The Pathogenesis Of Insulin Resistance In Rats With Nonalcoholic Fatty Liver Disease And The Effects Of Traditional Chinese Medicine On Them

Background and objective:Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome that has the same pathological changes with alcoholic fatty liver disease (AFLD) , but the patients suffering from it do not get accustomed to drinking. The pathogenesis of non-alcoholic fatty liver disease (NAFLD) was not definite up to now. At present, it was considered to relate to factors as followed: lipid metabolism disturbance,oxidative stress,lipid peroxidation,insulin resistance,releasing cytokines and so on[1]. Recently, more and more research demonstrated that non-alcoholic fatty liver disease has close relationship with leptin and insulin resistance[2,3]. This experiment investigated the role of leptin and insulin resistance in the pathogenesis of non-alcoholic fatty liver disease via the detection of serum leptin level and the expression of leptin receptor as well as peroxisome proliferator-activated receptor ?. Furthermore, this research surveyed that whether the method of disperse the depressed liver-energy,removing blood stasis,deoppilation collaterals and descending the turbid can have any effect on the rats with non-alcoholic fatty liver disease. The aims were to interpret the effect of leptin and insulin resistance in progression of non-alcoholic fatty liver disease (NAFLD) and explore new therapeutic method of traditional Chinese medicine.Methods:All male SD rats were randomly divided into seven groups: high-fat diet model group (M group),low dose treatment group (LT group),middle dose treatment group (MT group),high dose treatment group (HT group),positive control group (PC group),medicine prevention group (P group) and normal control group (C group). Copy the model of non-alcoholic fatty liver disease (NAFLD) with a high-fat diet. The rats with non-alcoholic fatty liver disease (NAFLD) in LT group,MT group,HT group and D group were treated according to low dose, middle dose,high dose and Lipitor respectively from the fifth week, the rats in P group were treated with middle dose traditional Chinese medicine from the first week. These rats were sacrificed at the end of the twelfth week. The levels of serum leptin,fasting blood glucose (FBG) and fasting insulin (FINS) were measured. The insulin resistance was expressed by the insulin resistance index (IRI) of homeostasis model assessment (HOMA). The pathological changes of hepatic tissues were observed under light microscopy by HE staining and sudan III staining; hepatic expressions of leptin receptor (OB-R) and peroxisome proliferator-activated receptor ? (PPAR?) mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR). At the same period, the rats in normal control group were fed with standard diet for twelve weeks.Results: (1)Serum index: Twelve weeks later, the levels of serum leptin(1.82±0.25ng/ml),FBG(5.43±0.56mmol/L),FINS(10.26±4.0mU/L),IRI(0.66±0.23) in the middle dose treatment group were lower significantly than those in the model group(2.57±0.35ng/ml,6.03±0.56mmol/L,21.16±4.19mU/L,1.72±0.27 and P<0.01,P<0.05,P<0.01,P<0.01). (2)Pathology of hepatic tissue: Hepatic steatosis was observed in the model group at the fourth week. From the eighth week to twelfth week, the livers gradually progressed from steatosis to steatohepatitis. (3)Expressions of OB-R and PPAR?mRNA: Twelve weeks later , Rats in M group showed lower OB-Ra and OB-Rb levels in hepatic tissue than those in C group. Furthermore, there were significant negative correlations between serum leptin concentration and expressions of OB-Ra, OB-Rb mRNA in M group. The levels increased significantly in MT group and P group in comparison with those in M group. We found that the pattern of PPAR? mRNA level was downregulated in M group in comparison with those in C group at the end of the twelfth week. And the expressions of hepatic tissue PPAR? mRNA in MT group and in P group were upregulated than those in M group, the difference was significant, but the difference was not significant in comparison with those in C group. Conclusions : (1)Leptin and insulin resistance maybe played an important role in non-alcoholic fatty liver disease (NAFLD). (2)Traditional Chinese medicine was a good treatment for non-alcoholic fatty liver disease (NAFLD). Its mechanism of action may be related to decreasing the level of serum leptin,upregulating the expressions of leptin receptor and peroxisome proliferator-activated receptor ? of hepatic tissue and relieving leptin resistance as well as insulin resistance.