摘要
目的探讨二烯丙基硫醚(diallyl sulfide,DAS)对二乙基亚硝胺(diethylnitrosamine,DEN)和四氯化碳(carbon tetrachloride,CCl4)诱导的小鼠肝癌合并肝纤维化的干预效果。方法 14日龄雄性ICR小鼠随机分为4组:正常对照组、模型组(DEN+CCl4)、DAS低剂量干预组和DAS高剂量干预组,每组15只。除对照组外,小鼠出生第14天时腹腔注射DEN(25 mg/kg)诱发小鼠肝癌;小鼠出生6周时,每周腹腔注射CCl4(1 ml/kg)2次,持续给予14周诱发肝纤维化。DAS低和高剂量干预组在腹腔注射CCl4前2小时分别灌胃DAS(20或40 mg/kg),每天1次,连续给药16周。检测血清丙氨酸氨基转移酶(Alanine transaminase,ALT)、天门冬氨酸氨基转移酶(Aspartate transaminase,AST)、γ-谷氨酰转肽酶(Gammaglutamyl transferase,GGT)的活力和甲胎蛋白(alpha-fetoprotein,AFP)的含量,比较各组小鼠肝脏系数、肝脏表面癌结节数目,并对肝脏进行病理组织学检查及天狼猩红染色。结果与正常对照组相比,模型组小鼠肝脏系数明显增加,血清ALT、AST、GGT的活力升高(P<0.05),AFP含量显著增加(P<0.05);与模型组相比,DAS干预组小鼠各项指标均明显改善(P<0.05)。DAS干预后肝脏系数明显降低、肝脏表面增生癌结节数目明显减少(P<0.05)。其中高剂量干预组小鼠肝脏表面癌结节数目和血清中AFP含量显著低于低剂量干预组(P<0.05)。HE染色和天狼猩红染色结果表明,与模型组相比,DAS低、高剂量干预组小鼠肝组织切片中肿瘤区减少、细胞核异型性降低,肝纤维化明显减轻。结论 DAS的干预显著抑制了DEN和CCl4诱发的小鼠肝癌合并肝纤维化的进展。
Objective To understand the intervention effects of diallyl sulfide(DAS) on hepatocarcinoma complicated with hepatic fibrosis induced by diethylnitrosamine(DEN) and carbon tetrachloride(CCl4) in mice. Methods Male ICR mice aged14-day were randomly divided into four groups,15 per group,normal control group, model group(DEN+CCl4), low dose and high dose of DAS intervention group. In addition to the mice in control group, all the mice received single intraperitoneal(i.p.)injection of DEN(25 mg/kg) to induce hepatocarcinoma at the 14 th day after birth.In order to induce the liver fibrosis, the mice were i.p. injected CCl4(1 ml/kg) twice a week for consecutive 14 weeks at the age of six weeks. 2 h before CCl4 injection, the mice were gavaged DAS(20 or 40 mg/kg) for 16 weeks(once a day) in DAS low and high dose intervention groups. At the end of experiment, the blood and liver were collected. The activities of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), gamma-glutamyl transpeptidase(GGT) and the content of alpha-fetoprotein(AFP) were measured. The changes of liver ratio, the number of cancer nodule on the liver surface, the histopathology and liver fibrosis were evaluated.Results Compared with the normal control group, the liver ratio, the activities of ALT, AST, GGT and the content of AFP in the serum were significantly increased in model group(P <0.05);Compared with the model group, all the indexes in the DAS intervention groups were significantly improved(P<0.05). The liver ratio and the number of cancer nodule on the liver surface decreased significantly after DAS treatment(P<0.05). The number of cancer nodule and AFP content in serum of the high-dose DAS intervention group were significantly lower than those of the low-dose DAS intervention group(P<0.05). HE and sirius red staining results showed the tumor area reduction, the nuclear atypia decrease and the liver fibrosis reduction in the low-dose and high-dose DAS intervention groups compared with model group. Conclusion The intervention of DAS may significantly inhibit the progression of hepatocarcinoma complicated with hepatic fibrosis induced by DEN and CCl4 in micee.
作者
张翠丽
曾涛
赵秀兰
宋福永
谢克勤
ZHANG Cui-li;ZENG Tao;ZHAO Xiu-lan;Song Fu-yong;XIE Ke-qin(College of Public Health,Shandong University,Ji’nan,Shandong 250012,China)
出处
《环境与健康杂志》
CAS
北大核心
2020年第3期213-215,共3页
Journal of Environment and Health
基金
山东省重点研发计划(2017GSF18181)
关键词
二烯丙基硫醚
二乙基亚硝胺
四氯化碳
肝癌
肝纤维化
Diallyl sulfide
Diethylnitrosamine
Carbon tetrachloride
Hepatocarcinoma
Hepatic fibrosis
