Therapeutic Effects Of Shenwei Decotion On Chronic Kidney Disease In Male Rats

Objective: To create animal model of chronic kidney disease of the immune and metabolic complex pathogenesis by combining with adriamycin and adenine, which lead to both glomerular and tubular damage.The proteinuria, serum creatinine, blood urea nitrogen and renal fibrosis of model rats were observed in this study to research the effect of Shenwei Decotion. Meanwhile, we explored the therapeutic effects of Shenwei Decotion on chronic kidney disease and provided scientific basis for its clinical application. Methods: ①Experimental animal: Clinically healthy 240 male Sprague-Dawley rats(250-300 g weight) provided by SPF experimental research center of Sichuan Medical College were used in this experiment.②Making the model: The rats were divided randomly into six groups each containing 20 animals, which are normal group(N), adriamycin group(A),adenine group(B), low-dose model group(AB1), middle-dose model group(AB2), high-dose model group(AB3). Before starting the experiment, the rats were acclimatized in experimental environment for 7 days. The four groups(A,AB1, AB2 and AB3) were intravenously injected with different doses of adriamycin(followed by 7.5mg/kg, 2.5mg/kg, 5mg/kg, 7.5mg/kg). The other four groups(B, AB1, AB2 and AB3) received adenine 200 mg/kg/d by gavage daily. Meanwhile, The rats of N group received equal volume of normal saline via caudal vein injection and by gavage. The molding cycle was 1 month.③Different drug intervention: The animals were divided into six groups, which are normal group, model group, Valsartan group, low-dose Shenwei Decotion group, middle-dose Shenwei Decotion group, high-dose Shenwei Decotion group. Except the normal group, other groups were in accordance with the above method to establish the model. After model establishment, the animals received different drug intervention. The 3 groups(low-dose Shenwei Decotion group, middle-dose Shenwei Decotion group, high-dose Shenwei Decotion group) were fed different doses of Shenwei Decotion by gavage. Valsartan group were fed the equivalent human dose of valsartan. The normal group and model group were given the same volume of normal saline. At the end of the second, 4th and 6th week after modeling, the urine, blood tissue samples of rats were collected to detect and analyze. Results: ①All the rats’ weight of 5groups(A, B, AB1-3) declined after modeling, which had a significant difference compared with the normal group(P<0.01). The weight of model groups rats decreased significantly more than the control groups(P<0.05).②The 24 h urine protein of rats in each group was increased more than the normal group(P<0.05). Compared with control groups(A and B), the urine protein of rats in 2 groups(AB2 and AB3) has a significant difference(P<0.01).③The levels of serum creatinine, blood urea nitrogen in groups(AB2and AB3) were higher than control group(A, B) since the end of 2th week(P<0.01). Meanwhile, this experiment turned out that model group AB2 was the most suitable dose group.④The levels of 24-hour urine protein in Shenwei Decotion groups and Valsartan group were lower than the one in model group(P<0.05). The levels of 24-hour urine protein in Shenwei Decotion groups significantly decreased, the difference between Shenwei Decotion groups and Valsartan group was statistically significant(P<0.05).⑤Compared with model group, The levels of serum creatinine, blood urea nitrogen in Shenwei Decotion groups significantly decreased,while in groups(middle-dose Shenwei Decotion group, high-dose Shenwei Decotion group) was lower than low-dose Shenwei Decotion group(P<0.05). Meanwhile, there was no significant difference in Scr,BUN level between Valsartan group and model group(P>0.05). ⑥ Shenwei Decotion groups and Valsartan group can reduce the expression of TGF-β1 in renal tissue, compared with the model group was statistically significant(P<0.05), and 2 groups(middle-dose Shenwei Decotion group, high-dose Shenwei Decotion group) reduced more significantly. Conclusion:①Based on the classical model, we could successfully create animal model of chronic kidney disease with glomerular and tubular damage. ② Shenwei Decotion as well as ARB drugs could significantly reduce the proteinuria in CKD rats, also could reduce the levels of serum creatinine, blood urea nitrogen in rats to protect renal function. While its specific mechanism remains to be further research. ③ Shenwei Decotion could reduce the expression of TGF-β1 in renal tissue to intervene in the renal fibrosis and delay the process of chronic kidney disease, thereby protecting renal function.