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黄连素对高脂饮食肝损伤大鼠肝中NO合成酶及凋亡相关基因的干预与调控

Modulation of Berberine on the Expression of Nitric Oxide Synthase and Bax, Bcl-2 in Liver Injury Mice Treated by High Fat-High Cholesterol Diet

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【作者】 王黎马瑶付婷婷刘颖王莹周娟高天芸洪蓓蓓孙玉芹丁虹

【Author】 Wang li, Ma Yao, Fu Tingting, Liu Ying, Wang Ying, Zhou Juan, Gao Tianyun, Hong Beibei, Sun Yuqin, Ding Hong(College of Pharmacy, Wuhan University, Wuhan 430072,P. R. China)

【机构】 武汉大学药学院武汉大学药学院 武汉 430072武汉 430072

【摘要】 目的:研究高脂饮食肝损伤中结构型(cNOS)、诱导型(iNOS)一氧化氮(NO)合成酶及凋亡相关基因Bax、Bcl-2表达的变化,在进一步探讨脂肪性肝损伤机制的同时观察黄连素的干预调控作用。方法:建立高脂饮食大鼠肝损伤模型,ig给予黄连素20,40,60 mg·kg-1,测定血中TC,TG,HDL,LDL含量及ALT,GST活性和肝中NO含量;免疫组化方法观察cNOS,iN- OS,Bax,Bcl-2的表达。结果:黄连素可使血中TC,TG,LDL含量及sALT,sGST活性下降,呈良好的剂量依赖关系,对HDL无明显作用;能显著抑制肝组织中NO的生成;黄连素对高脂饮食大鼠肝组织中iNOS,Bax表达有一定的抑制作用,但作用无显著性差异;可显著上调肝组织中cNOS及Bcl-2的表达,但不呈剂量依赖关系。结论:黄连素可保护南脂饮食所致的肝损伤,可显著上调抗凋亡基因Bcl-2的表达,提示黄连素可能通过抗肝细胞凋亡保护高脂饮食引起的肝细胞损伤。

【Abstract】 Objective: To investigate the modulation of Berberine on the expression of nitric oxide synthase and Bax, Bcl-2 in liver injury mice treated by high fat-high cholesterol diet. Method: Liver injury model was induced by high-fat-high-cholesterol. Berberine was administrated to mice with 20, 40, 60 mg·kg-1 , respectively, ig, once a day. Mice were sacrificed at the end of the 6th week, the effects of Berberine on the expression of inducible, constitutive nitric oxide synthase and Bax, Bcl-2 gene were assessed by immuno his to chemistry , and the nitric oxide (NO) production, alanine transaminase(sALT) activity,glutathione S-transferase(sGST) activity in serum were determined. Result: Compared with the normal mice, the NO production,TC、TG、LDL content and sALT, sGST level were increased significantly, no change of HDL was found; iNOS, Bax expression were up-regulation, cNOS expression and Bcl-2 expression were down-regulation in liver injury mice. The Berberine could obviously reduce NO production and sALT, sGST level, increase the expression of cNOS and Bcl-2, and no effect on iNOS, Bax expression was found. Conclusion: Berberine can alleviate the liver injury by modulation of the expression of cNOS, Bcl-2 to prevent apoptosis.

【基金】 国家973重大基础研究专项(2002ccc00300)
  • 【文献出处】 中国药师 ,China Pharmacist , 编辑部邮箱 ,2006年05期
  • 【分类号】R285.5
  • 【被引频次】20
  • 【下载频次】204
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