| Objective:To search for the suitable model to the therapeutical principle and method under the guidenece of TCM theory. Observe the liver protection respectively by two different methods for curting deterioration of damp-heat syndrome, and explore the action mechanism. To study specially the the effect of prescription on oncosis, and investigate the action mechanism of liver protection. Hope that it can provide more new theoretical basis and effective prescriptions for treatment of acute liver injury.Methods:Choose suitable prescriptions and model according chinese medicine syndrome types to study the curative effect and action mechanism. Select the prescription of Chaihu Yugan Detection that helps to clear heat, dispel dampness, promote blood flow, nourish yin targeting at predominance of heat, to remedy acute liver injury rats caused by D-Gal rats with acute liver injury.And select the chinese herb of radix aconiti carmichaeli that helps to warming yang,dipel cold,and relieve the pain to remedy acute liver injury rats that caused by BCG/LPS.To investigate the curative effection and action mechanism.1.Chaihu Yugan Detection remedy the acute liver injury caused by D-Galn:Sixty female SD rats were randomized into six groups with 10 in each group, normal control group, model group, diphenyl dimethyl bicarboxylate (DDB) group, low-dose group, middle-dose group and high-dose group. Intraperitoneal injection of D-Galn at a dose of 600mg/kg was administered to the rats except those in the normal control group to induce acute liver injury. Medications were given orally to each treatment group at the same time, of which the daily dose of DDB is 4.5mg/kg, and dosage of the three herbal groups was 11.8g/kg,23.6g/kg and 47g/kg respectively,2 daily. All the medications were given at a volume of 10ml/kg, twice a day for two days.48 hours later, all the rats were sacrificed with their serum ALT, AST, TB, Calpain, TNF- ?and IL-18 being examined. Right lobe of the liver was applied to make routine HE slices and pathological changes were examined under the microscope. The expression of bcl-2 and bax were analyzed by immunohistochemical.2. Radix aconiti carmichaeli remedy the acute liver injury caused by BCG/LPS: Divide 50 rats into 5 groups randomly:normal control group(group A), model group (group B), low-dose group (group C), middle-dose group (group D) and high-dose group (group E). BCG and LPS were injected intrapefitoneally(ip) to rats in Gb?Gc?Gd and Ge to induce acute immune liver injury. And then Gc?Gd and Ge were treated with different doses of traditional Chinese medicine respective. Observe the changes of ALT?AST?TBIL?MDA?SOD in serum of rats and the diseased tissues. Verify the smaller molecule metabolites in liver tissue by nuclear magnetic resonance.Results:1. The curative effect of Chaihu Yugan Decoction on acute liver injury caused by D-Galn:(1)The Chaihu Yugan Decoction at an oral dose of 11.8g/kg and 47g/kg exhibited a significant (P<0.05 for all) curative effect by normalizing the levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and total bilirubin (TB) which were significantly (P<0.05) increased at 48h later in rats by treatment with 600 mg/kg D-Galn. DDB (4.5 mg/kg), a known hepatoprotective drug used for comparison exhibited significant curative effect in terms of ALT, AST and TB (P<0.05). The Chaihu Yugan Decoction at an oral dose of 23.6g/kg exhibited significant curative effect in terms of ALT and TB (P<0.05).(2) Calpain?Tumor necrosis factor alpha (TNF-?) and interleukin-18(IL-18) levels in human plusma increased significantly in the model group compared to that of normal group (P<0.05). DDB group and low dose group exhibited a significant (P<0.05 for all) curative effect by normalizing the levels of Calpain?TNF-?and IL-18 compared to model group.(3) The expression of bax levels decreased significantly, whereas bcl-2 increased significantly in the model group compared to that of normal group (P<0.05). DDB group, low dose group and high dose group exhibited a significant (P<0.05 for all) curative effect by normalizing the levels of bax and increasing the levels of bcl-2 compared to modle group. Middle dose group did not affect bcl-2 or bax levels in liver tissue significantly (P> 0.05)(4)Pathologic changes from the HE slices suggested that size of fatty degeneration, hydropic degeneration and focal necrosis in the model group was much larger than that of the treatment group in which the high dose group and DDB group exhibited the better protective effects.(5) The ultrastructure of the hepatocyte showed that:liver cells in model group appeared simultaneous death of oncosis and apoptosis. There were swollen nad deformed mitochondrias in liver cells, some of which were destroyed in structure. Endoplasmic reticulum expanded or collapsed. High dose group and DDB group exhibited the better protective effect. Middle dose group was not significantly difference than modle group.2. Curative effect and metabonomic of radix aconiti carmichaeli to acute liver injury caused by BCG/LPS:(1)All the treatment groups exhibited a significant (P<0.01 for all) curative effect by normalizing the levels of alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin (TB) and MDA which were significantly (P<0.05) increased in rats by treatment with BCG/LPS.(2) Pathologic changes from the HE slices suggested that size of lobular architecture were almost normal in all treatment groups. Hydropic degeneration and focal necrosis in treatment groups was much larger than that of the treatment group in which the high dose group and DDB group exhibited the better protective effectsConclusions:1. Chaihu Yugan Decoction could lower down the increased serum ALT, AST and TB levels in D-Galn-induced hepatotoxic rats and decrease the size of degeneration and necrosis in the liver due to D-Galn hepatotoxicity which indicates its prominent curative effect. The antagonism of Chaihu Yugan Decoction on necrosis may be correlated with an increase Bcl-2 and a decrease expression of Bax,Calpain and TNF-?.2. Radix aconiti carmichaeli can abate the liver injury in immune liver injury model rats and and possess a certain action of protecting liver and lowering transaminase. To use metabolomic method to help evaluate drug efficacy is a direct, comprehensive, and effective new method.3. Two different treatment methods Targeting at heat and dampness, cold and dampness both exhibited varying degree curative effect. |
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