ABSTRACT
Objective To establish the nonalcoholic fatty liver disease(NAFLD) model in SD rats and to investigate if endoplasmic reticulum stress(ERS) plays a role in the pathogenesis of NAFLD. Methods A total of 36 male SD rats were randomly divided into 4 groups: normal control group 1(N1,n=8), normal control group 2 (N2,n=8), model group 1(M1,n=10) and model group 2(M2,n=10). The two control groups were fed with normal diets, whereas the two model groups were provided diets enriched in fat (10% lard oil and 2% cholesterol). The rats in N1 and M1 groups were sacrificed at the 12th week, and those in N2 and M2 groups were sacrificed at the 20th week. The serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), total protein (TP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) were measured. The steatosis, immflamation and fibrosis of the liver were observed with HE and Masson staining. The expressions of GRP78, CHOP and procaspase-12 mRNA were tested using real-time PCR and the activation of procaspase-12 protein was detected by Western blot. Results At the 12th week, the liver index and the serum levels of ALT, AST,ALP,TP,TC,LDL in M1 group were significantly higher than those in N1 group (P<0.01), but HDL level was significantly lower in M1 group than that in N1 group (P<0.01). At the 20th week, the concentrations of TC and LDL in M2 group were significantly increased in comparison with N2 group. The histochemical study revealed that the hepatic steatosis and inflammation in M1 and M2 groups were more serious than those in N1 and N2 goups(P<0.01). The slight fibrosis was seen in M2 group. At the 12th and 20th weeks, the expressions of GRP78,CHOP and procaspase-12 mRNA and protein in M1 and M2 groups did not differ in N1 and N2 groups. Conclusions The fat-rich diet might successfully induce NAFLD in rats and there is no ERS observed in the study, which suggests that ERS may not be involved in the pathogenesis of NAFLD.
ABSTRACT
Objective To investigate the expression of transforming growth factor β1,transforming growth factor beta receptor(TBR)Ⅰ,TβR Ⅱ,Smad4 and C-Jun in rats with nonalcoholic fatty liver disease(NAFLD)and to find out the mechanisms of liver fibrosis in patients with NAFLD.Methods A total of 18 male SD rats were randomly divided into normal control group(n=9)and model group(n=9).The rats in control group were fed with normal diet,and those in model group were fed with fat-rich diet(consisted of 10%lard oil+2%cholesterol).An rats were sacrificed at the 20th week.The levels of TGFβ1,TβR Ⅰ and TβR Ⅱ mRNA were examined by RT-PCR.The expressions of TGFβ1 and Smad4 in liver tissue were detected by immunohistochemistry.The expression of C-Jun protein was detected by Western blotting.Results The NAFLD model was successfully established.The immunohistochemistry examination revealed that TGFβ1 and Smad4 were expressed weekly in control group,but strongly expressed in model group.RT-PCR showed that A values of TGFβ1,TβR Ⅰ and TβR Ⅱ mRNA were 0.46±0.12,5.z4±2.70 and 3.35±1.95,respectively,in model group,which were higher than those in control group(0.21±0.09,1.36±0.77 and 0.52±0.19,all P values＜0.01).The Western blotting results demonstrated that the expression of C-Jun protein in model group(0.93±0.41)was higher than that in control group (0.32±0.25,P=0.001).Conclusion TGFβ1/Smad4 signal pathway might be involved in the development of hepatic fibrosis in NAFLD.Blocking TGFβ1/Smad4 signal pathway will be helpful in treatment of NAFLD.
ABSTRACT
Objective To investigate the relationship between clinical presentation and pathological characteristics in HBeAg negative chronic hepatitis B(CHB) patients with steatosis, and to find out the predictors of hepatic inflammation and fibrosis. Methods HgeAg negative CHB patients with (n=56) or without (n=60) steatosis confirmed clinically and pathologically were enrolled in the study. All patients were examined for fasting blood glucose(FBG), fasting insulin (FINS), triglyceride (TG), cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyhransferase (GGT), alkaline phosphatase (ALP) albumin (Alb), globulin(Glb), homeostatic model assessment of insulin resistance (HOMA-IR), HBV-DNA and body mass index(BMI). The association of above parameters with hepatic inflammation, fibrosis and fatty deposition were analyzed statistically. Results It was demonstrated that BMI, FBG, FINS, TG, TC, GGT, ALP , Glb and HOMA-IR were significantly higher in HBeAg negative CHB patients with steatosis than those without steatosis (P<0.05). Whereas the levels of HBV-DNA, Alb, ALT and AST were significantly lower in HBeAg negative CHB patients with steatosis compared with those without steatosis (P<0.05). The hepatic inflammation and fibrosis were aggravated in patients with steatosis. It was implicated that BMI,FBG, FINS, TG, TC, GGT and HOMA-IR(all P values 0.05) were significant predictors for hepatic steatosis, while ALT, AST, Glb and HBV-DNA(all P values <0.05) were significant predictors for hepatic inflammation. And the predictors for hepatic fibrosis were ALT, AST, Alb, Glb and HBV-DNA(all P values <0.05). Conclusions Hepatic steatosis is common in HBeAg negative CHB patients which is positively associated with parameters including BMI, FBG, FINS, TG, TC, GGT, ALP and HOMA-IR. Besides steatosis, the hepatic inflammation and fibrosis are also aggravated in these patients.