Roles of prostaglandin B2,15-keto-prostaglandin E2,and 8-isoprostane F2α in non-alcoholic fatty liver disease
Objective To investigate the effect of prostaglandin family(PGs)on non-alcoholic fatty liver disease(NAFLD).Methods HepG2 cells,a human hepatocellular carcinoma cell line,were used as the research subject.The experiment was set up as a control group(Ctrl),fatty change group(FFA),prostaglandin B2(PGB2,10 μg/mL)treatment group,15-keto-prostaglandin E2(15-keto-PGE2,10 μg/mL)treatment group,and 8-iso-prostaglandin F2a(8-iso-PGF2α,10 μg/mL)treatment group.Cell activity was determined by the thiazolyl blue(MTT)assay and lipid deposition was detected by the oil red O staining.The expression levels of inflammatory factors and phosphorylated insulin receptor substrates(p-IRS)were determined by real-time fluorescence quantitative PCR(qRT-PCR)and Western blot,respectively.In addition,15 SPF-grade male C57BL/6J mice were randomly divided into a basic group(CD group,n=5,fed with 10％low-fat forage for 16 weeks),high-fat group(HFD group,n=5,fed with 60％high-fat forage for 16 weeks to model NAFLD),and PGB2 group(n=5,given 20 μg/kg PGB2 daily by tail vein injection for 2 weeks after 16 weeks of 60％high-fat diet feeding).The glucose tolerance level of the mice was detected by the intraperitoneal glucose tolerance test(IPGTT)and the degree of hepatic steatosis was determined by HE staining.Results Oil red O staining showed that PGs had no sig-nificant effect on the lipid deposition of NAFLD,but PGs were able to alleviate the inflammation associated with NAFLD.qRT-PCR re-sults showed that compared with the Ctrl group,the levels of IL-1β in the FFA group increased by 2.274±0.550 times(P=0.002 8),while under the action of 50 μg/mL PGB2,10 μg/mL 15-keto-PGE2 and 10 μg/mL 8-iso-PGF2α,the levels of IL-1β decreased to 0.720±0.036 times(P=0.003 1),0.857±0.225 times(P=0.006 4),and 1.767±0.725 times(P=0.029 7),respectively.Western blot results showed that after PGs treatment,the expression level of p-IRS protein was increased.The body weights of mice in the CD group,HFD group and PGB2 group were(28.560±2.028)g,(49.300±0.667)g,and(40.840±4.043)g,respectively,with statisti-cally significant differences between the groups(P=0.001 7).Moreover,the glucose tolerance results in the PGB2 group were better than those in the HFD group.HE staining results showed compared with the HFD group,the degree of hepatic steatosis in the PGB2 group was reduced.Conclusion PGB2,15-keto-PGE2,and 8-iso-PGF2α in the prostaglandin family can alleviate the occurrence and development of NAFLD by alleviating IL-1β-mediated inflammation,upregulating the expression of p-IRS,promoting the transmission of insulin signaling,and attenuating insulin resistance.
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