Effects Of Taurine On Liver Injury In Type2Tiabetic Mice

Objectives The aims of this study is to observe the influences of Taurine on hepaticdamage of T2DM mice and the expression of Mfin2,Drp1and Fis1,and explore thepossible mechanism through spontaneous mice model of type2diabetes.Methods Randomly selected12female db/db mic only13weeks of age,matching thosemice are divided into Taurine treatment group and vehicle treatment group.db/db diabeticmice as the research object,phenotypically normal db/m mouse(lepr-/m)as the normalcontrol.Each kind of mice were randomly divided into the Taurine treatment group andvehicle treatment group (VEH).Methods: Taurine200mg/kg/day gavage,for3consecutiveweeks,vehicle control group with the same methods is given the same dose of normalsaline solution.Mice were detected for20days weight,blood sugar changes.Measurementof serum triglyceride (TG),total cholesterol (TC),alanine aminotransferase(ALT),aspartateaminotransferase(AST)values,plasma glycation end products(AGEs).Horizontal Detectionof liver tissue malondialdehyde (MDA),reactive oxygen species (ROS) levels,superoxidedismutase (SOD),xanthine oxidase (XOD) vitality,hepatic TG and TC levels;Observechanges of liver tissue morphological by Light microscopy;Hepatic lipid deposition withoil red O staining;Hepatic apoptosis observed by TUNEL.Expression was observed in livertissue Mfn2,Drp1,Fis1,AGEs and RAGE proteins using immunohistochemical staining(immunohistochemistry,IHC),application of real time-PCR method to detect the expressionof liver tissue Mfn2and Fis1.Results1The changes of each animal weight,glucose,lipids and liver function.Compared with lean+VEH group,in db/db+VEH group,Compared with db/db+VEHgroup, in db/db+TA group,ALT, AST decreased, total cholesterol and triglyceride in livertissue decreased (P<0.05),and although triglyceride,total cholesterol in plasma have somechanges, but there was no statistical significance.2Changes of hepatic tissue morphology.Light microscopy showed there were edema,cytoplasmic loose lightly stained andballooning cell disorder congestion, inflammatory cell infiltration,sinus narrows andvisible fusion of lipid droplets in hepatocyte in liver from the db/db+VEH group.oilred O staining revealed a large stained red small lipid droplets;Compared withdb/db+VEH group,in db/db+TA group,under the light microscope,hepatocyte edema, inflammatory cell infiltration reduction,occasionally fatty degeneration;oil red O stainingshowed hepatic lipids particles reduced.3Hepatocyte apoptosis. TUNEL staining showedthat the liver tissue of db/db+VEH group has more apoptosis and cellular nucleus wasbrown; hepatic cell apoptosis reduced significantly in db/db+TA group.4Index relatedto oxidative stress. Compared with lean+VEH group, in db/db+VEH group,MDA,XODand ROS were significantly increased,SOD decreased significantly (P<0.05);Comparedwith db/db+VEH group,in db/db+TA group,the content of MDA,XOD and ROS isreduced,the activity of SOD increased (P<0.05).5The expression of proteinDrp1,Fis1,AGEs and RAGE in hepatic tissue. Compared with lean+VEH group,indb/db+VEH group,the expression of protein Drp1,Fis1,AGEs and RAGE in hepatic tissuewere up-regulated and the expression of Mfn2was down-regulated Byimmunocytochemistry(P<0.05);compared with db/db+VEH group,in db/db+Taurinegroup,the expression of protein Drp1,Fis1,AGEs and RAGE were down-regulated andthe expression of Mfn2was up-regulated by immunocytochemistry (P<0.05).6Theexpression of Mfn2mRNA and Fis1mRNA in different group.Real-time PCR resultsshowed that compared with lean+VEH group,in db/db+VEH group,the expression of Fis1and Fis1mRNA was upregulated and Mfn2mRNA decreased (P<0.05);Compared withdb/db+VEH group,in db/db+TA group,the expression of Fis1mRNA decreased and mfn2mRNA was up-regulated (P<0.05).Conclusions1Protective effects of taurine on the liver in T2DM mice is by itsinhibition of hepatic oxidative stress,reducing AGEs-RAGE interaction,improvingmitochondrial fusion/fission processes.2Mitochondrial fission Drp-1and Fis1genes areupregulated and Mfn2fusion gene is downregulated in the liver of type2diabetic mice,This change prompted mitochondrial fission,fusion imbalance may be involved in type2diabetes incidence of liver injury in mice.3Enhanced mitochondrial fission process withoxidative stress and promote each other, this change involved in the occurrence of liverinjury in T2DM mice.