| Objective: To observe the pharmacological effects of Compound Shelong Capsule on reducing proteinuria in rats with adriamycin-induced nephropathy and its effects on podocyte-associated molecules Nephrin,?3?1integrin and ?-actinin-4,and to explore the mechanism of Compound Shelong Capsule on proteinuria in molecular biology.Methods: Sixteen of 120 healthy male SD rats were randomly selected as blank control group.The remaining rats were injected with adriamycin twice in tail vein to establish renal proteinuria model.Each rat was injected with adriamycin 4mg·kg-1 for the first time in tail vein,and 2mg·kg-1for the second time one week later.After successful modeling,rats were divided into model control group,high-dose group,medium-dose group,low-dose group and Tripterygium wilfordii polyglycoside group.After 8 weeks of observation,24-hour urinary protein content was measured at the 4th,6th and 8th weekends,serum albumin,creatinine,urea nitrogen,total cholesterol,triglyceride and low-density lipoprotein were measured at the 4th and 8th weekends.At the 8th weekend,HE staining was used to detect rat kidney pathology,immunoblotting was used to detect the expression of podocyte-related proteins Nephrin,?3?1integrin and ?-actinin-4 in rat kidney,and Real Time PCR was used to detect the expression of Nephrin m RNA,?3?1integrin m RNA and?-actinin-4 m RNA in rat kidney.Results:1.Compound Shelong Capsule can improve the general state of diet,drinking water,body weight,fur and activity in rats with adriamycin nephropathy;2.At the end of the 4th,6th and 8th week,the 24-hour urinary protein content of each group was significantly lower than that of the model group(P < 0.01).3.At the 4th and 8th weekend,compared with the model group,Compound Shelong Capsule and Tripterygium Wilfordii Polyglycoside Tablets could significantly increase serum albumin(P < 0.01),reduce serum creatinine,urea nitrogen,total cholesterol,triglyceride and low density lipoprotein(P < 0.05).4.Compound Shelong Capsule can improve the renal pathological status of adriamycin nephropathy rats,reduce mesangial cells and matrix proliferation,tubular epithelial cell necrosis and renal interstitial inflammatory cell infiltration.5.Immunoblotting showed that the expression of Nephrin and ?3?1integrin protein in kidney tissues of each group was higher than that of model group(P < 0.05),and the expression of ?-actinin-4 protein in kidney tissues was significantly lower than that of model group(P < 0.05).6.Real Time PCR showed that the expression of Nephrin m RNA and?3/?1integrin m RNA in kidney tissues was up-regulated(P < 0.05)and the expression of?-actinin-4 m RNA protein in kidney tissues was down-regulated(P < 0.05)compared with the model group.Conclusion:1.Compound Shelong Capsule can reduce 24-hour proteinuria excretion in adriamycin nephropathy rats.2.Compound Shelong Capsule can increase serum ALB value,decrease serum SCr and BUN value,and decrease serum TC,TG and LDL-C value in adriamycin nephropathy rats.3.Compound Shelong Capsule may repair damaged podocytes from multiple sites by up-regulating the expression of Nephrin protein and Nephrin m RNA,up-regulating the expression of ?3?1integrin protein and up-regulating the expression of ?3/?1integrin m RNA,down-regulating the expression of ?-actinin-4 protein and ?-actinin-4 m RNA,and maintaining the integrity of podocyte structure and function,thus reducing the excretion of proteinuria in rats with adriamycin nephropathy. |
PDF Full Text Request