Study On The Therapeutic Effect And Mechanism Of Qufengzhitongsan On Drug-induced Renal Injury

Objective:Drug-induced kidney injury is a common clinical complication of drugs,and the incidence is increasing year by year.This experiment studies the therapeutic effect and mechanism of QFZTS on cisplatin-induced renal injury and contrast-induced nephropathy in rats,and provides new targeted sites and treatment methods for clinical treatment of cisplatin-induced renal injury and contrast-induced nephropathy.Methods:1.Study on the therapeutic effect and mechanism of QFZTS on cisplatin-induced renal injury rat model.Normal control group:d1 was injected intraperitoneally with sodium chloride injection at a dose of 7.5ml·kg^-1.From d2to d10,1 m L·100g^-1purified water was given to the stomach once a day.Cisplatin renal injury model group:d1 intraperitoneal injection of a single dose of cisplatin 7.5 mg·kg^-1.From d2 to d10,1 m L·100g^-1purified water was given to the stomach once a day.QFZTS high-dose and low-dose groups:d1intraperitoneal injection of a single dose of cisplatin 7.5 mg·kg^-1.From d2 to d10,the drugs were given by intragastric administration in a volume of1m L·100g^-1every day,and the QFZTS suspension was given at the dose of 1.6g·kg^-1in the low-dose group and 3.2g·kg^-1in the high-dose group.Positive control group:Amifostine was pretreated before administration of d1 cisplatin,administered intraperitoneally at a dose of 200 mg·kg^-1,and 30 minutes later,a single dose of cisplatin was injected intraperitoneally with 7.5 mg·kg^-1.From d2to d10,1 m L·100g^-1purified water was given to the stomach once a day.On d11,the rats were sacrificed to collect blood from the abdominal artery and kidney samples were collected.Detect the levels of SCr,BUN,SOD,MDA,IL-1β,NF-κB,TNF-α,NGAL,KIM-1 in serum;observe kidney tissue sections under microscope to compare the pathological changes of samples in each group;detect rat kidneys by PCR The expression of PI3K,AKT,and Caspase-3 genes in tissues.2.Study on the therapeutic effect and mechanism of QFZTS on the rat model of contrast medium nephropathy.Normal control group:d1 was injected with sodium chloride injection into the tail vein at a dose of 7.5ml·kg^-1.From d2 to d10,1 m L·100g^-1purified water was given to the stomach once a day.Contrast nephropathy model group:d1 was given INDO at a dose of 10mg·kg^-1by gavage,and then L-NAME 10mg·kg^-1was injected into the tail vein,and after30 minutes,76%was injected into the tail vein at a dosage of 10ml·kg^-1Compound diatrizoate meglumine injection.From d2 to d10,1 m L·100g^-1purified water was given to the stomach once a day.QFZTS low-dose group and high-dose group:d1 was modeled in the same way as the model group.From d2to d10,the drugs were given by intragastric administration in a volume of1m L·100g^-1every day,and the QFZTS suspension was given at the dose of 1.6g·kg^-1in the low-dose group and 3.2g·kg^-1in the high-dose group.Positive control group:d1 was modeled in the same way as the model group.From d2 to d10,1m L·100g^-1was given by gavage once a day,and NAC solution（250mg/kg）was given.On d11,the rats were sacrificed to collect blood from the abdominal artery and kidney samples were collected.The serum levels of SCr,BUN,SOD,MDA,IL-1β,NF-κB,TNF-α,NGAL,KIM-1 were detected;the expression of PI3K,AKT,and Caspase-3 genes in rat kidney tissues was detected by PCR.Results:QFZTS can effectively reduce the contents of SCr,BUN,NGAL,KIM-1,MDA,NF-κB,IL-1β,and TNF-αin rats with cisplatin-induced renal injury and contrast-induced nephropathy;Increase the level of SOD in the serum;up-regulate PI3K and AKT in the kidney tissue to inhibit the expression of Caspase-3 m RNA;reduce the inflammatory response,reduce the rate of apoptosis,relieve tubular dilatation and interstitial fibrosis,and protect renal function.Conclusion:QFZTS has a therapeutic effect on renal damage in rats with cisplatin-induced renal injury and contrast-induced nephropathy,and its mechanism may play an anti-apoptotic effect by up-regulating the expression of key molecular genes in the PI3K/AKT signaling pathway and reducing IL-1β,NF-κB,TNF-αand other inflammatory factors are released,inhibiting the apoptosis of Caspase-3 and delaying the process of inflammation,which may also be related to the down-regulation of the body’s oxidative stress state.