OBJECTIVE

2

To investigate the mechanism of Shilinqing granules preventing the formation of calcium oxalate kidney stones in rats.

METHODS

2

Sixty rats were randomly divided into blank group， model group， Shilingqing granules low-dose， medium-dose and high-dose groups （6.5， 13， 26 g/kg）， SIRT3 inhibitor group （Shilingqing granules 26 g/kg+SIRT3 inhibitor 25 mg/kg）， with 10 rats in each group. Except for blank group， other groups were given 1% ethylene glycol solution instead of drinking water， and intragastrical administration of 2% ammonium chloride solution 2 mL， for 4 consecutive weeks， to induce kidney stones rat model； at the same time， administration groups were given relevant medicine intrgastrically， blank group and model group were given constant volume of normal saline intrgastrically. The 24 h urine volume， urine pH， urine contents of Ca

2+

and oxalic acid （Ox）， serum contents of creatinine （Cr）， blood urea nitrogen （BUN） and Ca

2+

were all determined； the renal histopathology， calcium oxalate crystallization and ultrastructure were observed； the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， reactive oxygen species （ROS） and osteopontin （OPN） in renal tissue of rats were determined； mRNA and protein expressions of SIRT3， FOXO3a， and SOD2 in renal tissue of rats were determined.

RESULTS

2

Compared with blank group， 24 h urine volume， urine pH， SOD level， mRNA and protein expressions of SIRT3， FOXO3a and SOD2 in renal tissue were decreased significantly in model group （

P

＜0.05 or

P

＜0.01）. The contents of urine Ca

2+

and Ox， serum contents of Cr， BUN and Ca

2+

and the levels of ROS， MDA and OPN in renal tissue were increased significantly （

P

＜0.01）. The pathological damage of renal tissue was severe， with a large number of diffuse black crystals， thickened glomerular basement membrane， and mitochondrial edema in podocytes and renal tubular epithelial cells. Compared with model group， the above indexes （except for serum content of Ca

2+

in low-dose group） were significantly reversed in Shilinqing granules groups （

P

＜0.05 or

P

＜0.01）； pathological renal damage， calcium crystal， mitochondrial damage of glomerular podocyte and renal tubular epithelial cell were significantly improved； there was no statistical significance in the changes of above indexes in SIRT3 inhibitor group （

P

＞0.05）.

CONCLUSIONS

2

Shilinqing granules can effectively inhibit the formation of calcium oxalate kidney stones in rats and improve renal damage， the mechanism of which may be related to the improvement of anti-oxidant effect and the activation of SIRT3/FOXO3a signaling pathway.