| For various reasons,without alcoholism history,excessive accumulation of lipid in the liver,leading to changes the shape and function of the liver.This situation called Nonalcoholic fatty liver disease(NAFLD).In animal husbandry production,fatty liver endanger the health of the animal,reduce the egg laying rate,affect the health of dairy cows perinatal and endanger the lives of dogs and cats.At present,the pathogenesis of NAFLD has not been fully discovered.Therefore,this status caused the lack of effective method of treatment.Sodium alginate(SA)is a natural marine polysaccharide,with weight loss and lipid-lowering effect,is currently used as food additives.In order to investigate the therapeutic effect of SA on NAFLD,NAFLD rat model was established by feeding high fat diet.The effects of SA on liver lipid metabolism and possible mechanism were investigated by different concentrations of SA aqueous solution.The pathological changes of liver and the ultrastructure of hepatocytes were observed.Serum levels of serum lipids and liver enzymes were measured.Determination of the expression of genes associated with lipid metabolism in the liver.The function and effect of SA on liver lipid metabolism can be studied by the results of the measurements.A total of 126 SD rats were divided into 6 groups(21 rats in each group).Including normal control group(NC),high fat model group(HF),sodium alginate group I(SA-I,33.75 mg/kg),sodium alginate group II(SA-II,67.5 mg/kg),sodium alginate group III(SA-III,135 mg/kg)and sodium alginate group IV(SA-IV,270 mg/kg).Add high-fat diet to feed 2 weeks model,the use of different concentrations of sodium alginate treatment.Every 7 rats were killed when medication to rats in the first 4 weeks,6 weeks and 8 weeks.The degree of liver lesion were observed by HE staining.The levels of serum and lipid were measured by biochemical method.The expression of lipid metabolism related genes in liver were determined by the ultrastructure of liver tissue real-time fluorescence quantitative PCR.Specific results are as follows:(1)The result of effects of different concentrations of SA on body weight and liver weight of NAFLD rats as follow: at 8 weeks,the body weight of HF group was significantly higher than that of NC group(P < 0.05).Each group was able to reduce the weight gain caused by high fat diet(P < 0.01).After treatment with SA at 4 weeks,6weeks and 8 weeks,the liver weight of HF group were very significantly higher than those of NC group(P < 0.01).After SA treatment 4 weeks,SA-IV HF group was significantlylower than(P < 0.05),post-treatment SA 6 weeks,SA-IV HF group was significantly lower than(P < 0.05).After treatment with SA for 8 weeks,SA-IV group and SA-III group were very significantly lower than those in HF group(P < 0.01).After treatment with SA for 4 W,6 W and 8 W,The liver index of HF group was very significantly higher than that of NC group(P < 0.01).And there was no significant difference between HF group and HF group(P > 0.05).(2)The results of blood lipid levels as follows: After SA treatment 4 W,SA-I serum HDL levels were significantly higher than HF group(P < 0.05),and NC group was very significantly higher than HF group(P < 0.01).SA treatment after 6 weeks,NC group,SA-III and SA-I were significantly higher than HF group(P < 0.05).And SA-II group was very significantly higher than HF group(P < 0.01).After SA treatment of 8 weeks,SA-IV and SA-III were significantly higher than HF group(P < 0.05).The levels of serum LDL in NC group and treatment group were very significantly lower than those in HF group at 4weeks and 8 weeks(P < 0.01).After treatment with SA for 6 weeks,NC group was very significantly lower than HF group(P < 0.01).And SA-III group was significantly lower than HF group(P < 0.05).After treatment with 4 weeks and 8 weeks,the levels of serum TC in the NC group and the treated group were significantly lower than those in the HF group(P < 0.05).SA treatment after 6 weeks,the levels of serum TC group NC,SA-IV and SA-III was significantly lower than HF group(P < 0.05).After treatment with 4 weeks and 8 weeks,the serum TG level in NC group was very significantly lower than that in HF group(P < 0.01).After treatment with 4 weeks,6 weeks and 8 weeks,the serum TG level in the treatment group was very significantly lower than that in HF group(P < 0.01).(3)The results of serum alanine aminotransferase and aspartate aminotransferase were as follows: the levels of serum ALT in NC group and treatment group were significantly lower than those in HF group at 4 W and 8 W(P <0.05).SA treatment after 6 weeks,the level of serum ALT in SA-IV group was significantly lower than that in HF group(P<0.05),while that in NC group and SA group was very significantly lower than that in HF group(P <0.01).The levels of serum AST in NC group and treatment group were significantly lower than those in HF group at 4 weeks and 8 weeks(P <0.05).After treatment with SA for 6 weeks,NC group was very significantly lower than HF group(P<0.01).(4)The results of Electron microscopy as follow.There were a few or no lipid droplets in the liver cells of group NC rats,and the number of mitochondria was more.The mitochondria and rough endoplasmic reticulum were clear and the mitochondrial ridge wasmore.Compared with group NC,the cytoplasm of HF group contains a lot of lipid droplets,and the lipid droplets are larger.The mitochondria are greatly reduced and the mitochondria of liver cells are swollen.The mitochondrial cristae is reduced,fracture and disappear.The rough endoplasmic reticulum were expansion and fracture.Compared with HF group,the dosage of each group was significantly improved.The intracellular lipid droplets became smaller and number of mitochondria increased.The swelling was alleviated,the number of mitochondrial ridge increased,and the structure was clear.(5)Expression of lipid metabolism-related gene mRNA in liver: After 4 weeks of treatment with sodium alginate,the expressions of ACC,FAS,SCD1 and SREBR-1c in the liver of group NC,group SA-II and group SA-III were significantly lower than those of group HF(P < 0.05).The expression of CPT1 in SA-I group was significantly higher than that in group HF(P < 0.05),and the NC group,SA-III and SA-II group were significantly higher than those in group HF(P < 0.01).After 6 weeks of treatment with sodium alginate,the expressions of ACC,FAS and SCD1 in the liver of group NC,group SA-II and group SA-III were significantly lower than those in group HF(P < 0.05),the expression of SREBR-1c in liver of group NC and treatment group was significantly lower than that in group HF(P < 0.01).The expression of CPT1 in liver of SA-II and SA-III groups was significantly higher than that in group HF(P < 0.01).After 8 weeks of treatment with sodium alginate,the expressions of ACC,FAS,SCD1 and SEBER-1c in the rat livers of SA-III and SA-II were significantly lower than those in group HF(P < 0.05).The expression of FAS and SEBER-1c in NC group was significantly lower than that in group HF(P < 0.05).The expression of CPT1 in liver of SA-III and SA-II was significantly higher than that in group HF(P < 0.01).From the above results,the therapeutic effect of SA on NAFLD mainly lies in the following two aspects.SA aqueous solution can improve hepatic steatosis,promote mitochondrial recovery and reduce liver injury in NAFLD rats by up-regulating the SEBER-1c gene and its regulation ACC,FAS and SCD1 gene expression,down-regulation of CPT1 gene expression,inhibition of lipid in the liver from the beginning of synthesis and promote liver fat metabolism. |
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