丹酚酸B抑制CCl_4诱导大鼠肝纤维化形成的基因表达谱分析  

Gene Expression Profile Analysis of Salvianolic Acid B in Inhibiting Formation of CCl_4-induced Rat Liver Fibrosis

作　　者：王晓玲[1] 刘平[2] 胡旭东[1] 应馨萍[3] 李伯勤[3] 

机构地区：[1]上海中医药大学生物教研室,上海201203 [2]上海中医药大学肝病研究所,上海201203 [3]上海中医药大学教学实验中心,上海201203

出　　处：《上海中医药大学学报》2007年第2期50-53,共4页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金青年基金资助项目(30000230)

摘　　要：目的:利用基因芯片技术,通过分析基因表达谱的变化,从基因表达的整体水平上探讨丹酚酸B抗肝纤维化的作用机制。方法:采用40%CCl4—橄榄油皮下注射20周制备大鼠肝纤维化模型。分为正常对照组、模型组、丹酚酸B低剂量组(9.38mg/kg体重),丹酚酸B高剂量组(18.75mg/kg体重)和秋水仙碱阳性对照组。第9周开始给予各组相应的药物,正常对照组、模型组给予等量的生理盐水。检测大鼠肝组织羟脯氨酸(HyP)、丙二醛(MDA)、超氧化物歧化酶(SOD),及血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、白蛋白(ALb)。采用小鼠cDNA芯片分析肝组织基因表达谱的变化。结果:丹酚酸B可显著降低血清ALT及AST活性和升高ALb含量,降低肝脏HyP、MDA含量和升高SOD活性,且低剂量组效果优于高剂量组。丹酚酸B可减少CCl4所上调的I、Ⅲ型胶原、SMα-actin、ADP-核糖基化因子-4等基因表达;增加CCl4所下调的ALb、羟基类固醇磺基转移酶和17-β羟基甾醇脱氢酶2型、载脂蛋白C-Ⅲ、调钙蛋白结合蛋白-1、脂肪酸结合蛋白-1、促性腺素调节的长链酰基-CoA合成酶、蛋白磷酸酶-2、TCAM-1等基因表达。结论:丹酚酸B可通过抗脂质过氧化、纠正类固醇和脂肪代谢的紊乱、抑制细胞过度增生、改变细胞间的病理性黏附等多方面的作用,达到抑制肝纤维化形成的效果。Objective:To investigate the mechanism of salvianolic acid B (SAB) on anti-liver fibrosis by analyzing the difference of gene expression profile by cDNA microarray technique. Methods:Liver fibrosis was induced in rats by subcutaneous injection of 40% carbon tetrachloride oily solution for twenty weeks. Animals were divided into five groups,including normal,model, SAB low dose (9.38 mg/kg body weight), SAB high dose (18.75mg/1000g body weight) and colchine groups. SABs and colchine were administered from the ninth week. Liver function was detected by assessing serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, liver tissue hydroxyproline (Hyp) and malondiadehyde (MDA) contents. Superoxide dismutase (SOD) activity, albumin(Alb). The gene expression profile in liver tissues was detected by mice cDNA microarray. Results:SAB significantly reduced the ALT,AST activity and increased the amount of Alb in serum; SAB also significantly reduced the amount of HyP,MDA and enhanced SOD activity in liver tissues. The effect of low dose is better than high dose. SAB reduced the gene expression of pro alpha 1 collagen type Ⅲ, procollagen type I alpha 2,smooth muscle alpha-actin, ADP-ribosylation factor 4 which were up-regulated by CCl4; and SAB increased the gene expression of alpha albumin, hydroxysteroid sulfotransferase,17-beta hydroxysteroid dehydrogenase type 2, apolipoprotein C-Ⅲ,caldesmon 1,fatty acid binding protein 1, gonadotropin-regulated long chain acyl-CoA synthetase, PDZ domain containing 1,protein phosphatase 2,N-acetyltransferase Camello 4, testicular cell adhesion molecule 1 which were down-regulated by CCl4. Conclusion:SAB inhibits CCl4-induced rat liver fibrosis by anti-lipid peroxidation, redresses metabolism derangement of steroids and fatty acids,inhibits over-proliferation of HSC,ameliorates pathology adhesion between cells.

关 键 词：丹酚酸B 肝纤维化 基因芯片技术 

分 类 号：R285[医药卫生—中药学]