Study on berberine regulating relationship between UCP2 and mitochondrial dynamics in skeletal muscle and kidney of mice with ischemia-reperfusion
Objective To investigate the effects of berberine on UCP2 expression and the mitochondrial dy-namics in skeletal muscle and kidney in mice with ischemia reperfusion injury (IRI) of lower limb.Methods Thirty male Kunming mice were randomly divided into the negative control group,the positive control group,and low,medium and high doses berberine intervention groups.The mice in all experimental groups constructed the ischemia reperfusion injury model of lower limbs by tourniquet,different doses of berberine solution were injected intraperitoneally for intervention,while the ischemia repeating supply group used normal saline for re-placement.The HE staining was used to detect the pathological conditions of skeletal muscle and kidney,PCR and Western blot were used to detect the gene and protein expression levels of UCP2,FIS1,DRP1,Mfn1 and Mfn2,and the changes of SOD,MDA and GSH were detected by kit.Results After IRI intervention in the both lower extremities,the inflammatory cell infiltration occurred in both skeletal muscle and kidney,and the cell structure of skeletal muscle showed the damage changes.Meanwhile,the gene and protein expressions lev-els of UCP2,FIS1 and DRP1 and the levels of GSH and SOD in skeletal muscle were significantly increased (P<0.05),while the gene and protein expression levels of Mfn1 and Mfn2 and the levels of MDA were signif-icantly decreased (P<0.05).The increase of UCP2 and DRP1 gene and protein expression levels in kidney was different (P<0.05).Berberine could up-regulate the UCP2 gene expression in skeletal muscle and the pro-tein expression in skeletal muscle (P<0.05).At the same time,DRP1 gene and protein were significantly inhibited in the kidney tissue (P<0.05),but which in skeletal muscle had no significant change.Conclusion IRI of skeletal muscle of lower extremity in mice leads to severe oxidative stress injury,mitochondrial dynamic imbalance and inflammatory damage of kidney in the injured parts.The therapeutic effect of berberine on skeletal muscle and kidney IRI may be achieved by inhibiting oxidative stress injury,in which its protective effect on kidney may also be related to inhibit the expression of DRP1 after UCP2 up-regulation,thus limit the mitochondrial fission and slow down the development of injury.
万方数据
维普
