PINK1/Parkin通路介导的线粒体自噬在十溴联苯醚诱导肉鸡肾脏损伤中的作用.

[Objectives] The aim of this study was to investigate the effects of decabromodiphenyl ether(BDE-209) exposed to broilers on kidney damage,and to explore the potential nephrotoxicity and mechanisms. [Methods] One day-old 150 male AA broilers were randomly allotted to 5 groups with 6 replicates per group and 5 broilers per replicate. The broilers were exposed to BDE-209 concentrations with 0,0.004,0.04,0.4,4.0 g·kg-1 added to a standard diet for 42 days,respectively. At the end of the experiment,the concentration of blood urea nitrogen(BUN) and creatinine(CRE) in serum as well as kidney oxidative stress indexes were measured,and the histological and morphological structure and mitochondrial membrane potential of kidney were observed. The expression of autophagy proteins involving in p62,microtubule-associated protein 1 light chain 3(LC3) and PTEN-inducible kinase 1(PINK1)/Parkin signaling pathway were analyzed by fluorescence immunohistochemistry,real-time PCR and western blot. [Results] Compared with control,kidney injury was observed at different BDE-209 treatment groups,including glomerular enlargement and cellular composition increased,renal tubular edema and cytoplasmic porosity and mitochondrial membrane potential decreased in kidney. Additionally,the levels of BUN,CRE in serum increased significantly(P<0.05) when the content of BDE-209 was upper 0.04 g·kg-1,and the activities of SOD and GSH-Px in 0.4 and 4.0 g·kg-1 BDE-209 groups decreased significantly(P<0.05),the concentration of MDA increased in 0.04,0.4 and 4.0 g·kg-1 BDE-209 groups(P<0.05). Moreover,the expression level of p62 and the ratio of LC3-â…¡/LC3-â…  increased(P<0.05),and the PINK1 expression were also significantly up-regulated in kidney tissues(P<0.05). [Conclusions] BDE-209 exposure can cause kidney damage,and the underlying mechanisms may be that BDE-209 exacerbate oxidative stress,then activate PINK1/Parkin pathway to induce mitochondrial injury,promote the transformation of autophagy protein LC3-â…  to LC3-â…¡ and the accumulation of p62 protein,which hindere the degradation of autophagy and resulted in the renal injury. 参考文献/References: [Objectives] The aim of this study was to investigate the effects of decabromodiphenyl ether(BDE-209) exposed to broilers on kidney damage,and to explore the potential nephrotoxicity and mechanisms. [Methods] One day-old 150 male AA broilers were randomly allotted to 5 groups with 6 replicates per group and 5 broilers per replicate. The broilers were exposed to BDE-209 concentrations with 0,0.004,0.04,0.4,4.0 g·kg-1 added to a standard diet for 42 days,respectively. At the end of the experiment,the concentration of blood urea nitrogen(BUN) and creatinine(CRE) in serum as well as kidney oxidative stress indexes were measured,and the histological and morphological structure and mitochondrial membrane potential of kidney were observed. The expression of autophagy proteins involving in p62,microtubule-associated protein 1 light chain 3(LC3) and PTEN-inducible kinase 1(PINK1)/Parkin signaling pathway were analyzed by fluorescence immunohistochemistry,real-time PCR and western blot. [Results] Compared with control,kidney injury was observed at different BDE-209 treatment groups,including glomerular enlargement and cellular composition increased,renal tubular edema and cytoplasmic porosity and mitochondrial membrane potential decreased in kidney. Additionally,the levels of BUN,CRE in serum increased significantly(P<0.05) when the content of BDE-209 was upper 0.04 g·kg-1,and the activities of SOD and GSH-Px in 0.4 and 4.0 g·kg-1 BDE-209 groups decreased significantly(P<0.05),the concentration of MDA increased in 0.04,0.4 and 4.0 g·kg-1 BDE-209 groups(P<0.05). Moreover,the expression level of p62 and the ratio of LC3-Ⅱ/LC3-Ⅰ increased(P<0.05),and the PINK1 expression were also significantly up-regulated in kidney tissues(P<0.05). [Conclusions] BDE-209 exposure can cause kidney damage,and the underlying mechanisms may be that BDE-209 exacerbate oxidative stress,then activate PINK1/Parkin pathway to induce mitochondrial injury,promote the transformation of autophagy protein LC3-Ⅰ to LC3-Ⅱ and the accumulation of p62 protein,which hindere the degradation of autophagy and resulted in the renal injury. 参考文献/References: [ABSTRACT FROM AUTHOR]