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AIM:To improve the success rate of experimental modeling of non-alcoholic fatty liver(NAFLD)in rats by high-fat diet through comparing three different formulations of high-fat diets in con-structing non-alcoholic fatty liver rats model,so as to provide a reliable animal model for the study of non-alcoholic fatty liver disease.METHODS:SPF-grade male SD rats were divided into four groups randomly:control group,high-fat diet group1(HFD1),high-fat diet group2(HFD2),high-fat diet group3(HFD3).Each group was given the corre-sponding feed for 8 weeks while modeling.The da-ta on general observation,body weight changes,and ingestion of the rats were recorded during the modeling period.After 8 weeks'feeding,liver ultra-sound,CT and MRI examination were performed for the rats of each group to check the status.Blood and liver samples were collected.Changes in liver function(ALT,AST),blood lipids(TC,TG,HDL-C,LDL-C),and inflammatory indexes(IL-1β,IL-6,TNF-α)were detected.The morphology of the liv-ers was observed with the naked eyes,and the liv-er index and Lee's index were calculated at the end of 8 weeks.The effects of different high-fat diets on the establishment of NAFLD model in SD rats were comprehensively evaluated by comparing the difference of above indexes among the groups.RE-SULTS:Compared with the control group,rats in the HFD1,HFD2 and HFD3 groups showed poor mental deterioration,decreased activity,severe hair loss,decreased food intake,increased body weights,and significantly increased liver index and Lee's in-dex,along with increased liver volume,blunt edge,steatosis and lipid deposition,and the trend was even more pronounced in the HFD3 group.Com-pared with the control group,the serum levels of ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α were significantly increased,while the contents of HDL-C was significantly decreased in the HFD1,HFD2 and HFD3 group,especially in the HFD3 group.Com-pared with the control group,the B ultrasonogra-phy showed an enlarged liver with enhanced paren-chymal echo and pipe unsharpness,CT showed that the liver and spleen CT ratio decreased obvi-ously,and the MRI images showed obvious differ-ence of liver signal intensity between in/out of phase image in the HFD1,HFD2 and HFD3 group,and the most significant imaging changes was ob-served in the HFD3 group.CONCLUSION:The above three kinds of high-fat diets can establish NAFLD model in SD rats after 8 weeks'feeding,the models induced by HFD3 was better than those in-duced by the other two groups.NAFLD lesion is rel-atively serious and expected to last longer in HFD3 group,which are more suitable for investigating the underlying mechanisms of non-alcoholic fatty liver disease and development of lipid-lowering drugs.
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AIM:To investigate whether hydrogen sulfide ( H2 S) protects the hearts against inflammatory re-sponses induced by acute myocardial ischemia in isolated rat hearts .METHODS: Rat acute myocardial ischemia injury was induced by ligation of the left anterior descending coronary artery for 4 h, and the normal perfusate was replaced with NaHS (5 μmol/L, 10μmol/L and 20 μmol/L) perfusate accordingly in NaHS groups 2 h after ischemia.The changes of cardiac function in the myocardial ischemic injury rats were observed .The mRNA expression of TNF-α, IL-1β, IL-6, IL-10 and ICAM-1 was detected by real-time PCR.The protein level of nuclear factor-κB ( NF-κB) in the myocardial tissues was detected by Western blotting .RESULTS:The cardiac function in ischemia group was lower than that in sham group (P<0.01).Compared with ischemia group, perfusion of NaHS resulted in the improvement of the cardiac function (P<0.05 or P<0.01).Compared with sham group, the mRNA expression of TNF-α, IL-1β, IL-6 and ICAM-1 in the cardiac tissues was significantly increased , and the mRNA expression of IL-10 in the cardiac tissues was significantly decreased in ischemia group (P<0.01).Compared with ischemia group , the perfusion of NaHS significantly decreased the mRNA ex-pression of TNF-α, IL-1β, IL-6 and ICAM-1 ( P<0.05 or P<0.01 ) .The perfusion of NaHS at concentrations of 10μmol/L and 20μmol/L significantly increased the mRNA expression of IL-10 (P<0.01).The protein level of NF-κB in ischemia group was markedly higher than that in sham group (P<0.01).Compared with ischemia group, the perfusion of NaHS at concentrations of 10 μmol/L and 20 μmol/L significantly decreased the expression of NF-κB ( P<0.05 or P<0.01).CONCLUSION:H2S protects the hearts against acute ischemia injury through inhibition of NF-κB activation and subsequent down-regulation of NF-κB-dependent inflammatory gene expression .
