二烯丙基二硫对D-氨基半乳糖/脂多糖所致小鼠急性肝损伤的保护作用

Protective effect of diallyl disulfide on acute liver injury induced by D-galactosamine/lipopolysaccharide

目的研究二烯丙基二硫(diallyl disulfide,DADS)对D-氨基半乳糖/脂多糖(D-galactosamine/lipopolysaccharide,D-gal/LPS)诱导的小鼠急性肝损伤是否有保护作用。方法SPF级雄性ICR小鼠72只,随机分为6组:对照组,DADS对照组,D-gal/LPS模型组和DADS低、中、高剂量干预组(DADS+D-gal/LPS),每组12只。DADS对照组、DADS低、中、高剂量干预组小鼠分别灌胃给予不同剂量的DADS(80、20、40和80 mg/kg·bw),给予DADS 1 h后,DADS干预组和D-gal/LPS模型组小鼠腹腔注射D-gal(500 mg/kg·bw)/LPS(10μg/kg·bw),8 h后称量小鼠体重,取血并分离血清,检测血清丙氨酸转氨酶(alanine aminotransferase,ALT)、天冬氨酸转氨酶(aspartate aminotransferase,AST)、乳酸脱氢酶(lactate dehydrogenase,LDH)活力和总胆红素(total bilirubin,TBil)的水平;取出肝脏,称重并计算肝脏系数;将肝左叶制作石蜡切片,通过苏木素-伊红(HE)染色对肝进行组织病理学检查。结果与对照组相比,DADS对照组无明显异常,各组小鼠的肝脏系数差异无统计学意义;D-gal/LPS模型组小鼠的存活率为92%,血清ALT、AST、Tbil和LDH水平明显升高(P<0.05),HE染色显示肝小叶出现大面积的出血性坏死,同时可见嗜酸性小体,表明肝细胞发生凋亡。与D-gal/LPS模型组相比,20、40和80 mg/kg·bw的DADS干预组小鼠存活率均为100%;ALT、AST活力和Tbil含量均明显降低(P<0.05),其中给予80 mg/kg·bw的DADS干预后ALT、AST、Tbil和LDH分别降低了88.5%、84.2%、35.3%和77.2%;HE染色示肝脏出血性坏死区域明显减少,仅20 mg/kg·bw的DADS干预组有局部肝细胞坏死灶,40和80 mg/kg·bw的DADS干预组已无明显肝细胞坏死。结论DADS对D-gal/LPS诱导的急性肝损伤有明显的保护作用。

Objective To study whether diallyl disulfide(DADS)has protective effect on acute liver injury induced by D-galactosamine(D-gal)/lipopolysaccharide(LPS)in mice.Methods Seventy-two SPF-grade male ICR mice were randomly divided into six groups:control group,DADS control group,D-gal/LPS model group,DADS low,medium and high dose intervention group(DADS+D-gal/LPS),12 mice in each group.Mice in DADS control group,DADS low,medium and high dose intervention group were given different doses of DADS(80,20,40 and 80 mg/kg·bw)by gavage respectively.After one hour of DADS administration,mice in DADS low,medium and high dose intervention group and mice in D-gal/LPS model group were intraperitoneally injected with D-GAL(500 mg/kg·bw)/LPS(10μg/kg·bw)and weighed eight hours later.Blood was collected and serum was separated,and the levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH)and total bilirubin(TBil)were detected.The liver was weighed,and calculated the liver ratio.The left lobe of liver was made into paraffin sections,and the liver was examined by HE staining.Results Compared with the control group,there was no obvious abnormality in DADS control group.There was no significant difference in liver coefficient among different groups.The survival rate of mice in D-gal/LPS model group was 92%,and the levels of ALT,AST,Tbil and LDH in serum were significantly increased(P<0.05).HE staining showed massive hemorrhagic necrosis of liver lobules and eosinophilic body(indicating hepatocyte apoptosis).Compared with D-gal/LPS model group,the survival rate of 20,40 and 80 mg/kg·bw DADS intervention group was 100%;ALT,AST activity and Tbil content decreased significantly(P<0.05),among which ALT,AST,Tbil and LDH decreased by 88.5%,84.2%,35.3%and 77.2%in 80 mg/kg·bw intervention group,respectively.H&E staining showed that the area of hepatic hemorrhagic necrosis was obviously reduced,only 20 mg/kg·bw DADS intervention group had local hepatocyte necrosis focus,and the 40 and 80 mg/kg·bw DADS intervention groups had no obvious hepatocyte necrosis.Conclusion DADS has obvious protective effect on acute liver injury induced by D-gal/LPS.