RESUMO
【Objective】 To reveal possible mechanisms of miRNA in diabetic hepatopathy through bioinformatics method. 【Methods】 Subset data of miRNA and their matched mRNAs in the liver of STZ-induced diabetic mice and the normal liver tissues of congenial mice by detecting on microarrays were collected from GEO database； information from the database and bioinformatics analysis were applied to mine a batch of miRNAs in diabetic hepatopathy and targeted mRNAs regulated. Then qRT-PCR was used to verify the expressions of miRNAs in diabetic liver from 20 STZ-treated Kunming mice and 10 normal homologous mice. 【Results】 Via detection and analysis， miRNAs differentially expressed （including 96 up-regulated and 77 down-regulated） were significantly obtained. Groups of miRNAs and their effectors （mRNAs） that may be related to the pathological process of diabetic liver disease in mice were screened by GO and KEGG enrichment analyses， combined with relevant protein annotations in the databases and references. The expressions of miR-200a-3p， miR-200b-3p and miR-222-3p in the mice’s liver tissue detected by qRT-PCR were significantly down-regulated. In addition， the expressions of related effector genes CERS6， MYBL1， SCD2， SLCO1A4 and PLK2 were up-regulated， while the expressions of ACSS2， BCL6 and SLC10A2 were down-regulated. 【Conclusion】 The variation trend of those candidate miRNAs in mouse diabetic liver compared with that in control livers was consistent with that of the previous studies and prediction， which revealed their potential molecular regulation in this disease process.
RESUMO
AIM:To investigate the role of peroxisome proliferator-activated receptors(PPARs)-inflammation signaling pathways in diabetic hepatopathy.METHODS:Diabetic mouse model was established by feeding the mice with a high-energy diet for 4 weeks combined with intraperitoneal injection of streptozotocin(STZ;40 mg· kg-1· d-1for 5 d). The hepatopathy model was confirmed by histopathological observation and the indexes of liver function, such as alanine aminotransferase(ALT),aspartate aminotransferase(AST)and alkaline phosphatase(ALP),after another 4 weeks.Mo-reover,fasting blood glucose(FBG), and serum levels of total cholesterol(TC), triglyceride(TG)and insulin were measured,and the HOMA insulin resistance index(HOMA-IR)was calculated.The mRNA and protein expression levels of PPARs and inflammation-related factors were measured by qPCR and Western blot, respectively.RESULTS: After treatment with STZ for 7 d,the FBG of mice exceeded 11.1 mmol/L,suggesting that the diabetic model was established. After 4 weeks,the structural deformation of the hepatocytes(including hepatocytes containing abundant fat vacuoles, and inflammatory cell infiltration),and the increases in the serum levels of insulin,HOMA-IR,TC,TG,ALT,AST and ALP were observed(P<0.01), indicating the occurrence and progression of hepatopathy in diabetic mice.Meanwhile, com-pared with the control group,the mRNA and protein expression of PPARα,PPARβand PPARγdecreased,but the expres-sion of nuclear factor-κB(NF-κB),cyclooxygenase 2(COX-2)and inducible nitric oxide synthase(iNOS)significantly increased in the diabetic hepatopathy mice(P <0.01).CONCLUSION: Down-regulation of PPARα, PPARβand PPARγand activation of NF-κB-COX-2/iNOS signaling pathways may be involved in the diabetic hepatopathy in mice in-duced by long-term high-energy diet feeding combined with intraperitoneal injection of STZ.