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Aims To observe the changes of endoge-nous hydrogen sulfide/cystathionine-γ-lyase (H2 S/CSE)system and to study the effects of H2 S on cardiac function,H2 S/CSE and myocardial infarct volumes in acute myocardial ischemic injury in isolated hearts of rats.Methods The myocardial ischemic injury model was established by the ligation of coronary artery.The hemodynamic parameters,such as the left ventricular developed pressure (LVDP),±dp/dtmax and coronary arterial flow(CF),were respectively recorded to evalu-ate the cardiac function.The content of H2 S and the activity of CSE in cardiac tissue were detected respec-tively at each time point after ischemia.Infarct vol-umes in isolated rat hearts were determined by dual staining with Evans-blue and TTC.Results (1 )Com-pared with those of the sham group,LVDP,±dp/dtmax and CF were significantly decreased at 30 min,1,2,3, 4 h after ischemia(P<0.01),there were no statistical-ly significant differences in the content of H2 S and the activity of CSE in cardiac tissue at 3 0 min after ische-mia.But during the periods from 1 h to 4h after ische-mia,the content of H2 S and the activity of CSE in car-diac tissue were significantly decreased,the infarct volumes were greatly increased compared with those of the sham control group (P<0.05 or P<0.01 ).(2) Compared with those of the ischemia 4h group,LVDP, ±dp/dtmax and CF were significantly increased in the NaHS low,middle and high dose groups (P<0.05 or P<0.01),the content of H2S and the activity of CSE in cardiac tissue were significantly increased in the NaHS low,middle and high dose groups(P<0.05 or P<0.01 ),and the infarct volumes were significantly decreased in NaHS middle and high dose groups(P<0.01 ).Conclusion H2S and CSE are involved in myocardial ischemic injury in isolated hearts of rats. Administration of NaHS could enhance the activity of CSE,increase the content of H2 S,and reduce infarct volumes.It could be suggested that H2 S has cardiopro-tective effects on acute myocardial ischemic injury.
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Aim To investigate whether hydrogen sul-fide ( H2 S ) inhibits cardiomyocyte apoptosis induced by acute myocardial ischemia in isolated perfused rat heart. Methods The myocardial ischemia injury model was replicated with Langendorff isolated perfused rat heart, and the left anterior descending coronary ar-tery was ligated for 4 h. 40 male SD rats were divided into five groups randomly: sham group, ischemia group, and NaHS groups (5,10,20μmol·L-1). The segmental heart samples were used for HE staining. Cardiomyocyte apoptosis was detected with TUNEL as-say. The expressions of caspase-3 and Cyt-C in hearts were determined with Western blot analysis. Results Myocardial cells were found to show serious disorder and coagulated zonal necrosis under light microscope, the apoptotic rate of cardiomyocytes and the expression of caspase-3 and Cyt-C were significantly increased af-ter ischemia for 4h. Perfusion of NaHS resulted in more clear cell morphology and milder pathologic chan-ges of myocardiocytes according to the HE staining a-nalysis, and the significant decrease of expression of Cyt-C. After perfusion of 10,20 μmol·L-1 NaHS,the apoptotic rate of cardiomyocytes and the expression of caspase-3 were significantly decreased. Conclusion H2 S has certain protective effects on acute myocardial ischemic injury in isolated perfused rat heart via inhibi-ting cardiomyocyte apoptosis.