【作者】 邢智远；

【导师】 宋修岐；

【作者基本信息】 青岛大学 ， 外科学， 2009， 硕士

【摘要】 目的:探讨不同剂量异臭椿烷对S₁₈₀肉瘤细胞小鼠皮下移植瘤的抑瘤作用。方法:建立S₁₈₀细胞小鼠皮下移植瘤动物模型,随机分为三组:空白对照组,阳性对照组和实验组。空白对照组给予纯食用油;阳性对照组给以环磷酰胺（25mg/kg）;实验组根据异臭椿烷用药剂量分为低剂量组（0.1mg/ml）、中剂量组（0.5mg/ml）、高剂量组（1.0mg/ml）。所有小鼠均连续给药5天后间隔两天为一疗程,共两疗程。停药后24小时处死小鼠,称取瘤重,计算抑瘤率;脱氧核糖核苷酸末端转移酶介导的缺口末端标记法（TUNEL）测定肿瘤组织凋亡指数（AI）;通过免疫组织化学方法观察肿瘤组织中Caspase-3与Bcl-2基因蛋白表达情况。结果:异臭椿烷能有效抑制肿瘤的发生发展,并且表现出明显的剂量依赖性,其中高剂量组及环磷酰胺组抑瘤率分别为40.0%,52.2%,与空白对照组比较均有统计学意义（P＜0.01）,但高剂量组与环磷酰胺组抑瘤率比较差异无统计学意义（P＞0.01）;中剂量和低剂量组抑瘤率分别为29.1%、24.7%,两者比较并无明显差异;异臭椿烷可以诱导肿瘤细胞凋亡,高、中、低三组凋亡指数分别为:11.04%、9.12%、8.85%;三者组间两两比较可以得出高剂量组凋亡指数与中、低剂量组指数差异具有统计学意义。中剂量组与低剂量组之间指数比较差异并无统计学意义;异臭椿烷可明显增高Caspase-3活性（阳:阴=18:3）,同时显著抑制Bcl-2活性（阳:阴=13:8）,尤以高剂量组变化最为显著。结论:异臭椿烷在体内可通过增加Caspase-3的活性和降低Bcl-2活性来诱导肿瘤细胞凋亡进而发挥抗肿瘤作用。更多还原

【Abstract】 Objective:To explore the anti-tumor effect of Isomalabaricane triterpenes on trsnsplant subcutaneous sarcoma in S₁₈₀ mice.Methods:The subcutaneous transplnantable tumor model of S₁₈₀ sarcoma in KM mice were established and divided at random into five groups:（0.1,0.5,1.0mg/ml） Isomalabaricane triterpenes, blank group（edible oil）and CTX（25mg / kg）group,each of which was composed of nine KM mice and received medicine（oil） in the following five days,interval for two days and continue five days again.The mouse was killed by dislocation of cervical spine surgery 24 hours after medication.The inhibition rate（TIR） was calculated to evaluate the anti-tumor effect by checking tumors’weight.The apoptotic index（AI） was determinated by the terminal deoxynucleotidyl transferase-mediated nick end labeling method（TUNEL）.The Caspase-3 with the Bcl-2 gene protein expression in tumor tissue was determinated by the Immunohistochemical method.Results:Isomalabaricane triterpenes can inhibit tumor occurrence and development effectively,with a dose-dependent manner,the high-dose group’s and Cyclophosphamide group’ s inhibition rate are 40.6%and 58.2%,respecting compared with blank control group,there were statistically significant （P＜0.01）.However,high-dose group and the cyclophosphamide group compared with each other the inhibition rate were no significant difference（P＞0.01）;Low-dose group’s and intermediate dose group’s inhibition rates were 29.1%and 24.7%,There is no significant difference between the two groups.Isomalabaricane triterpenes could induce tumor cell apoptosis,high,middle and low dose groups’apoptotic index were 11.04%、9.12%and 8.85%.Comparison of the three groups can be seen among high-dose group’s apoptotic index are more statistically significant than the middle dose group’s and low-dose group’s.Isomalabaricane triterpenes could increased Caspase-3 gene activity. At the same time,inhibiting the activity of Bcl-2 gene significantly,especially in the high dose groupConclusion:Isomalabaricane triterpenes can inhibit the S₁₈₀ sarcoma cell s growth.By increasing the activity of Caspase-3 and reduction of Bcl-2 activity induced apoptosis in tumor cells.更多还原