Expression and clinical significance of Beclin-1,Bcl-2,and Bax in renal cells of rats with exprimental fluorosis

Objective To observe expressions of autophagy-related gene Beclin-1,apoptosis-related gene Bcl-2,and Bax in renal cells of rats with fluorosis and to explore the significance of the exprssions in renal injury associated with chronic fluorosis.Methods Twenty-four healthy Sprague-Dawley rats were randomly divided into a control group (8 rats with fluoride<0.5 mg/L in drinking water),a low fluoride group (8 rats with fluoride of 50 mg/L in drinking water)and a high fluoride group (8 rats with fluoride of 100 mg/L in drinking water).All the rats were sacrificed at 9-month of the treatment.The occurrence of dental fluorosis in the rats was observed.The fluoride content in urine and bone was determined using fluoride ion selective electrode method.Pathological changes in renal tissues were observed with optical microscopy.The protein expressions of Beclin-1,Bcl-2,Bax in renal tissues were determined with immunohistochemistry and the expression of Beclin-1 mRNA was analyzed with in situ hybridization.Results The detection rate of dental fluorosis was 75%(6/8)and 100%(8/8)for the rats of low and high fluoride group and the fluoride contents in urine were 10.09±0.88 mg/L and 18.09±0.89 mg/L and those in bone were 5 500.84±1 093.47 μg /g and 7 477.94±1 315.88 μg/g for the rats of low and high fluoride group,which were significantly higher compared to those of the rats of control group (all P < 0.05).The edema of tubular epithelial cells and obvious intersitial congestion of renal tubules were observed with light microscopy in the rats with fluoride exposure and these pathogenic changes aggravated with the increase of fluoride concentration.The expressions of Beclin-1 (168.90±8.68 and 146.32±10.02)and Bax (153.74±10.56 and 134.29±9.85)in renal tissues of the rats with low and high fluoride exposure were significantly lower than those of the rats of the control group (all P < 0.05),while the expression of Bcl-2 (167.64±7.51 and 185.32±8.55) in renal tissues of the rats of low and high fluoride group was significantly higher than that in the rats of the control group (both P < 0.05).Meanwhile the Beclin-1 mRNA expression (166.94±13.21 and 146.11±17.66)in renal tissues of the rats of low and high fluoride group decreased significantly compared to that of the rats of the control group (both P < 0.05).Conclusion Chronic fluorosis can induce autophagy and apoptosis of renal tubular epithelial cells in rats and the autophagy and apoptosis may be involved in the pathogenesis of kidney injury in chronic fluorosis.