茶多酚抑制大鼠诱导型一氧化氮合酶和肿瘤坏死因子-α的表达，并预防脂多糖诱导的肝损伤。

Tea polyphenols inhibit expressions of iNOS and TNF-alpha and prevent lipopolysaccharide-induced liver injury in rats.

作者信息

Yuan Guang-Jin, Gong Zuo-Jiong, Sun Xiao-Mei, Zheng Shi-Hua, Li Xi

机构信息

Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2006 May;5(2):262-7.

PMID:16698588

Abstract

BACKGROUND

Tea polyphenols have been shown to protect against carbon tetrachloride (CCl4)-induced liver injury, liver fibrosis, hepatic ischemia-reperfusion injury. In this study, we examined the effect of tea polyphenols on lipopolysaccharide (LPS)-induced liver injury, and explored its mechanisms.

METHODS

Sprague-Dawley rats received tea polyphenols (100 mg.kg-1.d-1) or vehicle (water) intragastrically by gavage for 14 days, followed by LPS (5 mg/kg) or saline injection intraperitoneally. Liver injury was assessed by biochemical assay and pathological analysis. Serum tumor necrosis factor-alpha (TNF-alpha) levels and liver malondialdehyde (MDA) contents were determined. Inducible nitric oxide synthase (iNOS) protein and TNF-alpha, iNOS and endothelial nitric oxide synthase (eNOS) mRNA expressions in the liver were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively.

RESULTS

Administration of LPS resulted in liver injury in rats, evidenced by elevated activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatocellular necrosis, and neutrophil infiltration in the liver. These responses were associated with increased serum TNF-alpha levels, induced iNOS protein, expressions of TNF-alpha, iNOS mRNA in the liver and elevated lipid peroxidation at 90 minutes or 6 hours after LPS injection. Pretreatment with tea polyphenols attenuated LPS-induced liver injury, and blunted the rises of serum TNF-alpha levels and lipid peroxidation and the induction of expressions of TNF-alpha, iNOS in the liver.

CONCLUSION

Tea polyphenols prevent LPS-induced liver injury, and the mechanisms may involve the reduction of serum TNF-alpha levels and lipid peroxidation and the suppression of TNF-alpha, iNOS expressions in the liver.

摘要

背景

茶多酚已被证明可预防四氯化碳（CCl4）诱导的肝损伤、肝纤维化、肝缺血再灌注损伤。在本研究中，我们检测了茶多酚对脂多糖（LPS）诱导的肝损伤的影响，并探讨其机制。

方法

将Sprague-Dawley大鼠通过灌胃给予茶多酚（100mg·kg-1·d-1）或溶剂（水），持续14天，随后腹腔注射LPS（5mg/kg）或生理盐水。通过生化分析和病理分析评估肝损伤。测定血清肿瘤坏死因子-α（TNF-α）水平和肝脏丙二醛（MDA）含量。分别通过免疫组织化学和逆转录聚合酶链反应（RT-PCR）检测肝脏中诱导型一氧化氮合酶（iNOS）蛋白以及TNF-α、iNOS和内皮型一氧化氮合酶（eNOS）mRNA的表达。

结果

给予LPS导致大鼠肝损伤，表现为血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性升高、肝细胞坏死以及肝脏中性粒细胞浸润。这些反应与LPS注射后90分钟或6小时血清TNF-α水平升高、诱导的iNOS蛋白、肝脏中TNF-α和iNOS mRNA的表达以及脂质过氧化增加有关。茶多酚预处理减轻了LPS诱导的肝损伤，并减弱了血清TNF-α水平和脂质过氧化的升高以及肝脏中TNF-α、iNOS表达的诱导。