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[清热活血方对四氯化碳诱导小鼠肝纤维化防治作用的比较]

[Comparison of effect of formulas clearing away heat and promoting blood circulation on prevention and treatment of liver fibrosis in CCl4 mice].

作者信息

Zhao Zhimin, Yu Huiying, Peng Yuan, Ren Hongxu, Tao Yanyan, Wang Zhengtao, Zhu Bangxian, Liu Ping, Liu Chenghai

机构信息

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Liver Disease Research Institute of Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2012 Jun;37(12):1804-8.

Abstract

OBJECTIVE

To observe the effect of traditional Chinese medicine formulas clearing away heat and promoting blood circulation-Biejiayinzi (BJYZ), Gexiazhuyu Tang (GXZYT) and Fugan Wan (FGW) on liver fibrosis in CCl4 mice by screening and analyzing formula-syndrome database of kidney and liver fibrosis based on the principle of formula-syndrome, compared with pivot-harmonizing decoction.

METHOD

Ten-week-old male C57BL/6 mice, with the weight of (20 +/- 3) g, were randomly divided into 6 groups: the normal group, the model group, the BJYZ group, the GXZY group, the FGW group and the XST group. Except the normal group, other groups were abdominally injected with 10% CCl4 olive oil solution a dose of 2 mL x kg(-1) body weight for four weeks, three times each week. Meanwhile, the latter four groups were administered with extracts of BJYZ, GXZYT, FGW and XST, respectively, once every day, concomitantly continued CCl4 administration. The normal and the model groups were given the same volume of deionized water. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (gamma-GT), Alb and TBil were detected by chemiluminescence. The hydroxyproline (HYP) content was detected by acid hydrolysis method. The hepatic collagen deposition was evaluated with Sirius red staining.

RESULT

Compared with the normal group, the model group recorded notable decrease in weight and increase in the ratio of liver weight and body weight and the ratio of spleen weight and body weight, with obvious fatty degeneration and inflammatory necrosis in liver cells. Collagen fiber deposition was so notable to form fibrous septums and pseudolobules. The levels of serum ALT, AST, TBil, gamma-GT, the HYP content in liver tissue and the deposition of hepatic collagen were significantly increased in the model group. Compared with model group, Serum AST were significantly decreased in BJYZ group as gamma-GT decreased in the GXZYT group, without notable decrease in degeneration and inflammatory necrosis in liver cells and collagen deposition. The GXZYT group showed significant decrease in gamma-GT, with slight improvement in degeneration and inflammatory necrosis in liver cells and reduction in collagen deposition. The ratio of liver weight and body weight, AST, gamma-GT and HYP content were significantly decreased in the FGW group, with slight improvement in degeneration and inflammatory necrosis in liver cells and reduction in collagen deposition. The XST group showed decrease in the ratio of liver weight and body weight, with no obvious change in inflammation and fibrosis of hepatic tissue.

CONCLUSION

FGW shows the best effect of prevention and treatment of liver fibrosis in CCl4 mice.

摘要

目的

基于方证原理筛选分析肝肾纤维化方证数据库,观察清热活血类中药方剂鳖甲饮子(BJYZ)、膈下逐瘀汤(GXZYT)和复肝丸(FGW)对四氯化碳(CCl4)致小鼠肝纤维化的影响,并与枢和汤作对照。

方法

选取10周龄雄性C57BL/6小鼠,体重(20±3)g,随机分为6组:正常组、模型组、BJYZ组、GXZY组、FGW组和XST组。除正常组外,其余各组小鼠腹腔注射10% CCl4橄榄油溶液,剂量为2 mL·kg-1体重,每周3次,共4周。同时,后4组分别给予BJYZ、GXZYT、FGW和XST提取物,每日1次,同时继续给予CCl4。正常组和模型组给予等体积去离子水。采用化学发光法检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(γ-GT)、白蛋白(Alb)和总胆红素(TBil)水平。采用酸水解法检测羟脯氨酸(HYP)含量。用天狼星红染色法评估肝脏胶原沉积。

结果

与正常组相比,模型组小鼠体重显著下降,肝重与体重比值、脾重与体重比值升高,肝细胞出现明显脂肪变性和炎性坏死。胶原纤维沉积显著,形成纤维间隔和假小叶。模型组血清ALT、AST、TBil、γ-GT水平、肝组织HYP含量及肝脏胶原沉积均显著增加。与模型组相比,BJYZ组血清AST显著降低,GXZYT组γ-GT降低,但肝细胞变性和炎性坏死及胶原沉积无明显减轻。GXZYT组γ-GT显著降低,肝细胞变性和炎性坏死略有改善,胶原沉积减少。FGW组肝重与体重比值、AST、γ-GT及HYP含量显著降低,肝细胞变性和炎性坏死略有改善,胶原沉积减少。XST组肝重与体重比值降低,肝组织炎症和纤维化无明显变化。

结论

FGW对CCl4致小鼠肝纤维化的防治效果最佳。

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