The Therapeutic Effect Of15-Deoxy-△^12,14-Rostaglandin J₂on Nonalcoholic Fatty Liver Disease In Rats And Its Mechanism

Purpose: To observe the role of15-Deoxy-△^12,14-rostaglandin J₂（15d-PGJ₂） during the treatment of therats with non-alcoholic fatty liver disease （NAFLD） and its effect on the expression of peroxisomeproliferators activated receptor γ （PPARγ）, tumor necrosis factor-α （TNF-α） and interleukin-6（IL-6） in theliver tissue of NAFLD rats.Method:36male Wistar rats of clean grade were randomly divided into group A12and group B24. Ratsin group A were given a normal diet, and rats in group B were given high-fat diet for the construction ofNAFLD rat model. After12weeks of feeding, randomly sample4A rats as control group and6B rats asmodel group. Normal control group and model group rats were sacrificed to detect the weight, liver/bodyweight index, serum TC and TG, LDL, HDL, liver tissue’s TC and TG, ALT, AST, observing the changes inrats liver tissue pathomorphology. After confirming the success of modeling, the remaining8rats of groupA as a normal control group were given normal diet and the remaining16rats in group B （2group B ratsdied in the modeling process） were randomly divided into model control group with8rats andexperimental group with8rats given high-fat diet respectively. The rats of model control group wereinjected intraperitoneally with saline2ml·kg^-1·d^-1. The rats of experimental group were injectedintraperitoneally with15d-PGJ₂10μg·kg^-1·d^-1. Rats in each group were sacrificed after two weeks ofintervention, detecting the weight, liver/body weight index, fasting blood-glucose, serum TC and TG, LDL,HDL, liver tissue’s TC and TG, ALT, AST, observing the changes in rats liver tissue pathomorphology, anddetecting the expressions of PPARγ protein, TNF-α protein and IL-6protein in rats liver tissue withimmunohistochemistry.Results:1. Part one:（1） Body weight: body weight of rats in the model group compared with that of thecontrol group, the difference was not statistically significant （P>0.05）.（2） Liver/body weight index, serumTC and TG, LDL, HDL, ALT, AST：Compared with the control group, the levels of serum TC and TG, LDL,ALT, AST in the model group were higher significantly （P<0.01or P<0.05）, and the serum HDL level inthe model group was significantly lower, the difference was statistically significant （P<0.01）.（3） Hepaticpathological morphology: Compared with the control group, the hepatic steatosis of the model group ratswas significantly severer, the difference was statistically significant （P<0.01）.2. Part two:（1） Body weight: There were no difference in body weight among groups（P>0.05）.（2）Liver/body weight index: Compared with the model control group, the liver/body weight index of theexperimental group rats was significantly decreased, the difference was statistically significant （P<0.01）.（3）Fasting blood-glucose: Compared with the model control group, the fasting blood-glucose level of rats inthe experimental group was decreased significantly, the difference was statistically significant （P<0.01）.（4）Blood lipids: Compared with the model control group, serum TC and TG, LDL levels in the experimentalgroup were decreased significantly, the differences were statistically significant （P<0.05）.（5） Transaminase:Compared with the model control group, the ALT and AST levels of rats in the experimental group weresignificantly reduced, the differences were statistically significant （P<0.01）.（6） TC and TG in liver tissue: Compared with the model control group, the TC and TG levels in liver tissue homogenates of rats inexperimental group of were significantly reduced, the differences were statistically significant （P<0.01orP<0.05）.（7） Hepatic pathological morphology: Compared with the model control group, the hepaticsteatosis of the experimental group rats was significantly improved, the difference was statisticallysignificant （P<0.05）.（8） Compared with the model control group, the liver tissue positive expressionpercentages of PPARγ protein of the experimental group rats was significantly increased, the positiveexpression percentages of TNF-α protein and IL-6protein were significantly decreased, the differenceswere statistically significant （P<0.05）.Conclusion:1. NAFLD rat model could be constructed successfully by feeding with high fat diet for12weeks.2.15d-PGJ₂, a nature ligand of PPARγ，has therapeutical effect on NAFLD in rat.3.15d-PGJ₂canup-regulate PPARγ protein expression in the NAFLD rat liver tissue，thereby inhibiting TNF-α protein andIL-6protein expression in the NAFLD rat liver tissue.