基于以方测证的四氯化碳所致大鼠肝纤维化模型的证型探讨

作者	单位
陶庆	上海中医药大学附属曙光医院
孙明瑜	上海中医药大学附属曙光医院
冯琴	上海中医药大学附属曙光医院
彭景华	上海中医药大学附属曙光医院
刘成	上海中医药大学附属曙光医院
胡义扬	上海中医药大学肝肾疾病病证教育部重点研究室
刘平	上海市高校中医内科学E-研究院

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中文摘要:

目的在既往发现一贯煎和下瘀血汤对四氯化碳(CCl4)诱导的大鼠肝纤维化和肝硬化模型有显著效应,并从以方测证角度提出该模型可能以"肝阴虚损、瘀血阻络"表现为特征基础上,进一步进行论证。方法采用皮下注射CCl412周诱导的大鼠慢性肝损伤模型,以功效相近的六味地黄丸以及功效不同的茵陈蒿汤作为参比对象,与已证实有抗肝损伤肝纤维化作用一贯煎进行同步治疗观察。在造模第9周起,随机分模型组、一贯煎组、六味地黄丸组和茵陈蒿汤组,灌胃给药4周。观察大鼠肝功能、肝组织羟脯氨酸(Hyp)及肝组织病理变化。实时定量PCR法观察肝组织α白蛋白(Afamin)、α平滑肌肌动蛋白(α-SMA)mRNA表达变化。结果模型组出现显著的肝损伤和肝纤维化,较之正常组,肝组织Hyp含量显著升高,肝功能显著异常。肝组织Afamin mRNA表达显著降低,α-SMA mRNA表达显著升高。一贯煎可显著降低肝组织Hyp含量及肝脏胶原增生程度(P<0.05),改善肝功能;而六味地黄丸组肝组织Hyp有降低趋势(P=0.09),并显著降低丙氨酸氨基转移酶(ALT)活性,两方均可提高Afamin mRNA表达,降低α-SM AmRNA表达(P<0.05,P<0.01);茵陈蒿汤则无相关药效学效应。结论六味地黄丸和一贯煎的干预效应有一定的"趋同性",支持CCl4所致大鼠慢性肝损伤证属"阴虚"的推测。

英文摘要:

Objective To further demonstrate the cognition upon the prominent effect of Yiguanjian and Xiayuxue Decoction on the CCl4 induced rat model of chronic liver fibrosis which have been verified in the previous studies.From the viewpoint of detecting TCM syndrome by recipe used,through this cognition the pathological features of the liver injury model manifesting a syndrome of "Gan-yin deficiency with blood stasis obstructing collaterals" were further explored.MethodsWistar rats were randomly divided into the normal group,the model group,and the three medicated groups.All rats,except those in the normal group,were made into chronic liver injury model by subcutaneously injecting CCl4 for 12 weeks.Medication for the three medicated groups began from the 9th week after modeling,with oral administering of Yiguanjian(YGJ,a recipe has been verified to be effective for liver injury and fibrosis),Liuwei Dihuang Decoction(LWDH,a recipe with effects similar to YGJ)and Yinchenhao Decoction(YCHD,a recipe functioned differently)respectively for four weeks.Rats were sacrificed at the end of the experiment,changes of hepatic function,liver pathology and hydroxyproline(Hyp)content in the liver tissue were detected,and contents of Afamin and mRNA expression of α-smooth muscle actin(α-SMA)in the liver tissue were assayed as well with Real-time PCR.ResultsAs compared with the normal group,the pathological figures of the chronic liver injury and fibrosis and hepatic function deterioration obviously appeared in the model rats,with the liver content of Hyp and α-SMA mRNA expression increased,and Afamin mRNA expression decreased significantly.In the YGJ treated group,the hepatic collagen hyperplasia and deteriorated hepatic function alleviated significantly after treatment,with content of Hyp significantly lowered,and mRNA expressions of α-SMA and Afamin restored to some extent(P<0.05);the same effects on mRNA expressions of α-SMA and Afamin were shown in the LWDH treated group,also a decreasing trend of Hyp content(0.05<P<0.1),and a significant decreasing of alanine transaminase(ALT)activity was found;while in the YCHD treated group these pharmacological effects mentioned above were not observed at all.ConclusionThe pharmacological effects of LWDH and YGJ were similar to some degree,which gives support to the cognition that the feature of chronic liver injury model rat induced by CCl4 is attributable to yin-deficiency sydrome.

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