SOCS-3 Expression In The Liver Of NAFLD Rat Model And The Intervention Study Of Rosiglitazone

Backgroud: Nonalcoholic fatty liver disease(NAFLD) is a kind of clinical syndrome which has similar histological changes with Alcoholic fatty liver disease(ALFD),but without over dringking wine. It includes Nonalcoholic fatty liver(NAFL),Nonalcoholic fatty hepatitis(NASH),Nonalcoholic liver cirrhosis. As ever increasing living standard, NAFLD has become one of the most common liver diseases in China even over the world. Although its pathogenesis has been unclear still now, but it is confirmed that NAFLD is associated with insulin resistance and fat deposit in liver is an important part of insulin resistant syndrome. Suppressors of cytokine signaling(SOCS) is a kind of protein that can block JAK-STAT. Recently, people has found that SOCS-3 plays an important part in insulin resistance and NAFLD. Our experiment set up a NAFLD rat model aiming at observing the expression of SOCS-3 in rat liver and therapeutic effects of rosiglitazone,discussing the mechanism of SOCS-3. Through this experiment we want to provide evidence for a new therapeutic target to prevent and cure NAFLD.Objective: To investigate the role of SOCS-3 which is expressed on nonalcoholic fatty liver and the effects of rosiglitazone.Methods: Thirty-seven SD rats were randomized into normal control group(n=8,fed with normal food), rosiglitazone early intervention group (n=8,fed with fat-rich food and rosiglitazone by gastric perfusion), NAFLD group(n=21,fed with fat-rich food). Killed 5 rats of NAFLD group after 8 weeks, and confirmed that the model of NAFLD was successfully established. Then the remaining 16 rats were divided into 2 subgroups: NAFLD group(n=8,fed with continuously with fat-rich food), rosiglitazone late intervention group(n=8, fed with continuously with fat-rich food and rosiglitazone by gastric perfusion). By the end of 16^th weeks, all rats were killed to isolate the serum to test the levels of weight,liver exponent,FBG,FINS,TG,TC. Liver paraffin blades were observed under light microscope. The SOCS-3 mRNA and SREBP-1c mRNA expression of rat liver were analyzed by RT-PCR.Results: 1,Weight,liver exponentWeight of NAFLD group was much higher than normal controlled group (P<0.05) ;weight of rosiglitazone early intervention group and rosiglitazone late intervention group were much lower than NAFLD group (P<0.05 ) ,and these two groups had no significant difference with normal controlled group (P > 0.05) ;thers was no significant difference between rosiglitazone early intervention group and late intervention group (P>0.05) .Liver exponent of NAFLD group was much higher than normal controlled group (P<0.05 ) ; thers was no significant difference between rosiglitazone early intervention group and normal controlled group (P > 0.05 ) ; Liver exponent of rosiglitazone late intervention group group was higher than normal controlled group (P<0.05) ; Liver exponent of rosiglitazone early intervention group and rosiglitazone late intervention group were much lower than NAFLD group (P<0.05) ; thers was no significant difference between rosiglitazone early intervention group and late intervention group (P>0.05) .2. TG,TCTG of NAFLD group was much higher than normal controlled group (P<0.05) ; thers was no significant difference between rosiglitazone early intervention group and normal controlled group (P > 0.05) ;TG of rosiglitazone late intervention group group was higher than normal controlled group (P<0.05) ; TG of rosiglitazone early intervention group and rosiglitazone late intervention group were much lower than NAFLD group ( P < 0.05 ) ; thers was no significant difference between rosiglitazone early intervention group and late intervention group (P > 0.05) .TC of NAFLD group was much higher than normal controlled group (P<0.05) ; TC of rosiglitazone early intervention group rosiglitazone and late intervention group group were higher than normal controlled group (P<0.05) ; TG of rosiglitazone early intervention group and rosiglitazone late intervention group were much lower than NAFLD group (P<0.05 ) ; TC of rosiglitazone early intervention group was lower than late intervention group (P<0.05) .3,FBG,FINS,HOMA-IR FBG of NAFLD group was much higher than normal controlled group ( P < 0.05 ) ; thers was no significant difference between rosiglitazone early intervention group and normal controlled group (P > 0.05) ; FBG of rosiglitazone late intervention group group was higher than normal controlled group (P<0.05) ; FBG of rosiglitazone early intervention group and rosiglitazone late intervention group were much lower than NAFLD group (P < 0.05 ) ; FBG of rosiglitazone early intervention group was lower than late intervention group (P<0.05 ) .FINS of NAFLD group was much higher than normal controlled group (P<0.05) ; FINS of rosiglitazone early intervention group and rosiglitazone late intervention group were much lower than NAFLD group (P<0.05 ) ,and these two groups had no significant difference with normal controlled group (P > 0.05) ;thers was no significant difference between rosiglitazone early intervention group and late intervention group (P>0.05) .HOMA-IR of NAFLD group was much higher than normal controlled group (P<0.05) ; thers was no significant difference between rosiglitazone early intervention group and normal controlled group (P > 0.05) ; HOMA-IR of rosiglitazone late intervention group group was higher than normal controlled group ( P < 0.05 ) ; HOMA-IR of rosiglitazone early intervention group and rosiglitazone late intervention group were much lower than NAFLD group (P<0.05) ; HOMA-IR of rosiglitazone early intervention group was lower than late intervention group (P<0.05) .4,Liver pathologic changes and steatosis gradingUnder the light micro there could be seen bulla fatty liver in NAFLD group with a lot of inflammational cells; in rosiglitazone early intervention group and rosiglitazone late intervention group there were a few hepatic cells steatosis without inflammational cells; steatosis gradings were much lower than NAFLD group (P<0.05) ; steatosis gradings of rosiglitazone early intervention group was smaller than rosiglitazone early intervention group (P<0.05 ) .5,SOCS-3 and SREBP-1c mRNA expressionSOCS-3 mRNA expression of NAFLD group was much higher than normal controlled group (P<0.05) ; thers was no significant difference between rosiglitazone early intervention group and normal controlled group (P > 0.05) ; SOCS-3 mRNA expression of rosiglitazone late intervention group group was higher than normal controlled group (P< 0.05) ; SOCS-3 mRNA expression of rosiglitazone early intervention group and rosiglitazone late intervention group were much lower than NAFLD group (P<0.05) ; SOCS-3 mRNA expression of rosiglitazone early intervention group was lower than late intervention group (P< 0.05) .SREBP-1c mRNA expression of NAFLD group was much higher than normal controlled group(P<0.05 ); SREBP-1c mRNA expression of rosiglitazone early intervention group rosiglitazone and late intervention group group were higher than normal controlled group (P<0.05) ; SREBP-1c mRNA expression of rosiglitazone early intervention group and rosiglitazone late intervention group were much lower than NAFLD group (P<0.05) ; SREBP-1c mRNA expression of rosiglitazone early intervention group was lower than late intervention group (P<0.05 ) .6,correlated analysisSOCS-3mRNA expression was positively correlated with HOMA-IR,SREBP-1c mRNA expression,liver steatosis grading (r= 0.665,0.811,0.831, P<0.05).Conclusion: 1,SOCS-3 might be involved in nonalcoholic fatty liver through up-regulating SREBP-1c mRNA expression and insulin resistance2,Rosiglitazone therapy could decrease the SOCS-3mRNA expression and effectively treat nonalcoholic fatty liver, therapeutic effect was better in early intervention group r than late intervention group.