Effects Of Schistosoma Japonicum Infection On TNF-α, NF-κB And YM-1mRNA In Diet-induced Fatty Liver Of C57BL/6J Mice

Objective To observe the pathological structure, biochemical indicators, and changesof tumor necrosis factor-α（TNF-α), nuclear factor-kappa B (NF-kB) and macrophageM2marker, specifically Ym-1, and explore the relationship and mechanism ofmacrophage polarization and insulin resistance in diet-induced obese and schistosomajaponicum infected C57BL/6J mice．Methods36male C57BL/6J mice were randomly assigned into3groups: normalcontrol (NC, n=12) group, high-fat diet (HF, n=12) group and high-fat diet withschistosoma japonicum infected (HSj, n=12) group. They were fed with basic diet,high-fat diet group, respectively, and HSj group were infected schistosoma japonicum.Specimen was collected6and12weeks after high-fat diet, separately. The levels offasting blood glucose (FBG), fasting plasma insulin (FINS) and insulin (HOMA-IR)were detected and the contents of liver homogenate alanine aminotransferase (ALT),triglyceride (TG) and cholesterol (TC) were measured. The pathological changes ofliver were observed by HE staining. TNF-α, NF-kB and Ym-1mRNA were detected bysemi-quantitative reverse transcription polymerase chain reaction (RT-PCR).Results1. When having been fed for6weeks, the weight of HF and HSj group increased20%than the NC group, and obesity model mice were obtained.12weeks after feeding,the weight of HF group increased than the NC group (P<0.05), while HSj groupreduced than HF group (P<0.05), but no significantly difference between NC group(P>0.05). 2.6weeks after feeding, the level of FINS and HOMA-IR in HF group were higherthan NC group (P<0.05), while FBG had no significant difference (P>0.05); In HSjgroup, the HOMA-IR were significantly decreased when compared with HF group(P<0.05), while there were no significant difference in FBG and FINS. The level ofFBG, FINS and HOMA-IR in HF group were significantly higher compared withNC group after12weeks (P<0.05). At the same time, the level of FBG, FINS,HOMA-IR in HSj group decreased compared with HF group (P<0.05).3. Liver homogenate were collected6and12weeks after feeding. The concentrationof TG in HF group was significantly higher than NC group (P<0.05), and levels ofTC and ALT had no significant difference between HF group and NC group6weeksafter feeding (P>0.05). The levels of TC and TG in HSj group were lower than HFgroup, while there was no significant difference in ALT after6weeks (P>0.05).After12weeks, the levels of TC, TG and ALT in HF group were significantlyhigher when compared with NC group (P<0.05); In HSj group, TC and TG werefound significantly lower than HF group, while ALT level was higher than the HFgroup (P<0.05).4. When6th week, liver of NC mice was ruddy, and edge dull, pale yellow and spotswere visible in HF group, while reddish-brown, particles nodules, smaller volumethan HF group were observed in liver of HSj mice; After12weeks, the liver of NCgroup was normal, while HF and HSj group had poor conditions than6th week.5. After having been fed for6and12weeks, the HE staining under an opticalmicroscope showed that there were no abnormalities of liver in NC group.6th week,varying sizes of hepatocyte lipid droplets were observed in HF group, which weremore obvious and ballooning degeneration with fibrosis were visible after12weeks;We found few lipid droplets of varying sizes and hepatocyte necrosis in HSj groupafter6weeks, and poor conditions after12weeks. There were lobular and periportal inflammatory cell infiltration in the HF group6th week and12th week, which werepoor than HSj group.6. The expression of TNF-α mRNA and NF-kB mRNA in HF group were higher thanHSj group and NC group (P<0.05). The expression of Ym-1mRNA in HF groupwas higher than NC group and HSj group after6weeks(P<0.05), but it was intensityexpression12weeks (P <0.05), and higher than6weeks (P <0.05).7. A positive and significant correlation was observed between the HOMA-IR andTNF-α mRNA in HF mice (P<0.05), no relationship with NF-kB mRNA, meanwhile,negatively relationship was found between HOMA-IR and Ym-1mRNA in HSj mice(P <0.05).Conclusion1. We could obtain obese and fatty liver C57BL/6J mice model by high-fat diet, and thismodel had the features of insulin resistance.2. There was certain relationship between the expression of TNF-α and NF-kB mRNAand liver-derived insulin resistance.3. We found that M2macrophages expressed higher while inflammatory factors andcharacteristics of insulin resistance weaken in schistosoma japonicum infected mice,and this may be related to the M2macrophages inhibition of pro-inflammatoryeffect of M1macrophages, But schistosoma japonicum infection may aggravateliver necrosis and hepatic fibrosis.