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半夏泻心汤对依立替康致小细胞肺癌荷瘤鼠腹泻的改善作用及机理研究
Study on the Improvement and Mechanism of Banxiaxiexin Decoction against Irinotecan-induced Diarrhea in Nude Mice Bearing the Tumor of Human Small-cell Lung Cancer
【作者】 卢红阳; 马胜林; 郭勇; 蔡菊芬; 王晓稼; 叶威武;
【Author】 LU Hongyang~1,MA Shenglin~1,GUO Yong~2,CAI Jufen~1,WANG Xiaojia~1,YE Weiwu~1 (1.Zhejiang Cancer Hospital,Hangzhou 310022,Zhejiang,China; 2.Zhejiang Traditional Hospital,Hangzhou 310006,Zhejiang,China)
【摘要】 目的:观察半夏泻心汤对依立替康(Irinotecan,CPT-11)致小细胞肺癌(Small-celllung cancer,SCLC)荷瘤鼠腹泻的改善作用并初步研究其作用机理。方法:取荷瘤鼠,灌胃给予半夏泻心汤,连续8d。第3d开始尾静脉注射CPT-1 1(35mg/kg/d)连续4d,记录荷瘤鼠每天腹泻情况,第8天摘眼球取血并处死。光学显微镜下观察结肠和回肠组织病理学形态;免疫组织化学法检测结肠组织中环氧合酶-2(Cyclooxygenase-2,COX-2)表达水平;酶联免疫吸附法(Enzyme-linked immunosorbent assay,ELISA)检测结肠组织中白细胞介素-15(Interleukin-15,IL-15)浓度;可见紫外分光光度法检测结肠组织中β-葡萄糖醛酸酶(β-Glucoronidase,β-GCD)浓度;高效液相色谱法(HPLC)检测结肠组织和血浆7-乙基-10-羟基喜树碱(7-Ethyl-10-Hydroxy-CPT,SN-38)浓度。结果:空白组腹泻积分最高,中、高剂量组与空白组比较有显著性差异(P<0.05)。高剂量组结肠组织COX-2表达低于空白组(P<0.05),其余各组差异不明显。各给药组结肠组织IL-15和β-GCD浓度与空白组比较均无显著性差异(P>0.05)。高剂量组结肠组织SN-38浓度与空白组比较有显著性差异(P<0.05),其余各组差异不明显(P>0.05)。各给药组SN-38血药浓度与空白组比较均无显著性差异(p>0.05)。结论:半夏泻心汤能在一定程度上改善CPT-11致SCLC荷瘤鼠的腹泻,其作用与抑制结肠组织COX-2表达,降低结肠组织中SN-38浓度有关。
【Abstract】 Objective:To observe the improvement and mechanism of Banxiaxiexin decoction against irinotecan(CPT-11)-induced diarrhea in nude mice bearing the tumor of human small-cell lung cancer.Methods:Banxiaxiexin decoction was i.g.administered to mice for eight days.CPT-11 was given i.v.at the dose of 35 mg/kg/d from the 3rd to the 6th day.Diarrhea of each mouse was recorded everyday.And their blood was obtained from eyeballs followed by killing at the 8th day.The pathological changes of colon and ileum were observed under microscope,and Cyclooxygenase-2(COX-2) of colon was detected by immunohistochemical methods.Enzyme-linked immunosorbent assay(ELISA) and UV-visible spectrophotometry were used to analyze the concentrations of the interleukin-15(IL-15) andβ-Glucoronidase(β-GCD) in colon,respectively.High performance liquid chromatography(HPLC) was applied to detect the concentration of 7-Ethyl-10-Hydroxy-CPT(SN-38) in blood plasma and colon.Results:The diarrhea of the blank group was more serious compared to the middle and high dose groups(P<0.05).The expression of COX-2 in colon tissue was lower in the high dose group than in the blank group(P<0.05).There were no significant differences of the concentrations of IL-15 andβ-GCD in colon between each drug administered group and the blank group.The concentration of SN-38 in colon tissue was lower in the high dose group than the blank group(P<0.05).There was no significant difference of the concentration of SN-38 in blood between each drug administered and the blank group.Conclusion:Banxiaxiexin decoction could improve the diarrhea induced by CPT-11 in Nude Mice Bearing the Tumor of Human Small-cell Lung Cancer.The improvement was related to the reduction of the concentration of SN-38 in the colon and inhibition of the COX-2 expression in the colon tissue.
- 【会议录名称】 2009医学前沿论坛暨第十一届全国肿瘤药理与化疗学术会议论文集
- 【会议名称】2009医学前沿论坛暨第十一届全国肿瘤药理与化疗学术会议
- 【会议时间】2009-04-09
- 【会议地点】中国云南昆明
- 【分类号】R734.2
- 【主办单位】中国工程院医药卫生学部、中国抗癌协会抗癌药物专业委员会、中国药理学会肿瘤药理专业委员会