The Protective Effect and MoA of Panax notoginseng Saponins Combined with Aminoguanidine on Kidney in Diabetic Nephropathy Rats
Guangfu Lv, Zhikai Qiu, Hongbo Ye, Chao Ma, Shizhuo Chang and Zhe Lin
Research and Development Center TCM Pharmacology laboratory, Changchun University of Chinese Medicine, Changchun 130117, China
College of Pharmacy, Changchun University of Chinese Medicine 130117, Changchun, China
Abstract: This study was conducted to explore the protecting effect and treatment mechanism of Panax notoginseng saponins (PNS) in combination with aminoguanidine (AG) on kidney functions in diabetic nephropathy (DN) rats. Rats were divided into 5 groups (A, P, P+A, D and N) and diabetes was induced by streptozotocin (STZ). After 8 weeks, all rats were sacrificed and the renal functions as well as 24 hrs urinary proteins were examined quantitatively. Periodic acid-Schiff stain (PAS) was used to observe the pathological changes of renal tissue. Immune-nephelometry, immunoradiometric assay, Immunohistochemical and real-time fluorescence were used for blood C-reactive protein, tumor necrosis factor-α (TNF-α), surface specific marker antigen (ED-1) and determination of transforming growth factor- β1 (TGF-β1) in kidney tissue. There was a significant reduction in renal pathological changes of rats in group P, A, and P+A when compared with group D, while the changes were most obvious in group P+A. Blood glucose, glomerular volume (V), serum creatinine, 24 hrs urinary protein, blood CRP and TNF- in groups P, A and P+A were significantly (P<0.05) lower than group D with lowest in group P+A. Immunohistochemical staining showed, only a few ED-1 positive staining (macrophages) in group N glomeruli and the renal tubules. The staining of ED-1 group D was higher while in groups P, A and P+A was significantly reduced. There was a basic quantity of TGF-β1 mRNA expression in group N rats while the expression of TGF-β1 mRNA in group D was significantly increased when compared with control group. In group P, A and P+A, the expression level of TGF-β1 mRNA was significantly (P<0.05) decreased. The protective effect of combined use of these two PNS and AG on the kidney is superior to the single drug treatment. The mechanism of PNS combined with AG in the treatment of DN may be closely related to the reduction of urinary protein, anti-inflammatory response, and inhibition of the expression of TGF-β1.