Role of autophagy in kidney damage of rats caused by cadmium

Objective To explore the kidney damage in the rats caused by different concentrations of CdCl2 and the role of autophagy in the kidney damage,and to clarify the mechanism of the kindney damage caused by CdCl2.Methods 40 Wistar rats were randomly divided into blank control group,low dose group(0.2mg·kg-1 CdCl2),middle dose group(0.4mg·kg-1 CdCl2)and high dose group(0.8mg·kg-1 CdCl2),and there were 10 rats in each group.The cadmium chloride solution was administrated by intraperitoneal injection to prepare the rat models of kidney damage.The same volume of normal saline was injected into the rats in blank control goup.The general status and body weights of all rats were observed.The kidney tissue and blood of the rats were obtained 5weeks later.The renal function indexes including creatinine,blood urea nitrogen,andβ2-microglobulin were detected;the levels of cadmium in the kidney tissue of the rats in various groups were detected by atomic absorption spectrometry;the relative expression level of LC3 B and expression level of Beclin1 protein were detected by Western blotting and immunohistochemical methods,respectively.Results Obvious depression was seen in the rats in CdCl2 groups,and the body weights of the rats in high dose group were significantly lower than those in blank control group from 3weeks after exposure to cadmium(P0.05);the body weights of the rats in middle dose group and high dose group were significantly lower than those in blank control group at the end of this experiment(P0.05).The results of blood biochemical detection showed that the levels of creatinine,blood urea nitrogen,andβ2-microglobulin of the rats in middle dose group and high dose group were significantly higher than those in blank control group(P0.05),and the levels of creatinine of the rats in high dose group were significantly higher than those in low dose group(P0.05);the levels of blood urea nitrogen of the rats in middle dose group and high dose group were significantly higher than those in low dose group(P0.05).The results of atomic absorption spectrometry showed that there were a small amount of cadmium accumulation of the rats in blank control group,but a large amount of metal cadmium accumulated in the kidney tissue were seen in low,middle and high dose groups and the levels of cadmium were increased with the increasing of the exposure dose;the levels of cadmium of the rats in middle dose group and high dose group were significantly higher than those in low dose group(P0.05);the levels of cadmium of the rats in high dose group were significantly higher than those in middle dose group(P0.05).The immunohistochemistry results showed that the expression levels of Beclin1 protein in the kidney tissue of the rats in CdCl2 groups were significantly higher than those in blank control group(P0.05),and the expression levels of Beclin1 protein of the rats in middle dose group and high dose group were significantly higher than those in low dose group(P0.05);the expression levels of Beclin1 protein of the rats in high dose group were significantly higher than those in middle dose group(P0.05).The Western blotting results showed that the relative expression levels of LC3 Bprotein in the kidney tissue of the rats in CdCl2 groups were significantly higher than those in blank control group(P0.05),and the relative expression levels of LC3 Bprotein in the kidney tissue of the rats in middle dose group and high dose group were significantly higher than those in low dose group(P0.05).Conclusion At the range from 0.2to 0.8mg·kg-1,the kidney damage gets more and more serous with the increasing of the exposure dose of CdCl2,and autophagy may be one of the mechanisms.