The Protective Effect Of Compound Shenhua Tablet On Rats With Adriamycin Nephropathy And The Underlying Mechanism

Objective:The injury of the slit diaphragm protein of the glomerular podocyte and the cytoskeleton of the podocyte injury is closely related to the occurrence of proteinuria. This study used an adriamycin-induced nephropathy model to investigate the renal therapuetic effect and mechanism of Compound Shenhua Tablet on rats with adriamycin-induced. Inhibition of renin-angiotensin-aldosterone system (RAS) can reduce proteinuria. This study also investigate the renal therapuetic effect and mechanism of irbesartan on model above.Methods:Exp.1 The experimental animals were divided into control group, model group, methylprednisolone(MP) group, astragaloside group, SHT low-dose group, SHT middle-dose group and SHT high-dose group. The 24-h urinary protein excretion and biochemical indicators were quantitatively determined, and kidney tissues were collected so that pathological changes of the kidneys could be examined using light microscopy and electron microscopy. The mRNA and protein expression of nephrin, podocin, CD2-associated protein, and desmin in the kidney tissue of the rats were analyzed. Exp.2 The experimental animals were divided into control, model, methylprednisolone, and irbesartan groups. The methods of Exp.1 and Exp.2 are the same.Results:Exp.1 At two weeks after modeling, the levels of urinary protein excretion of rats in all other groups (exception of the control group) were more than 50mg/24h, suggesting that the model was successful. At eight weeks after drug intervention, the level of urinary protein excretion of the rats in the middle and high-dose of SHT groups were lower than that of the model group (P<0.05). At the end of 12 weeks of drug intervention, the urine protein of model group increased significantly compared with the control group (P<0.01). Urinary protein was lower in the MP group, astragaloside group, low, middle and high-dose of SHT groups than in the model group. The difference was statistically significant and the difference in middle and high-dose of SHT groups were more obvious (P<0.01), but the lower the degree of proteinuria is lower than MP group, higher than that of astragaloside group. Electron microscopy showed that the majority of the glomerular foot processes of the rats in the model group were fused and disappeared, the foot processes of MP group were nearly normal, and the fusion of the foot processes in the astragaloside group, low, middle and high-dose of SHT groups were significantly reduced. Compared with the control group, the mRNA and protein expression levels of nephrin and podocin in the renal tissue of the rats in the model group were down-regulated (P<0.01), whereas the mRNA and protein expression levels of CD2AP and desmin were up-regulated (P<0.01). The mRNA and protein expression levels of nephrin and podocin in the MP group, astragaloside group, low, middle and high-dose of SHT groups were up-regulated compared with the model group (P<0.05), whereas the mRNA and protein expression levels of CD2AP and desmin were significantly down-regulated (P<0.01). Exp.2 At the end of 12 weeks of drug intervention, the urinary protein excretion levels of the rats in the MP and irbesartan groups were lower than that in the model group (P<0.01). Electron microscopy showed that fusion of the glomerular foot processes in the irbesartan group was significantly reduced. The mRNA and protein expression levels of nephrin and podocin in the irbesartan groups was up-regulated compared with the model group (P<0.05), whereas the levels of CD2AP and desmin were significantly down-regulated (P<0.01).Conclusions:Compound Shenhua Tablet can significantly decrease the level of proteinuria in rats with adriamycin nephropathy, increase serum albumin, better than astragaloside, showing a better time and dose effect; Irbesartan also showed the same curative effect, the level of proteinuria decreased significantly. As a possible mechanism, Compound Shenhua Tablet and irbesartan may improve the slit diaphragm protein of the glomerular podocyte and stabilize the cytoskeleton of the podocyte, thereby promoting the repair of the injury in the glomerular podocytes.