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丹芍化纤对大鼠肝纤维化中PPAR-γ和NF-κB表达的影响

Effects of Dan-shao-hua-xian on expression of PPAR-gamma and NF-kappa B in rat liver fibrosis.

作者信息

Wang He-Yan, Cheng Ming-Liang

机构信息

Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2008 Apr;7(2):179-84.

Abstract

BACKGROUND

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and nuclear factor kappa B (NF-kappaB) play important roles in liver fibrosis. This study aimed to investigate the effects of Dan-shao-hua-xian, a preparation of traditional Chinese medicine, on the expression of PPAR-gamma and NF-kappaB in the fibrotic livers of rats.

METHODS

Seventy Wistar rats were randomly divided into 4 groups: treatment (model, 8 weeks+treatment, 8 weeks; group A), natural recovery ( model, 8 weeks+saline, 8 weeks; group B), model (model only, 8 weeks; group C), and control (normal, untreated, 16 weeks; group D). Each group consisted of 20 rats (except for group D, which had 10). Fibrotic liver models were induced in rats by subcutaneous injection of CCl4, oral administration of alcohol and a high-lipid/low-protein diet for 8 weeks. After the models were established, the rats in group A were orally given Dan-shao-hua-xian capsules daily for another 8 weeks. Then, the liver indices serum hyaluronic acid (HA), tumor necrosis factor-alpha (TNF-alpha) and alanine aminotransferase (ALT) were measured. The degree of hepatic fibrosis was evaluated by optical microscopy. Hydroxyproline (Hyp) in the liver tissue was determined. The expression of PPAR-gamma was detected by immunohistochemical techniques. The protein levels of PPAR-gamma and NF-kappaB were determined by Western blotting.

RESULTS

The concentrations of serum HA, TNF-alpha and Hyp in group C increased compared with group D (P<0.05), and they decreased in group A compared with group C (P<0.05). The expression of PPAR-gamma in group C decreased compared with group D (P<0.05), and it increased in group A compared with groups B and C (P<0.05). Similarly, Western blotting showed that the expression of PPAR-gamma in group C decreased compared with group D, and it increased in group A compared with group C. The expression of NF-kappaB increased in group C compared with group D (P<0.05), and it decreased in group A compared with group C (P<0.05).

CONCLUSION

Dan-shao-hua-xian capsules enhance the expression of PPAR-gamma but decrease that of TNF-alpha and NF-kappaB in the liver tissues of CCl4-induced hepatic fibrotic rats. These effects may play a role in its activity in treating hepatic fibrosis.

摘要

背景

过氧化物酶体增殖物激活受体γ(PPAR-γ)和核因子κB(NF-κB)在肝纤维化中起重要作用。本研究旨在探讨中药制剂丹芍化纤对大鼠肝纤维化组织中PPAR-γ和NF-κB表达的影响。

方法

将70只Wistar大鼠随机分为4组:治疗组(造模8周+治疗8周;A组)、自然恢复组(造模8周+生理盐水8周;B组)、模型组(仅造模8周;C组)和对照组(正常未处理16周;D组)。每组20只大鼠(D组10只)。通过皮下注射四氯化碳、灌胃酒精及高脂低蛋白饮食8周诱导大鼠肝纤维化模型。模型建立后,A组大鼠每日口服丹芍化纤胶囊,持续8周。然后,检测肝指标血清透明质酸(HA)、肿瘤坏死因子-α(TNF-α)和丙氨酸转氨酶(ALT)。通过光学显微镜评估肝纤维化程度。测定肝组织中羟脯氨酸(Hyp)含量。采用免疫组织化学技术检测PPAR-γ的表达。通过蛋白质印迹法测定PPAR-γ和NF-κB的蛋白水平。

结果

与D组相比,C组血清HA、TNF-α和Hyp浓度升高(P<0.05),与C组相比,A组降低(P<0.05)。与D组相比,C组PPAR-γ表达降低(P<0.05),与B组和C组相比,A组升高(P<0.05)。同样,蛋白质印迹法显示,与D组相比,C组PPAR-γ表达降低,与C组相比,A组升高。与D组相比,C组NF-κB表达升高(P<0.05),与C组相比,A组降低(P<0.05)。

结论

丹芍化纤胶囊可增强四氯化碳诱导的肝纤维化大鼠肝组织中PPAR-γ的表达,但降低TNF-α和NF-κB的表达。这些作用可能在其治疗肝纤维化的活性中发挥作用。

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