虎杖苷对小鼠脓毒症模型ALT、AST、TNF-α及COX-2的影响

作者	单位	E-mail
李晓会,吴孟娇,张丽娜,郑佳佳
万敬员	重庆医科大学重庆市生物化学与分子药理学重点实验室（重庆400016）	jywan@cqmu.edu.cn

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中文摘要:

目的研究虎杖苷对小鼠脓毒症致急性肝损伤的保护作用，并初步探讨其机制。方法采用盲肠结扎穿孔（cecal ligation and puncture，CLP）小鼠脓毒症模型，并设假手术对照组。在CLP手术前1 h，采用不同剂量虎杖苷（50、100、300 mg/kg）干预，随后每6 h观察小鼠一般情况，24 h后处死存活小鼠，收集血清和肝组织样本。分别采用比色法检测血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）活性；采用酶联免疫法检测血清肿瘤坏死因子-α （tumor necrosis factor-alpha，TNF-α）含量；采用免疫印迹法检测肝组织环氧合酶-2 （cyclooxygenase-2，COX-2）表达；并取部分肝组织进行病理组织学分析。结果 CLP后24 h，小鼠死亡率高达50%，生化指标和肝脏病理显示病变明显，模型成功率达90%，相对于假手术组，血清ALT、AST活性、TNF-α水平和肝组织中COX-2蛋白表达显著升高（P<0.01）；虎杖苷呈剂量依赖地改善脓毒症诱导的死亡率，抑制ALT、AST活性和TNF-α升高（P<0.05），降低肝组织中COX-2表达，减轻肝脏病理损伤。结论虎杖苷有效地保护脓毒症诱导的急性肝损伤，其作用机制可能通过抑制TNF-α生成和COX-2的表达。

英文摘要:

Objective To investigate the protective effects of polydatin on sepsis-induced acute liver injury （ALI） in mice， and to preliminarily study its mechanisms. Methods The sepsis model was established using cecal ligation and puncture （CLP）. A sham-operation control group was also set up. Polydatin （50， 100， and 300 mg/kg， respectively） was administrated to mice 1 h before CLP. The survival and liver injury were evaluated subsequently per 6 h after CLP. The survived mice were scarified 24 h later. The serum and the liver tissue sample were collected. The serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected by colorimetric method. The content of tumor necrosis factor-alpha （TNF-α） was assayed by ELISA. The cyclooxygenase-2 （COX-2） expression in the liver tissue was detected by Western blot. The pathological changes of the hepatic tissue were analyzed by hematoxylin and eosin stain. Results The mortality of mice reached as high as 50% at 24 h after CLP. The biochemical indices and the pathological changes of the liver tissue showed obvious lesion. The success rate of modeling was 90%. Compared with the sham-operation control group， the serum ALT，AST activity， the TNF-α content， and the hepatic COX-2 protein expression markedly increased in the CLP group （P<0.01）. Polydatin improved the sepsis-induced mortality dose-dependently， inhibited increased ALT，AST activity and TNF-α， decreased the hepatic COX-2 protein expression， and attenuated the pathological injury of the liver （P<0.05）. Conclusion Polydatin could effectively protect sepsis-induced ALI， which might be achieved possibly through inhibiting serum TNF-α production and hepatic COX-2 expression.

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