Preliminary study on the mechanism of PANoptosis occurrence in testicular tissue of type Ⅰ diabetes mellitus
Objective To explore the possible mechanism of PANoptosis ocurrence in testicular tissue of type Ⅰ diabetes mellitus(T1DM).Methods Fifty SPF-grade SD rats were randomly divided into the control group(n=15)and type 1 diabetic group(n=35).After 8 weeks of successful modeling,testicular tissues were collected for detecting PANoptosis-related indexes as well as PI3K,AKT and NF-κB expressions.GC-1 spg cells were divided into a control group,a hyperglycemic group(HG),and a LY294002 and hyperglycemic group(LY294002+HG);CCK-8 experiments were used to determine the optimal concentration and time of PI3K inhitbitor(LY294002);Intracellular PANoptosis-related indexes and PI3K,AKT,NF-κB expressions were examined,respectively.Results For in vivo animal experiments,PANoptosis-related immunohistochemical indexes,mRNA and protein expressions in testicular tissues in the T1DM group were all significantly higher than those in control group;Immunohistochemical indexes,mRNA and protein expressions related to PI3K/AKT/NF-κB signaling pathway were also elevated in testicular tissues in the T1DM group.For in vitro cell tests,caspase-1 expression within the GC-1 spg cells was upregulated in the HG group compared with the control group;The expressions of PANoptosis-related proteins and PI3K,AKT and NF-κB were increased in GC-1 spg cells of the HG group;But the expressions of the above proteins were all decreased in the LY294002+HG group compared with the HG group.Conclusion The occurrence of PANoptosis in testicular tissue of type I diabetic rats may be mediated by the activation of PI3K/AKT/NF-κB signaling pathway.
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