department of Oncology, The First Affiliated Hospital of Zhejiang Traditional Chinese Medical University Hangzhou, Zhejiang Province, China.
Int J Clin Exp Pathol. 2013 Oct 15;6(11):2342-9. eCollection 2013.
Chemotherapy is one of most important treatments for human cancers. However, side effects such as intestine dysfunction significantly impaired its clinical efficacy. This study aimed to investigate the protective effect of Curcumin on chemotherapy-induced intestinal dysfunction in rats.
Sixty healthy Wistar rats were randomly divided into control group (normal saline), 5-FU group and 5-FU+Curcumin group. The weight, serum level of endotoxin, DAO and D-lactate were determined. The pathological change of intestinal mucosa structure was studied under light microscopy and electron microscopy. The expression of Bax, Bcl-2 and Caspase-3 were assessed by immunohistochemical staining.
The Curcumin intragastrically administrated obviously reduced 5-FU-induced weight-loss. 5-FU induced dramatic increase of serum endotoxin, D-lactate and D-Amino-Acid Oxidase (DAO) that were significantly reversed by Curcumin treatment. Meanwhile, 5-FU-induced-damage to intestinal mucosa structure was markedly recovered by Curcumin. The expression of Bax and Caspase-3 were dramatically increased after 5-FU treatment (p<0.01) and Curcumin treatment significantly reduced Bax expression (p<0.05) but had only a moderate effect on reducing caspase-3 expression (p>0.05). Interestingly, Bcl-2 expression was low in control group but increased after 5-FU treatment (p>0.05) and Curcumin treatment further stimulated Bcl-2 expression (p<0.05).
Curcumin can significantly reverse chemotherapy-induced weight-loss, increase of serum endotoxin, D-lactate and DAO and damage to intestinal mucosa structure. Curcumin also reduced the expression of pro-apoptotic Bax but stimulated anti-apoptotic Bcl-2 to attenuate 5-FU-induced apoptosis of intestinal epithelial cells. The clinical administration of Curcumin may improve chemotherapy-induced intestinal dysfunction, thus increasing the clinical efficacy of chemotherapy.
化疗是人类癌症最重要的治疗方法之一。然而，诸如肠道功能障碍等副作用显著损害了其临床疗效。本研究旨在探讨姜黄素对大鼠化疗诱导的肠道功能障碍的保护作用。
将60只健康的Wistar大鼠随机分为对照组（生理盐水）、5-氟尿嘧啶组和5-氟尿嘧啶+姜黄素组。测定体重、血清内毒素水平、二胺氧化酶（DAO）和D-乳酸水平。在光学显微镜和电子显微镜下研究肠黏膜结构的病理变化。通过免疫组织化学染色评估Bax、Bcl-2和半胱天冬酶-3的表达。
胃内给予姜黄素明显减轻了5-氟尿嘧啶诱导的体重减轻。5-氟尿嘧啶导致血清内毒素、D-乳酸和二胺氧化酶显著升高，而姜黄素治疗可显著逆转这些变化。同时，姜黄素显著恢复了5-氟尿嘧啶诱导的肠黏膜结构损伤。5-氟尿嘧啶治疗后Bax和半胱天冬酶-3的表达显著增加（p<0.01），姜黄素治疗显著降低了Bax的表达（p<0.05），但对降低半胱天冬酶-3的表达只有中等程度的影响（p>0.05）。有趣的是，对照组中Bcl-2的表达较低，但5-氟尿嘧啶治疗后升高（p>0.05），姜黄素治疗进一步刺激了Bcl-2的表达（p<0.05）。
姜黄素可显著逆转化疗诱导的体重减轻、血清内毒素、D-乳酸和二胺氧化酶升高以及肠黏膜结构损伤。姜黄素还降低了促凋亡蛋白Bax的表达，但刺激了抗凋亡蛋白Bcl-2的表达，以减轻5-氟尿嘧啶诱导的肠上皮细胞凋亡。姜黄素的临床应用可能改善化疗诱导的肠道功能障碍，从而提高化疗的临床疗效。
