丹酚酸B盐对大鼠纤维化肝组织脂质过氧化及其MMP-2活性的影响  

Effects of salvianolic acid B on lipid peroxidation and metalloproteinase-2 activity in fibrotic liver in rat

作　　者：王丽娜[1,2] 陶艳艳[1] 李书[1] 陈高峰[1] 刘成海[1,3] 

机构地区：[1]上海中医药大学附属曙光医院肝病研究所,上海201203 [2]第二军医大学附属长海医院中医科,上海200433 [3]上海高校中医内科学E-研究院,上海201203

出　　处：《中国中药杂志》2010年第1期71-75,共5页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(30472047;30772869);上海市科委优秀学科带头人计划项目(08XD14041);上海高校中医内科学E研究院建设项目(E03008);上海市教委创新团队

摘　　要：目的:探讨丹酚酸B盐影响纤维化肝脏脂质过氧化与MMP-2活性的抗肝纤维化作用机制。方法:Wistar大鼠随机分为正常组、模型组、丹酚酸B盐组与培哚普利组。以二甲基亚硝胺腹腔注射复制肝纤维化模型,隔天1次,连续4周。丹酚酸B盐预防组与培哚普利对照组于造模开始即开始灌服,正常组与模型组大鼠给予等量生理盐水,连续4周。HE染色与胶原染色观察肝组织炎性坏死与胶原沉积;试剂盒检测血清肝功能(ALT,AST,Alb,T.Bil)与肝组织SOD活性、GSH含量与GST活性;盐酸水解法测定肝组织Hyp含量,Western blot检测I型胶原和α-SMA蛋白表达。明胶酶谱法检测肝组织MMP-2/9的活性。结果:模型大鼠肝脏有明显胶原沉积与肝纤维化,伴有明显肝细胞炎性损伤坏死;模型大鼠血清T.Bil含量、ALT与AST活性明显升高,血清Alb含量明显减少;肝组织Hyp含量、α-SMA与I型胶原蛋白、MMP-2活性明显增加,GSH含量、SOD与GST活性明显降低。丹酚酸B盐与培哚普利明显减轻肝纤维化模型大鼠的血清ALT水平与肝组织Hyp含量,抑制模型大鼠肝组织的α-SMA与I型胶原蛋白表达,以丹酚酸B盐作用明显,且均下调肝组织MMP-2活性,而增加SOD活性与GSH含量;丹酚酸B盐尚可降低模型大鼠血清T.Bil含量、提高肝组织GST活性。结论:改善纤维化肝脏的脂质过氧化损伤与降低肝组织MMP-2活性是丹酚酸B盐预防肝纤维化重要作用机制。Objective： To investigate the mechanism of salvianolic acid B （ Sal B） action against liver fibrosis through preven- ting lipid peroxidation and regulating MMP-2 activity in liver. Method： The liver fibrotic model was induced through intraperitoneally injection of DMN at a dose of 10 μg . kg-1 for every other day and lasting for 4 weeks. Sal B was administered （10 mg . kg-1 ）, and perindopril （5 mg- kg-1） was used as positive control. Hepatic inflammation and collagen were observed with HE and sirius red staining. The liver function including serum ALT, AST activity, Alb and total bilirubin （T. Bil） level were determined. The hepatic lipid peroxidation including SOD and GST activities and GSH content were measured. Hepatic hydroxyproline （Hyp） content was detected with Jamalls method. The activity of metalloproteinase was assayed by gelatin zymography. The expressions of α-SMA, Col I in liver tissue were analyzed by Western blot. Result： The model rats had higher serum T. Bil content, ALT and AST activities but lower Alb content than the normal rats, also had remarkable inflammatory necrosis and collagen deposition in liver, with much higher Hyp content, protein expression of α-SMA and collagen I and MMP-2 activity in liver, but had a decreased GSH content, SOD and GST activities. Both Sal B and perindopril attenuated hepatic injury and collagen deposition in model rats, decreased serum ALT activity and hepatic Hyp content, down-regulated α-SMA and collagen I protein expressions and metalloproteinase-2 activity than those in the model group, but increased SOD activity and GSH content, and Sal B decreased serum T. Bil content and increased GST activity. Sal B had a much better comprehensive actions than perindopril. Conclusion： Sal B has a good preventive action against liver fibrosis, the action mechanism is related to the prevention from lipid peroxidation and down-regulation of metalloproteinase-2 activity in fibrotic liver.

关 键 词：肝纤维化 丹酚酸B盐 脂质过氧化 基质金属蛋白酶 培哚普利 

分 类 号：R285.5[医药卫生—中药学]