Effects Of Selenium On Cardiac Pyroptosis,Autophagy And Apoptosis Under Cadmium Stress In Rabbits

In order to investigate the protective effect of selenium on cadmium-induced cardiac injury,the effects of trace element levels,morphological changes,antioxidant capacity and programmed cardiac death in rabbit hearts.All 40 rabbits were randomly divided into four groups:Control group,Se(0.5 mg?kg^-1?BW)group,Cd(1 mg?kg^-1?BW)group,and Se+Cd group.After 30 days of feeding,the levels of trace elements in heart tissue were measured by ICP-MS.Cytopathological changes were observed by tissue sections and transmission electron microscopy.T-SOD,CAT,GSH-Px,GSH and MDA were measured by the kit Levels.TUNEL assay was conducted to measure the apoptotic level.Immunohistochemical method and immunofluorescence method were used to observe Caspase-1 and LC3Ⅱexpression.Additionally,the expression levels of pyroptosis,autophagy and apoptosis-related genes were detected by real-time fluorescence quantitation and Western blotting in each group.The results of HE staining showed slightly blurred myocardial fibersand the mitochondrial cristae were disorganized and vacuolar.Compared with the control group,the activities of T-SOD,CAT,GSH-Px and the level of GSH in group Cd were significantly inhibited,and the content of MDA was significantly increased（P<0.05）.The results showed that the expression levels of pyroptosis-related genes and proteins（Caspase-1,IL-1β,IL-18and NLRP3）in Cd group were significantly increased（P<0.05 or P<0.01）.Autophagy level showed that the expression levels of related genes（ATG3,ATG5,ATG7,ATG12,Beclin-1,LC3Ⅰand LC3Ⅱ）and proteins（Beclin-1 and LC3Ⅱ/LC3Ⅰ）in Cd group were significantly increased（P<0.01 or P<0.001）.The levels of these genes and proteins in Se+Cd group were significantly decreased（P<0.05）.At the same time,the immunofluorescence results showed that LC3 was localized in the nucleus,and the concentration of LC3 in Cd group increased.Apoptosis results showed that the number of positive apoptotic cells in Cd group was significantly increased.The levels of pro-apoptotic genes（Bax,caspase-3 and caspase-9）and proteins（Bax,Cleaved caspase-3,caspase-9 and Cleaved caspase-9）were significantly increased（P<0.05 or P<0.01）.The expression level of Se+Cd group was significantly decreased（P<0.05 or P<0.01）.In addition,compared with the control group,the protein expression levels of p-Akt/Akt and p-PI3K/PI3K in Cd group were significantly increased（P<0.01）,while those in Se+Cd group were significantly decreased（P<0.05）.The addition of Se alleviated the disorder of trace elements,improved the morphological structure of cells,enhanced the antioxidant capacity,alleviated the degree of programmed cell death,and positively regulated the PI3K/AKT/PTEN pathway.In conclusion,this study confirmed that Se can inhibit Cd-induced oxidative stress,cell pyroptosis,autophagy and apoptosis through the PI3K/AKT/PTEN signaling pathway.