沙利度胺对四氯化碳致小鼠急性肝损伤的影响

Effect of Thalidomide on Acute Liver Injury Induced by Carbon Tetrachloride in Mice

目的探讨沙利度胺对急性肝损伤模型小鼠的影响。方法将48只C57BL/6小鼠随机分为正常对照组(等体积生理盐水)、模型组(等体积生理盐水)、复方甘草酸苷组(0.035 mg/g)及沙利度胺低、中、高剂量组(0.01,0.03,0.05 mg/g),各8只。腹腔注射0.6%四氯化碳(CCl_(4),0.01 mL/g)以复制急性肝损伤小鼠模型,建模前12 h及建模后12 h、24 h时均灌胃给予相应药物或生理盐水。称定肝组织质量及体质量,并计算肝指数。以苏木精-伊红(HE)染色,观察小鼠肝组织病理形态变化。检测小鼠血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平,酶联免疫吸附试验法检测小鼠肝组织匀浆中肿瘤坏死因子-α(TNF-α)表达水平,Western blot法检测小鼠肝组织匀浆中CD68蛋白表达水平。结果与模型组比较,复方甘草酸苷组及沙利度胺中剂量组小鼠肝细胞坏死、炎性浸润程度减轻;复方甘草酸苷组及沙利度胺低、中、高剂量组小鼠肝指数及血清中ALT、AST水平显著降低(P<0.05);复方甘草酸苷组及沙利度胺中、高剂量组小鼠肝组织匀浆中TNF-α表达水平显著降低(P<0.01);复方甘草酸苷组及沙利度胺中剂量组小鼠肝组织匀浆中CD68蛋白表达水平显著降低(P<0.05)。结论沙利度胺可显著改善CCl_(4)诱导的小鼠急性肝损伤,其作用机制可能与抑制转氨酶活性及CD68蛋白的表达有关。

Objective To investigate the effect of thalidomide on the acute liver injury model mice.Methods Forty-eight C57BL/6 mice were randomly divided into the normal control group(equal volume of physiological saline),the model group(equal volume of physiological saline),the compound glycyrrhizin group(0.035 mg/g),the thalidomide low-,medium-,and high-dose groups(0.01,0.03,0.05 mg/g),with eight mice in each group.The mice were intraperitoneally injected with 0.6%carbon tetrachloride(CCl_(4),0.01 mL/g)to replicate the acute liver injury model,corresponding drugs or physiological saline were given by gavage at 12 h before modeling and at 12,24 h after modeling.The liver tissue mass and body mass were weighed,and the liver index was calculated.The pathological change in liver tissue of mice was observed by the hematoxylin-eosin(HE)staining.The alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels in mouse serum were detected;the expression level of tumor necrosis factor-α(TNF-α)in liver tissue homogenates of mice was detected by the enzyme-linked immunosorbent assay;the expression level of CD68 protein in liver tissue homogenates of mice was detected by the Western blot.Results Compared with those in the model group,the liver cell necrosis and inflammatory infiltration in the compound glycyrrhizin group and thalidomide medium-dose group relieved;the liver index and serum ALT and AST levels in the compound glycyrrhizin group and thalidomide low-,medium-,and high-dose groups significantly decreased(P<0.05);the expression level of TNF-αin the liver tissue homogenates in the compound glycyrrhizin group and thalidomide medium-,and high-dose groups significantly decreased(P<0.01);the expression level of CD68 protein in the liver tissue homogenates in the compound glycyrrhizin group and thalidomide medium-dose group significantly decreased(P<0.05).Conclusion Thalidomide can significantly improve the CCl_(4)-induced acute liver injury in mice,and its mechanism may be related to the inhibition of transaminase activity and CD68 protein expression.