摘要
目的:研究穿心莲内酯(AP)对小鼠急性四氯化碳(CCl4)肝损伤的保护作用及其机制。方法:40只小鼠随机分成5组,正常对照组、肝损伤模型组、AP低剂量组(50 mg/kg)、高剂量组(100 mg/kg)和阳性药物组。分别测定小鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)含量;肝匀浆中丙二醛(MDA)、还原型谷胱甘肽(GSH)的含量及肝组织病理学变化;逆转录PCR(RT-PCR)检测小鼠肝脏中肿瘤坏死因子α(TNF-α)、血红素加氧酶-1(HO-1)mRNA水平。结果:AP高剂量组(100 mg/kg)降低小鼠血清中ALT、AST水平,提高肝组织中GSH活性,降低MDA水平,差异均有统计学意义(P<0.05);病理镜检显示AP高剂量组明显减轻肝损伤;RT-PCR结果显示,AP高剂量组TNF-α表达水平降低,而HO-1表达增强,差异均有统计学意义(P<0.05)。结论:AP通过抑制脂质过氧化反应,降低组织中氧自由基的生成保护急性四氯化碳肝损伤,其机制可能与抑制TNF-α的表达,诱导HO-1表达有关。
Objective To investigate the role of andrographolide （AP） in protection of carbon tetrachloride （CCl4）-induced acute liver injury in mice and the possible mechanisms. Methods The mice were randomly divided into five groups, including two groups with different doses of AP （50 mg/kg and100 mg/kg）, a control group, a CCl4 model group, and a silymarin group. Serum levels of alanine aminotransferase （ALT）, aspartateminotransferase （AST）, hepatic malondialdehyde （MDA）, and glutathione （GSH） were examined. Pathological changes in the liver were observed. RT-PCR was used to detect the expressions of tumor necrosis factor-a （TNF-α） and heme oxygenase-1 （HO-1） mRNA. Results As compared with CCl4 model group, serum levels of ALT and AST and hepatic MDA activity were significantly decreased in AP group （100 mg＆#183;kg-1）, along with a remarkable increase in hepatic GSH content. Pretreatment with AP at a high dose alleviated histopathological changes induced by CCl4. A markedly increased level of TNF-a induced by CCl4 was reduced by AP, while HO-1at transcriptional level was dramatically elevated following AP pretreatment. Conclusions AP plays a role in protection of CCl4-induced acute liver injury by inhibiting lipid peroxidation and reducing formation of free radicals, the mechanism may be involved in inhibition of TNF-αand activation of HO-1.
出处
《实用医学杂志》
CAS
北大核心
2014年第14期2204-2207,共4页
The Journal of Practical Medicine
基金
南方医科大学公共卫生与热带医学学院院长基金(编号:GW201225)
关键词
穿心莲内酯
四氯化碳
肝损伤
Andrographolide
Carbon tetrachloride
Liver injury
