丹参注射液联合5-氟脲嘧啶腹腔化疗抗鼠胃肿瘤的实验研究

Experimental Study on Resistance to Implanted Gastric Tumor in Rats with Radix Salviae Miltiorrhizae and 5-Fu by Intraperitoneal Chemotherapy

目的:观察丹参注射液对5-氟脲嘧啶(5-FU)抗肿瘤活性的增强作用及其对5-FU毒性和不良反应的减轻作用,为中药对抗肿瘤药的增效减毒作用提供实验依据。方法:应用Walker-256细胞株建立鼠种植性胃肿瘤模型,将60只Wistar雄性胃肿瘤大鼠随机分为3组:9.0 g/L氯化钠注射液(NS)组、5-FU组、5-FU+丹参组。接种后第7天,NS组每只每天腹腔注入NS,5-FU组每只每天腹腔注入5-FU,5-FU+丹参组每只每天腹腔注入5-FU+丹参,3组均连用5 d。于腹腔化疗结束后第7天每组处死10只大鼠。观察肿瘤体积抑制率、血常规、肝肾功能、细胞凋亡、大鼠生存时间。结果:①5-FU组和5-FU+丹参组鼠胃肿瘤生长明显缓慢,肿瘤体积较NS组明显减小(P(0.05,P(0.01),肿瘤体积抑制率分别为36.57%、59.44%(P(0.05);5-FU组和5-FU+丹参组鼠生存时间明显延长,生存时间延长率分别为23.7%、38.7%(P(0.05)。②与NS组相比,5-FU组和5-FU+丹参组外周血WBC、PLT明显减少,血清ALT、AST、Cr、BUN明显升高,差异均有显著性(P(0.05,P(0.01);与5-FU组相比,5-FU+丹参组WBC、PLT显著升高,而ALT、AST、Cr、BUN显著下降(P(0.05,P(0.01)。③与NS组相比,5-FU组和5-FU+丹参组凋亡面积增大,光密度明显升高(P(0.05,P(0.01);而5-FU+丹参组与5-FU组比较,差异也有显著性(P(0.05,P(0.01)。结论:丹参注射液可增强5-FU诱导肿瘤细胞分化与凋亡,并能减轻5-FU所致的骨髓抑制和肝肾功能损害。

Objective： To observe the enhanced anti-neoplasm efficacy and the reduced toxic and side effects of 5-fluoroura （5-Fu） by intraperitoneal chemotherapy （IPC） with combined administration of radix salviae miltiorrhizae （RSM） in rats bearing implanted gastric tumor, and provide an experimental evidence for the synergism and attenuation effects of traditional Chinese medicine in combination with antineoplastic agents. Methods： Sixty Wistar rats were implanted gastric tumor with the malignant tumor cell line Walker-256 and then divided randomly into 3 groups： 9.0 g/L sodium chloride （NS） group,5-Fu group, RSM and 5-Fu group, seven days after IPC, 10 rats in each group were executed to examine tumor volume, and the levels of WBC, PLT, ALT, AST, Cr and BUN in rat serum. The apoptosis were measured by terminal deoxynuleotidyl transferase mediated nick and labeling （TUNEL） methods, and its area and optical density processed automatically by the IMS cell image analyzing system. The other rats were observed till their death to calculate the survival time extending ratio. Results： （1）The tumor volume in the 5-Fu group and RSM ＋ 5-Fu group dwindled in comparison with that in the NS group（P 〈0. 05 ,P 〈 0. 01 ）, the tumor volume inhibition ratio in the 5-Fu group and RSM ＋ 5-Fu group were 36.57%, 59.44% respectively （P 〈 0. 05 ）. The survival time in the two experimental groups was obviously longer than that in NS group （P 〈 0. 01）, the survival time in RSM ＋ 5-Fu group was longer than that in 5-FU group（P 〈 0. 05）, the survival time extending ratio in the 5-Fu group and RSM ＋ 5-Fu group were 23.7%, 38.7% respectively（ P 〈 0. 05 ）. （2）Seven days after IPC , the levels of WBC, PLT in the two experimental groups were significantly lower than those in NS group, and the levels of ALT, AST, Cr, BUN were higher（P 〈 0. 05 ,P 〈 0. 01 ） ;But the levels of WBC, PLT in RSM ＋5-Fu group were higher than those in 5-FU group, and the levels of ALT, AST, Cr and BUN were lower（P 〈 0. 05 ,P 〈 0. 01 ）. （3）The apoptosis area and optical density in the two experimental groups were significantly increased compared with those in NS group（P 〈 0. 05,P 〈 0. 01） ,and they were significantly increased in RSM ＋ 5-Fu group compared with those in 5-FU group（P 〈0. 05 ,P 〈0. 01）. Conclusion： RSM could enhance the effects of 5-FU in inducing apoptosis and inhibiting the tumor growth, and reduce the toxic and side effects of 5-FU.