Dynamic Observation Of Changes In The P450Enzymes In The Process Of Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a common type of liver disease associatedwith metabolic stress, genetic, environmental and other factors. Excessive accumulationof lipid in liver cells leading lipid to metabolism disorder, which affects the liverfunction. In some patients this metabolism disorder can cause the disease from thefurther development of simple steatosis to non-alcoholic steatohepatitis (NASH), liverfibrosis, cirrhosis, severe cases may eventually lead to a series of pathological syndromeand the need for a liver transplant. With people’s living standards improving, NAFLDhas become one of the chronic liver diseases which cannot be ignored in China; it is aserious threat to the people’s health.As the most important bio-oxidation enzyme in liver microsomes, cytochrome CYP450enzymes involved in metabolism and closely related to NAFLD pathogenesis, it is aparticipatory endogenous substance and exogenous substances metabolic enzymes thatcan be induced or suppressed by certain compounds. CYP450enzymes mediated lipidoxidation and the generation of oxygen free radicals and led the liver cell apoptosis,then led a series of pathological findings of liver fibrosis, cirrhosis and others. InNAFLD incidence process, the activity of the CYP450enzymes also sufferedinterference of various pathological factors, different subtypes have different activity,and the findings of the same subtype is also controversial in previous studies at home and abroad.In this experiment, we use the fat emulsion to induce non-alcoholic fatty liver model ofSD rats, and use probe method to observethe metabolic status of probe drug, we exploreactivity changes of CYP1A2and CYP2D6which closely related to NAFLD cases in theprocess of NAFLD incidence, that provide the basis for the study of both mechanismsand NAFLD clinical treatment. The main contents summarized as follows:1. Activity status of CYP1A2in the process of NAFLDPreparation of non-alcoholic fatty liver rats’ model, at week0,7,9,11,13,15,17, ratswere given the probe drugs phenacetin respectively in accordance with the unit of bodyweight. Compared with their selves, with the progression of NAFLD, activity ofCYP1A2in the model group reached the highest (15.02±3.12mg/kg) at week9whichis nearly moderate fatty liver period, significantly higher than week0(10.03±3.60mg/kg); compared with normal control group, the probe drug metabolism is alsosignificantly higher than the normal group (9.96±4.00mg/kg) at week9, and graduallyreduced from then on. Liver incubated in vitro experiments also obtained similar results.These differences with normal indirectly explain that activity of CYP1A2firstsignificantly increased and then gradually decreased in the process of NAFLD.2. Activity status of CYP2D6in the process of NAFLDExperiment by observing the metabolic status of α-OH metoprolol in urine, the unitweight of α-OH metoprolol metabolic rate increased significantly with progression ofNAFLD in model group. Compared with week0(4.10±1.24mg/kg) that in the severefatty liver period, α-OH metoprolol metabolic rate was significantly increased at week 9(5.94±2.67mg/kg) and achieved the highest (7.97±1.05mg/kg) at week17. Liverincubated in vitro experiments also obtained similar results. This result indirectlyshowed that with the aggravation of steatosis, CYP2D6activity gradually increased.