倍他司汀、西咪替丁對原發性肝癌大鼠肝微粒體CYP450的影響

陳艷平 張毅民 王乃平 韋錦斌

[摘要] 目的 研究倍他司汀和西咪替丁對原發性肝癌大鼠肝微粒體CYP450的影響。方法 以二甲基氨基偶氮苯誘發大鼠原發性肝癌,觀察倍他司汀和西咪替丁對大鼠第一相酶細胞色素P450的影響。結果整個實驗過程中,倍他司汀組和西咪替丁組大鼠細胞色素P450含量處于低水平并呈下降趨勢,與模型組比較,差異顯著(P<0.01)。結論 倍他司汀和西咪替丁可以抑制原發性肝癌大鼠肝微粒體細胞色素P450活性,從而抑制二甲基氨基偶氮苯在肝臟中的活化而降低他的致癌性及化學肝損傷。

[關鍵詞] 原發性肝癌;倍他司汀;西咪替丁;CYP450

[中圖分類號] R965[文獻標識碼] A[文章編號] 1004-8650(2009)06-023-03

The Effects of Betastine and Cimetidine on CYP450 of the Primary Liver Cancer of Wistar Rats

CHEN Yan-ping1, ZHANG Yi-min2, WANG Nai-ping3, WEI Jin-bin3

(1.Changsha Central Hospital Medical Section,HunanChangsha410005China;2.Fujian Provincial Corps Hospital, Chinese People's Armed Police Forces,Fuzhou350003China;3.Guangxi Medical University,GuangxiNanning530021,China)

[Abstract] ObjectiveTo study the effects of betastine and cimetidine on CYP450 of the primary liver cancer of Wister rats。MethodsDimethylamino-axobenzene was used to induce the rat liver cancer model in order to observe the influences of BET and CIM on the content of CYP450。Results During the experiment,the contents of CYP450 in betastine group and cimetidine group were maintained a low level and showed a tendency of decreasing;Compared to the model group,there was significant difference (P<0.01) between them。Conclusion Betastine and cimetidine can decrease the content of CYP450 of the primary liver cancer of Wister rats and also restrained dramatically activity of dimethylamino-axobenzene in the liver of rat and reduced the hepatocarcinoma rate.

[Key words] primary liver cancer;Betastine;Cimetidine;CYP450

CYP450是體內參與生物活性物質、激素和外來異物包括藥物代謝滅活的重要酶系,酶活性的高低直接影響到物質代謝的速度。

倍他司汀(betahistine, BET,抗眩啶)是組胺H1受體激動劑,能增加內耳、肝臟等組織血流量,臨床主要用于內耳眩暈癥[1]。經查新,國內外未見BET用于肝癌預防、治療的報道。王乃平等發現BET有預防、治療大鼠原發性肝癌的趨勢[2],同時,本課題組前期實驗發現BET為細胞色素P450抑制劑。

西咪替丁(cimetidine,CIM)是一種H2受體拮抗劑,同時也是一種經典的細胞色素P450的抑制劑,臨床上用于消化性潰瘍,近年發現他有抗腫瘤作用,可以抑制許多實驗性腫瘤的生長和轉移并可以延長動物的存活期,臨床上被用于抗腫瘤(如大腸癌)[3]。本實驗用二甲基氨基偶氮苯(DAB)誘導大鼠原發性肝癌模型,以期研究BET和CIM對原發性肝癌大鼠肝微粒體CYP450的影響。

1材料和方法

1.1動物

Wistar大鼠,雄性,體重(130±20)g,由廣西醫科大學實驗動物中心提供。

1.2試劑及藥物

BET[日本衛材株式會社,衛材(蘇州)制藥有限公司分……