Effect Of Lipid - Lowering Disinfectant On Alcoholic Fatty Liver And Intestinal Endotoxemia In Rats And Its Mechanism

Objective:Establishing alcoholic fatty liver combining intestinal en-dotoxemia model on rats. Studying on Jangzhixiaodu decoction’s therape-utic effect, protective effect and partial mechanism on alcoholic fatty liver combining intestinal endotoxemia model on rats.Methods:①Establishing alcoholic fatty liver combining intestinal en-dotoxemia model on rats:The model group and lactulose group rats were fed with15ml·Kg-1·d-1dose of30%,40%,50%of alcohol in turn according to the week, two times a day, and they only drink5%of alcohol. Since the third week the lactulose group rats were fed synchronously with1.35g· Kg-1·d-1dose of lactulose. The the normal group rats were fed with the same dose of physiological saline, the time was7weeks. Since the third weekend, we selected randomly six rats in all group, and observed liver index、serum AST、serum ALT、serum D-LAC、serum DAO、blood plasma LPS and liver pathological morphology.②Jangzhixiaodu decoction’s therapeutic effect, protective effect, relationship of dose and effect on alcoholic fatty liver combining intestinal endotoxemia model on rats:Establishing alcoholic fatty liver combining intestinal endotoxemia model on rats. we intervened in the model by0.5(7.88g·kg-1·d-1),1(15.75g·kg-1·d-1),2(31.5g· kg-1·d-1),4(63g·kg-1·d-1),8(126g·kg-1·d-1) times dose of Jangzhi-xiaodu decoction,0.39g·kg-1·d-1dose of Hugan tablet,1.35g·Kg-1·d-1dose of lactulose in the conditions of interrupting and maintaining alcohol stimulation. And observed liver index, serum AST, serum ALT, liver TG, liver TC, blood plasma LPS and liver pathological morphology.③Mechanism of Jangzhixiaodu decoction’s protective effect:Establishing alcoholic fatty liver combining intestinal endotoxemia model on rats. we intervened in the model by4(63g·kg-1·d-1) times dose of Jangzhixiaodu decoction in the conditions of continued alcohol stimulation. Observation index included serum AST, serum ALT, blood plasma LPS, serum D-LAC, serum DAO, CD14, TLR4, SR gene and protein expression, liver and serum IL-1, IL-6, IL-10, IL-8, TNF-a, IFN-γ.④Jangzhixiaodu decoction’s therapeutic and protect-ive effect on high fat diet induced fatty liver on rats:We intervened in high fat diet induced fatty liver model on rats by15.75g·kg-1·d-1dose of Jangzhixiaodu decoction,0.14g·kg-1·d-1dose of Xuezhikang and0.9mg· kg-1·d-1dose of simvastatinin the the circumstances of interrupting high fat diet and maintaining high fat die. Observation index included liver index, serum AST, serum ALT, liver and serum TG, TC, liver pathol-ogical morphology.Results:②In the fifth week, some indicators on the model group rats met the alcoholic fatty liver. The blood plasma LPS on the model group rats was higher obviously than the normal group rats, blood plasma LPS, intes-tinal permeability and serum AST, serum ALT had consistent performance on the model group rats.②Therapeutic effect and relationship of dose and effect:The indicators on the rats in the Jangzhixiaodu decoction group improved better than the indicators on the rats in the Hugan tablet group and lactulose group, the best therapeutic effect was on the2times group、4times group and8times group rats, in the case of not more than2times of the dose, each indicators improved with increasing the dose. Protective effect and relationship of dose and effect:The indicators on the rats in the Jangzhixiaodu decoction group improved better than the indicators on the rats in the Hugan tablet group and lactulose group, the best protective effect was on the4times group and8times group rats, in the case of not more than8times of the dose, each indicators improved with increasing the dose.③Serum D-LAC and serum DAO’s change were accord ed with blood plasma LPS, serum AST, serum ALT in the model group and4times dose of Jiangzhixiaodu decoction group. IL-1, IL-6, IL-8, TNF-a, IFN-γ in serum and liver, CD14, TLR4gene and protein expression, were accorded with blood plasma LPS、serum AST、serum ALT’s change, on the contrary, SR gene and protein expression, serum IL-10were the opposite change to blood plasma LPS、serum AST、serum ALT in the model group and4times dose of Jiangzhixiaodu decoction group.④The indicators on the rats in the Jangzhixiaodu decoction group improved better than the indicators on the rats in the Xuezhikang group and simvastatin group.Conclusion:①We can establish successfully alcoholic fatty liver combi-ning intestinal endotoxemia model on rats by the above method. The increase of intestinal mucosal permeability to which various reasons lead is the main reason of increased endotoxin in blood, intestinal endotoxemia plays an important role in alcohol induced liver injury. We can inhibit endotoxin induced liver injury in a certain extent by reducing the intestinal absorption of endotoxin and the endotoxin level in blood.②Jangzhixiaodu decoction has a better curative effect on alcoholic fatty liver combining intestinal endotoxemia model on rats in the the circumstances of interrupting alcohol stimulation and maintaining alcohol stimulation, maybe Jangzhixiaodu decoction can become a new kind of effective drugs on the treatment of alcoholic fatty liver combining intestinal endotoxemia and the prevention alcoholic fatty liver combining intestinal endotoxemia from deterioration;2times dose of Jiangzhixiaodu decoction had the best therapeutic effect on alcoholic fatty liver combining intestinal endotoxemia model on rats;4times dose of Jiangzhixiaodu decoction had the best protective effect on alcoholic fatty liver combining intestinal endotoxemia model on rats; Relationship of dose and effect on therapeutic effect:In the case of no more than2times dose of Jiangzhixiaodu decoction, therapeutic effect increased with increasing dose, in the2times、4time-s and8times of Jiangzhixiaodu decoction group, all groups’ therapeutic effect didn’t show obviously dose effect relationship. Relationship of dose and effect on protective effect:In the case of no more than8times dose of Jiangzhixiaodu decoction, therapeutic effect increased with increasing dose, but, therapeutic effect’s increasing didn’t show multiple relation-ship.③Jiangzhixiaodu decoction can inhibite of enteric LPS into the bloodstream and improve LPS liver injury by improving enteric permeability and maintain enteric integrative; Jiangzhixiaodu decoction can inhibite of the release of cytokine in LPS-TLR4signaling channel and improve LPS liver injury with heightening SR gene and protein expression and IL-10, depressing CD14、TLR4gene and protein expression.④In the the circumstances of interrupting high fat diet and maintaining high fat die, Jangzhixiaodu decoction has a better curative effect on high fat food induced fatty liver model; Jangzhixiaodu decoctionn may also have a good effect on the fatty liver model induced by alcohol and high fat die.