Wang Lina, Tao Yanyan, Li Shu, Chen Gaofeng, Liu Chenghai
Liver Disease Institute, Shanghai University of Traditional Chinese Medicine, Shuguang Hospital, Shanghai 201203, China.
Zhongguo Zhong Yao Za Zhi. 2010 Jan;35(1):71-5.
To investigate the mechanism of salvianolic acid B (Sal B) action against liver fibrosis through preventing lipid peroxidation and regulating MMP-2 activity in liver.
The liver fibrotic model was induced through intraperitoneally injection of DMN at a dose of 10 microg x kg(-1) for every other day and lasting for 4 weeks. Sal B was administered (10 mg x kg(-1)), and perindopril (5 mg x 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 Jamall's method. The activity of metalloproteinase was assayed by gelatin zymography. The expressions of alpha-SMA, Col I in liver tissue were analyzed by Western blot.
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 alpha-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 alpha-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.
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.
通过预防脂质过氧化和调节肝脏中基质金属蛋白酶-2（MMP-2）的活性，探讨丹酚酸B（Sal B）抗肝纤维化的作用机制。
通过每隔一天腹腔注射10μg·kg⁻¹的DMN诱导肝纤维化模型，持续4周。给予Sal B（10mg·kg⁻¹），培哚普利（5mg·kg⁻¹）作为阳性对照。采用HE和天狼星红染色观察肝脏炎症和胶原情况。测定肝功能，包括血清谷丙转氨酶（ALT）、谷草转氨酶（AST）活性、白蛋白（Alb）和总胆红素（T. Bil）水平。检测肝脏脂质过氧化，包括超氧化物歧化酶（SOD）和谷胱甘肽S-转移酶（GST）活性以及谷胱甘肽（GSH）含量。采用Jamall法检测肝脏羟脯氨酸（Hyp）含量。通过明胶酶谱法测定金属蛋白酶的活性。采用蛋白质免疫印迹法分析肝脏组织中α-平滑肌肌动蛋白（α-SMA）、I型胶原（Col I）的表达。
模型大鼠血清T. Bil含量、ALT和AST活性高于正常大鼠，Alb含量低于正常大鼠，肝脏有明显的炎症坏死和胶原沉积，肝脏Hyp含量、α-SMA和I型胶原的蛋白表达以及MMP-2活性均显著升高，但GSH含量、SOD和GST活性降低。Sal B和培哚普利均可减轻模型大鼠的肝损伤和胶原沉积，降低血清ALT活性和肝脏Hyp含量，下调α-SMA和I型胶原蛋白表达以及金属蛋白酶-2活性，高于模型组，但增加SOD活性和GSH含量，且Sal B降低血清T. Bil含量并增加GST活性。Sal B的综合作用优于培哚普利。
Sal B对肝纤维化具有良好的预防作用，其作用机制与预防脂质过氧化和下调纤维化肝脏中金属蛋白酶-2的活性有关。
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