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茶对大鼠肝脏癌前病变及细胞周期调节因子的影响。

Effects of tea on preneoplastic lesions and cell cycle regulators in rat liver.

作者信息

Jia Xudong, Han Chi, Chen Junshi

机构信息

Institute of Nutrition and Food Hygiene, Chinese Academy of Preventive Medicine, Beijing, 100050, China.

出版信息

Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1663-7.

Abstract

The effects of tea polyphenols and tea pigments on rat liver precancerous lesions and some cell cycle regulators were studied. A modified Solt-Farber model in rats was established by multiple low-dosage of N-nitrosodiethylamine (NDEA) i.p. injections, followed by i.p. CCl(4) injection and partial hepatectomy. Sixty male Wistar rats were randomly divided into four groups: positive control group, two tea-treated groups, and negative control group. Rats in tea-treated groups were given tea polyphenols (0.1%) and tea pigments (0.1%) in drinking fluid during the whole experiment. The number and area of glutathione S-transferase P (GST-P)-positive foci in the rat liver were used as biomarkers of precancerous liver lesions. Western blotting assay was carried out to detect the expression of cyclin D1, CDK4, and P21(WAF1/CIP1) on whole liver extract. At the end of the experiment (56 days), the number and area of GST-P-positive foci in liver increased significantly in carcinogen-administered positive control group, whereas no GST-P-positive foci were found in the negative control group in which animals did not receive carcinogen exposure. The number and area of GST-P-positive foci in tea-treated, carcinogen-exposed groups were significantly reduced as compared with the positive control group. It was also found that the expression of P21(WAF1/CIP1) was significantly induced and the expression of cyclin D1 and CDK4 was significantly inhibited in tea-treated groups. These results suggest that tea polyphenols and tea pigments are effective in preventing the precancerous liver lesions in rats, and modulation of cell cycle by regulating cell cycle regulators may be a possible mechanism.

摘要

研究了茶多酚和茶色素对大鼠肝前病变及一些细胞周期调节因子的影响。通过腹腔注射多次低剂量的N-亚硝基二乙胺(NDEA)建立大鼠改良的Solt-Farber模型,随后腹腔注射四氯化碳(CCl₄)并进行部分肝切除术。60只雄性Wistar大鼠随机分为四组:阳性对照组、两个茶处理组和阴性对照组。在整个实验过程中,茶处理组的大鼠饮用含茶多酚(0.1%)和茶色素(0.1%)的液体。大鼠肝脏中谷胱甘肽S-转移酶P(GST-P)阳性灶的数量和面积用作肝前病变的生物标志物。采用蛋白质免疫印迹法检测全肝提取物中细胞周期蛋白D1、细胞周期蛋白依赖性激酶4(CDK4)和P21(WAF1/CIP1)的表达。实验结束时(56天),给予致癌物的阳性对照组肝脏中GST-P阳性灶的数量和面积显著增加,而未接受致癌物暴露的阴性对照组未发现GST-P阳性灶。与阳性对照组相比,茶处理的致癌物暴露组中GST-P阳性灶的数量和面积显著减少。还发现茶处理组中P21(WAF1/CIP1)的表达显著诱导,细胞周期蛋白D1和CDK4的表达显著抑制。这些结果表明,茶多酚和茶色素可有效预防大鼠肝前病变,通过调节细胞周期调节因子来调控细胞周期可能是一种潜在机制。

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