Qingrexiaozheng formula (QRXZF) has been shown to be effective in improving kidney injury in diabetic kidney disease (DKD) , but the mechanism remains to be unclear.

To explore the effect and mechanism of action of QRXZF in the improvement of kidney injury induced by unilateral nephritic resection combined with streptozotocin (STZ) in DKD rats.

The experiment was implemented from July to November, 2019. Thirty healthy SPF male SD rats were randomly divided into sham operation group (NC group, n=10) and model group (n=20) . Rats in NC group received 1 cm transverse incision performed at the body surface anatomical position of the right kidney and sutured, and intraperitoneal injection of citric acid buffer when the wound healed one week later. Those in model group were treated with right nephrectomy, and received a single intraperitoneal injection of STZ solution (55 mg/kg) with the same volume as the citric acid buffer for the NC group one week later to establish the DKD model. Then rats in the model group were randomly divided into DKD subgroup (n=10) and QRXZF subgroup (n=10) when the modeling was successfully achieved. After this, rats in NC group and DKD subgroup received intragastric administration of the same amount (1 ml/100 g) of 0.9% sodium chloride solution once a day, and those in QRXZF subgroup received intragastric administration of QRXZF at a dose of 7.92 g·kg^-1·d^-1. During the intervention, weight was measured every week. After 16 weeks of intervention, a 24-hour urine, serum and kidney tissue specimens were collected, kidney weight was measured, and the kidney weight index was calculated. Enzyme-linked immunosorbent assay was used to detect the microalbumin in 24-hour urine (24 hUpro) . The automatic biochemical analyzer was used to analyze serum creatinine (Scr) , blood urea nitrogen (BUN) and serum albumin (ALB) . Hematoxylin-eosin staining, Periodic Acid-Schiff staining and Masson's trichrome staining were performed to observe the damage degree of kidney tissue. Immunohistochemical method was used to detect the expression level of Caspase-3 and p16 in kidney tissue. The apoptosis of renal tubular cells was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling.

Compared with rats in the NC group, those in DKD and QRXZF subgroups had lower weight and higher kidney weight index (P<0.01) . Rats in QRXZF subgroup had higher weight and lower kidney weight index than those in DKD subgroup (P<0.01) . In comparison to rats in the NC group, rats in DKD subgroup had higher levels of 24 hUpro, Scr and BUN lower level of ALB (P<0.01) , and those in QRXZF subgroup had higher levels of 24 hUpro and BUN, and lower level of ALB (P<0.01) . Rats in QRXZF subgroup had higher levels of 24 hUpro, Scr and BUN, and lower level of ALB than did those in DKD subgroup (P<0.01) . Compared with rats in the NC group, obvious pathological injury, glomerular hypertrophy and interstitial tubular fibrosis were observed in kidney tissues in rats of both DKD and QRXZF subgroups, but the degree of pathological changes was much lighter in QRXZF subgroup. Immunohistochemistry analysis showed that the expression levels of P16 and Caspase-3 in renal tissue in DKD or QRXZF subgroup were higher than those in NC group (P<0.01) . The expression levels of P16 and Caspase-3 in renal tissue in QRXZF subgroup were lower than those in DKD subgroup (P<0.01) . The rate of renal tubular cell apoptosis in DKD or QRXZF subgroup was higher than that in NC group (P<0.01) . The rate of renal tubular cell apoptosis in QRXZF subgroup was lower than that in DKD subgroup (P<0.01) .

QRXZF effectively improved the renal function, attenuate the pathological damage and fibrosis of the kidney, inhibit the expression of Caspase-3 and p16 in renal tissues, and decrease the rate of renal tubular cell apoptosis in DKD rats, suggesting that the mechanism of QRXZF in improving kidney may be related to inhibiting the aging and apoptosis of kidney cells.