当归补血汤对肝纤维化大鼠脂质过氧化及 MMP-2/9 活性的影响。
Effects of Danggui Buxue Decoction () on lipid peroxidation and MMP-2/9 activities of fibrotic liver in rats.
机构信息
Shuguang Hospital, Liver Disease Institute, Shanghai University of Traditional Chinese Medicine, China.
出版信息
Chin J Integr Med. 2009 Dec;15(6):435-41. doi: 10.1007/s11655-009-0435-y. Epub 2010 Jan 18.
OBJECTIVE
To explore the mechanism of Danggui Buxue Decoction (, DBD) on the liver fifibrosis related to hepatic lipid peroxidation and matrix metalloproteinases (MMP) -2/9 activities.
METHODS
The liver fifibrosis in 28 rats was induced by an injection of carbon tetrachloride (CCl(4)) and fed with high lipid and low protein diet for 6 weeks, the model rats were randomly divided into the model group and DBD treated group, 14 in each group, and another 10 rats as the normal group were observed as well. Rats in the DBD group were administered with DBD at the dose of 6 g/kg body weight for 6 weeks since CCl(4) intoxication. The hepatic inflammation and fibrosis were examined with HE and Sirius red stain. The liver function including serum alanine aminotransamine (ALT), aspartate transamine (AST), albumin (Alb) and total bilirubin (TBIL), liver triglyceride (TG) and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity were assayed. Hepatic hydroxyproline (Hyp) content was detected with Jamall's method. The alpha-SMA expression was analyzed by immunohistochemistry and the Western blot. Liver MMP-2 mRNA was analyzed with Real-time PCR, and MMP-2/9 activities were measured with gelatin zymography and in situ zymography.
RESULTS
Compared with the normal group, the levels of ALT, AST and TBIL, the content of Hyp, TG and MDA were remarkably increased, the Alb content and SOD activity were signifificantly decreased in the model group (P<0.05), and higher levels of MMP-2 mRNA and MMP-2/9 activities (P<0.01), the hepatic fatty degeneration and collagen accumulation and fifibrosis at liver were observed. Compared with the model control, DBD group showed slighter hepatic fatty degeneration and collagen deposition, and had lower levels of ALT, AST and TBIL activities, lower contents of MDA, TG and Hyp, but higher SOD level and Alb content (P<0.05), and DBD also down-regulated MMP-2 mRNA expression and decreased MMP-2/9 activities in the fifibrotic livers (P<0.01).
CONCLUSION
The action of DBD against liver fibrosis is related to prevent lipid peroxidation and inhibit MMP-2/9 activities in the fibrotic livers.
目的
探讨当归补血汤（DBD）通过抑制肝脂质过氧化和基质金属蛋白酶（MMP）-2/9 的活性来治疗肝纤维化的机制。
方法
28 只大鼠通过注射四氯化碳（CCl4）和高脂低蛋白饮食喂养 6 周诱导肝纤维化，将模型大鼠随机分为模型组和 DBD 治疗组，每组 14 只，另设 10 只大鼠作为正常组。DBD 治疗组大鼠在 CCl4 中毒后给予 6g/kg 体重的 DBD 治疗 6 周。采用 HE 和天狼猩红染色法观察肝组织炎症和纤维化情况。检测血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、白蛋白（Alb）和总胆红素（TBIL）、肝甘油三酯（TG）和丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性，采用贾马法检测肝羟脯氨酸（Hyp）含量。免疫组化法分析α-SMA 表达，Western blot 法分析肝 MMP-2 蛋白表达。采用实时 PCR 法分析肝 MMP-2mRNA 表达，明胶酶谱法和原位酶谱法检测 MMP-2/9 活性。
结果
与正常组比较，模型组 ALT、AST 和 TBIL 水平、Hyp、TG 和 MDA 含量显著升高，Alb 含量和 SOD 活性显著降低（P<0.05），MMP-2mRNA 水平和 MMP-2/9 活性显著升高（P<0.01），肝组织脂肪变性和胶原堆积及纤维化明显。与模型对照组比较，DBD 组肝组织脂肪变性和胶原沉积程度较轻，ALT、AST 和 TBIL 活性较低，MDA、TG 和 Hyp 含量较低，SOD 水平和 Alb 含量较高（P<0.05），DBD 还可下调肝纤维化组织中 MMP-2mRNA 表达，降低 MMP-2/9 活性（P<0.01）。
结论
DBD 抗肝纤维化的作用与其预防肝纤维化组织脂质过氧化和抑制 MMP-2/9 活性有关。
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