| The harm of cadmium pollution to human health has been an important public health problem.Cadmium exposure induced injury and accumulated on the kidney.At present,the evaluation of the effect of cadmium pollution in the environment has been transferred from the large dose of acute exposure to low level long-term exposure.In this study,Sprague-Dawley(SD)rats as experimental animal,FAO and WHO under the Joint Expert Committee on food additives(JECFA)made of cadmium in food provisional tolerable monthly intake(PTMI,25μg/kg·bw)converted into daily gavage cadmium dose(0.1 mg/kg/d)for the low dose group,the average daily exposure to dietary cadmium residents in cadmium polluted areas(10μg/kg·bw)converted into daily gavage cadmium dose(1.0 mg/kg/d)high dose group,were treated with irrigation for 8 weeks,to observe the damage effect,rat renal toxicity and explore more sensitive indicators of early renal toxicity damage.And explore the possible mechanism of toxicity,in order to the actual state of the cadmium exposure that provide some references for the research of induced renal toxicity.The main content of this work includes 2 aspects as following:一、Research on the effects of long-term low level cadmium exposure on renal toxicity of rats.24 SD rats were randomly divided into 3 groups,each group of 8,male and female half,the control group(control),low dose group(0.1 mg/kg/d),high dose group(1.0 mg/kg/d).The rats in the control group were given normal saline every day,and the high and low dose groups were gavaged with CdCl2 solution every day,the volume of each 100 g body weight was 1 mL,Respectively before exposure(0 day),the 1,3,5,7,14,21,28,35,42,49,56 day to collect 24h rat’s urine,determination of cadmium content in urine;detection of 0,14,28,35,42,56 day in urine of β2-MG,RBP,Klotho,MT protein content.Blood samples were taken from 0,14,28,35,42 and 56 day to determine the level of Klotho protein in serum.At the end of exposure,the rats’kidneys were taken to determine the content of cadmium and the pathological changes were observed.The results showed that cadmium exposure group of urinary cadmium increased with prolonged exposure,urinary cadmium content in high dose group was higher than that of low dose group,the level of urinary cadmium in high dose group of male and female rats respectively in 49 day and 42 day was obviously higher than the control group(P<0.05).The(β2-MG,RBP,MT as three kinds of protein in the urine of cadmium exposure group increased with the extension of exposure time,and the increased degree of the three kinds of protein in female rats was higher than that in male rats.Klotho protein in the urine of cadmium exposure group decreased with prolonged exposure,reduce the protein levels in high dose group in the urine more than low dose group,the Klotho protein in female rats with exposure time reduction was higher than that of low dose group,but the four protein level changes compared with the control group had no obvious difference(P>0.05).Klotho protein in serum cadmium decreased with prolonged exposure,the protein level in serum of high dose group than in low dose group,high dose group of female rats in serum protein level at the end of the experiment(56 day)was significantly lower than the control group(P<0.05),male rats compared with the control group showed no obvious decrease(P>0.05).The content of cadmium in kidney of high dose group was significantly higher than that of control group and low dose group(P<0.01).Renal pathological changes were observed in control group showed that renal tubular and glomerular epithelial cells intact were no injuried;kidney injury in rats exposed to cadmium occurs mainly is in renal tubular,low dose group of male and female rats renal tubules showed slight edema,kidney group female rats of high dose damage than male rats showed more obvious occurrence of renal tubular epithelial cells edema,partial degeneration or apoptosis,glomerular atrophy,accompanied by inflammatory cell infiltration.The results indicated that:urine cadmium is the load index of long-term exposure to cadmium,rats in high dose after 49 daywas significantly increased,suggesting that high dose cadmium exposure can cause kidney damage;female rat urine cadmium as early as 42 day appeared urinary cadmium increased,renal pathological observations to further verify the high dose group than in low dose group kidney damage,female rats than male on kidney toxicity effect is obvious.It is suggested that the damage of renal tissue is caused by high dose cadmium exposure.In this paper of the dose,β2-MG,RBP,MT and Klotho four proteins of rats’ urine had no significant change,but compared to Klotho protein in serum of rats in urine were significantly different in female rats than male significantly;Klotho protein compared with the other three types of protein compared with the control group showed significant changes in serum,suggesting that the Klotho protein can be used as cadmium induced renal toxicity injury of sensitive indicators.Klotho protein as a renoprotective factor,can reduce the superoxide anion generation and lipid peroxidation,and induce superoxide dismutase(SOD)expression to reduce the oxidative stress of kidney damage,suggesting that this study researched on long-term low level cadmium induced nephrotoxicity which may be associated with oxidative stress injury.二、Effects of long-term low level cadmium exposure on antioxidant activity of rat kidney.At the end of 8 weeks on cadmium exposure,the rats’ kidney tissue was taken to detect the MDA content and SOD,GSH-Px,CAT three enzyme activity.The results showed that the MDA content of renal tissue increased with the increase of cadmium gavage dose,high dose group of MDA content was significantly higher than that of control group(P<0.05);female and male rats’ MDA content compared to the control group were increased by 66.67%and 41.47%;Antioxidant enzyme of the kidney including SOD,GSH-Px,CAT were increased with the cadmium gavage dose,the three kinds of enzyme activity of the female rats’ renal tissue ware lower than that of male rats,the GSH-Px activity was significantly lower than male rats(P<0.05).These results suggest that MDA is an important index to reflect the degree of lipid peroxidation,the MDA content of rats’kidney in high dose group increased significantly,female rats were more obvious,showing that the lipid peroxidation of renal tissue was greater,and the lipid peroxidation of renal tissue on female rats exposed to cadmium was fortiu.SOD,GSH-Px,CAT were the main protective enzyme system,the combination of three enzymes can remove reactive oxygen species and protect the tissues from freeradicaldamage.Compared with the control group,The activities of antioxidant enzymes SOD,GSH-Px,CAT in the exposed group were lower,showing that oxidative damage was observed in the kidney of long-term low level cadmium exposure,and the oxidative damage was more obvious in female rats.The results of this study indicate that simulated dose of dietary cadmium exposure will produce toxic effects on the body kidney,kidney injury in female rats showed obvious toxicity,mechanism of toxicity may be still associated with oxidative damage;The Klotho protein,which has protective effect on the kidney,is more sensitive to the changes of renal injury in comparison with the commonly used indicators,which provides the possibility for early monitoring of cadmium induced nephrotoxicity. |
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