摘要
目的探讨刺参酸性黏多糖(stichopus japonicus acid mucopolysaccharide,SJAMP)联合5-FU对肝癌小鼠肿瘤生长及免疫功能的影响,了解其对化疗药的减毒增效作用。方法将60只小鼠随机分为正常对照组(生理盐水)、空白对照组(生理盐水)、5-FU组〔5-FU 20 mg/(kg·d)〕、SJAMP组〔SLAMP 25 mg/(kg·d)〕、SJAMP+低5-FU组〔SLAMP 25 mg/(kg·d)和5-FU 10 mg/(kg·d)〕和SJAMP+高5-FU组〔SLAMP 25 mg/(kg·d)和5-FU20mg/(kg·d)〕。除正常对照组外其他各组均于右腋皮下接种H22(Hepatocarcinoma22)细胞。接种后第2天开始给药,连续给药12d后处死小鼠,计算抑瘤率、胸腺指数和脾脏指数,ELISA检测血清TNF-α和IL-2含量,中性红法检测腹腔巨嗜细胞吞噬功能,CCK-8法测定脾脏淋巴细胞增殖能力,MTT法测NK细胞杀伤功能,流式细胞术检测小鼠外周血T细胞亚群。结果各干预组小鼠肿瘤生长明显受到抑制,SJAMP+高5-FU组抑瘤率(62.73%)高于5-FU组(55.53%),P=1.000。SJAMP组和SJAMP+低5-FU组小鼠脾脏指数显著高于其他组,P值均<0.05。SJAMP组和SJAMP+低5-FU组小鼠胸腺指数分别为(2.19±1.18)和(2.13±1.00)mg/g,高于5-FU组的(1.14±0.53)mg/g,P值分别为0.026和0.048;也高于SJAMP+高5-FU组的(1.07±0.49)mg/g,P值分别为0.011和0.020。各药物干预组TNF-α较空白对照组均降低,P值均<0.001。和空白对照组(33.27±6.13)相比,5-FU组(23.52±3.31)血清IL-2水平明显降低,P<0.001;SJAMP组(39.56±2.39)血清IL-2水平显著提高,P=0.001。与5-FU组相比,SJAMP组和联合用药组IL-2明显提高,P值均<0.001。SJAMP组和SJAMP+低5-FU组腹腔巨嗜细胞吞噬中性红能力显著高于正常对照组、空白对照组、5-FU组和SJAMP+高5-FU组,P值均<0.001;SJAMP+高5-FU组与5-FU组相比明显提高,P=0.012。SJAMP组和SJAMP+低5-FU组脾脏淋巴细胞增殖能力显著高于正常对照组(P值均<0.001)、空白对照组(P值均<0.001)、5-FU组(P值均<0.001)和SJAMP+高5-FU组(P值分别为0.005和0.011);SJAMP+高5-FU组与5-FU组相比明显提高,P=0.005。SJAMP组和SJAMP+低5-FU组NK细胞杀伤能力高于5-FU组,P值分别为0.002和0.030。空白对照组和5-FU组CD3+CD4+与CD3+CD8+细胞比值低于正常对照组(P值均<0.001)、SJAMP组(P值分别为0.001和<0.001)和SJAMP+低5-FU组(P值分别为0.003和0.024),SJAMP+高5-FU组高于5-FU组(P=0.329)。结论 SJAMP能够增强5-FU对肿瘤的抑制作用,减少5-FU对小鼠免疫功能的损伤。
OBJECTIVE To investigate the effects of SJAMP combined with 5 FU on tumor growth and immune function in Hepatocarcinoma22-bearing mouse and understand the synergism and attenuation effects on chemotherapy drug. METHODS The mice were randomly divided into normal group （Normal Saline）, model group （Normal Saline）, 5-FU group [5 FU 20 mg/（kg · d）], SJAMP group [SLAMP 25 mg/（kg · d）], SJAMP＋5-FU low-dose group [SLAMP 25 mg/（kg · d） and 5-FU 10 mg/（kg · d）], SJAMP＋5 FU high dose group ESLAMP 25 mg/（kg · d） and 5 FU 20 mg/（kg · d）·. Except normal group, other groups were injected H22 cells in the right axillary subcutaneous. The mice were intervened 12 days. Blood samples were drawn by excising eyeball and then all the mouse were sacrificed by cervical dislocation. The spleens and thymuses were removed under sterile conditions, and the spleen indexes and thymus indexes were calculated. TNF-α and IL-2 were detected by ELISA method. Neutral red method was used to detect macrophage phagocytosis. Spleen lymphocytes proliferation capability was assayed by CCK-8 method. NK cell function was detected by MTT method. T lymphocyte subsets were measured by flow cytometry. RESULTS The tumors in intervention group were significantly inhibited. The inhibition rate of tumor in SJAMP＋5 FU high-dose group（62.73%） was higher than that in 5-FU group（55.53 %） ,P= 1. 000. SJAMP group and SJAMP＋ 5-FU low-dose group were significantly higher than that in other groups, P〈0. 05. The thymus index in SJAMP group （2. 19± 1.18） mg/g and SJAMP＋5-FU low-dose group （2. 13±1.00） mg/g were higher than 5-FU group （1. 144±0.53） mg/g, P was respectively 0. 026 and 0. 048, and SJAMP＋5-FU high-dose group （1.07±0.49） mg/g, P was respectively 0. 011 and 0. 020. TNF-α in each intervention group were decreased, P=0. 000. Compared with model group （33.27±6.13） mg/g,IL 2 in 5-FU group （23.52±3.31） mg/g was decreased（P〈0. 001） and in SJAMP group （39.56±2.39） was increased （P=0. 001）. Compared with 5-FU group, IL2 in SJAMP group and combination group were increased, P〈0. 001. Peritoneal macrophage phagocytic function in SJAMP group and SJAMP＋5-FU low-dose group were significantly higher than normal group, model group, 5-FU group and SJAMP＋5-FU low-dose group, P〈0. 001. Compared with 5-FU group, SJAMP＋5-FU high dose group was significantly improved, P=0. 012. The spleen lymphocyte proliferation in SJAMP group and SJAMP＋5-FU low-dose group were significantly higher than in normal group, model group, 5-FU group （P%0. 001） and SJAMP＋5-FU low-dose group （P was respectively 0. 005 and 0. 011）; Compared with 5-FU group, SJAMP＋5-FU high dose group was increased significant ly, P=0. 005. The killing ability of NK cell in SJAMP group and SJAMP＋5-FU low-dose group were higher than that of 5-FU group, P was respectively 0. 002 and 0. 030. The ratio of CD3＋ CD4＋/CD3＋ CD8＋ in model group and 5-FU group were lower than normal group （P〈0. 001）, SJAMP group （P was respectively 0. 001 and d0. 001） and SJAMP＋5-FU low-dose group （P was respectively 0. 003 and 0. 024）. SJAMP＋5-FU high-dose group was higher than 5-FU group, P= 0. 329. CONCLUSION SJAMP could enhance the inhibitory effect of 5-FU on tumor and reduce the damage of 5-FU on immune function.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2015年第1期23-27,共5页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(81072295)
关键词
肝肿瘤
刺参酸性黏多糖
H22细胞
免疫活性
liver neoplasms
stichopus japonicus acid mucopolysaccharide
Hepatocarcinoma22
immunocompetence
