10-HDA对急性氯化镉所致肾损伤的保护作用及自噬相关蛋白表达的影响OA

[Background]Acute cadmium(Cd)exposure can cause damage to multiple tissues,with the kidney being the primary target organ.The development of Cd-induced acute kidney injury involves complex mechanisms,in which autophagy and oxidative stress play crucial roles. [Objective]To investigate the effect of 10-hydroxy-2-decenoic acid(10-HAD)on kidney injury in mice exposed to cadmium,and provide experimental basis for studying the pathogenesis and prevention of Cd poisoning. [Methods]Thirty-five male C57BL/6 mice were divided into 7 groups(each of 5 mice):control group(normal saline,intraperitoneal injection),CdCl2 group(4 mg·kg-1,intraperitoneal injection),intervention groups(4 mg·kg-1 CdCl2,intraperitoneal Injection +50,100,150,or 200 mg·kg-110-HAD,oral gavage),and 10-HAD group(150 mg·kg-1,oral gavage).All treatments were given for 14 d.Twenty-four hours after the last infection,physiological indicators[blood urea nitrogen(BUN),creatinine(CRE),malondialdehyde(MDA),and superoxide dismutase(SOD)],histopathological indicators,autophagy-related proteins(Atg7,Atg5,Beclin-1,and LC3),and mitochondrial autophagy-related proteins(PINK1 and Parkin)were detected to examine the effect of 10-HAD on kidney injury caused by CdCl2. [Results]Compared with the control group,the body weight of mice in the CdCl2 group was significantly reduced(P<0.01);compared with the CdCl2 group,the body weight of mice after intervention with different concentrations of 10-HAD was significantly increased(P<0.01).CdCl2 significantly increased BUN and CRE in the serum samples compared with the control group(P<0.01),which was signifi-cantly reduced to varying degrees after 100,150,and 200 mg·kg-110-HAD intervention(P<0.01).MDA significantly increased and SOD significantly decreased in the renal cortex following CdCl2 administration compared with the control group(P<0.01),which was resolved following 10-HAD administration at different concentrations(P<0.01).In histopathological studies,10-HAD restored injured kidney tissues induced by CdCl2.The expression levels of autophagy proteins Atg7 and LC3-Ⅱ/Ⅰ were significantly increased(P<0.05),and the expression level of Beclin-1 was significantly decreased(P<0.05)in the CdCl2 group compared with the control group.The expression levels of Atg7 were reduced to varying degrees after treatment with designed concentrations of 10-HAD,the expression levels of LC3-Ⅱ/Ⅰ were also re-duced in the 50,150,and 200 mg·kg-110-HAD intervention groups,and the expression levels of Beclin-1 were increased in the 50,100,and 150 mg·kg-110-HAD intervention groups(P<0.05).The expression levels of PINK1 and Parkin in the CdCl2 group and the 50 mg·kg-110-HAD intervention group were lower than those in the control group(P<0.01).Compared with the CdCl2 group,the expression levels of PINK1 increased to varying degrees after 100,150,and 200 mg·kg-110-HAD intervention,and the expression levels of Parkin increased in all 10-HAD intervention groups(P<0.01). [Conclusion]The intervention using 10-HAD can lessen acute kidney injury caused by CdCl2,reduce the expression of autophagy-related proteins,and increase the expression of mitochondrial autophagy-related proteins.