BACKGROUND:Cordyceps polysaccharide is a commonly used adjuvant drug for clinical treatment of nephrotic syndrome. As a classic model of nephrotic syndrome induced by adriamycin, the Sprague-Dawley rat model of nephrotic syndrome exhibits similar clinical manifestations and pathological changes to minimal-change nephropathy in humans. OBJECTIVE:To observe the effect of adipose-derived mesenchymal stem cel s (ADMSCs) transplantation combined with cordyceps polysaccharide on renal function and hypercoagulable state in rats with nephrotic syndrome. METHODS:ADMSCs suspension was made in vitro and labeled using PKH26. Fifty Sprague-Dawley rats were randomized into normal (no intervention), model, ADMSCs, cordyceps polysaccharide and combined treatment groups (n=10/group). Adriamycin administration was performed to make rat models of nephrotic syndrome in the latter three groups. After modeling, model rats were respectively given no treatment, ADMSCs intravenously for 3 days, cordyceps polysaccharide intragastrical y for 12 weeks, or their combined use. Then, 24-hour urinary protein, serum total cholesterol, triglyceride, total protein, albumin, high-density lipoprotein, low-density lipoprotein, creatinine, blood urea nitrogen levels and coagulation changes were detected at 12 weeks. Meanwhile, histopathological changes of renal tissues were observed under light microscope;survival and distribution of PKH26-labeled ADMSCs were observed by fluorescence microscopy;and expression of Hpa gene in renal tissue was detected by RT-PCR. RESULTS AND CONCLUSION:Compared with the model group, the 24-hour urinary protein, serum total cholesterol, triglyceride, low-density lipoprotein, creatinine, and blood urea nitrogen levels were significantly lower, while the serum total protein, albumin and high-density lipoprotein levels were significantly higher in the three treatment groups (P<0.05). These indicators showed significant differences between the combined group and ADMSCs and cordyceps polysaccharide groups (P<0.05). Both ADMSCs transplantation and cordyceps polysaccharide significantly relieved the hypercoagulable state of rats with nephrotic syndrome, and their combined effects were stronger (P<0.05). After treatment, the pathological improvement in the kidney tissues was found in the three treatment groups;moreover, it was better in the combined treatment group than the ADMSCs and cordyceps polysaccharide groups. Better improvement in the number of PKH26-labeled ADMSCs and the expression of Hpa mRNA was observed in the combined treatment group compared with the ADMSCs and cordyceps polysaccharide groups. In conclusion, the combination of ADMSCs transplantation and cordyceps polysaccharide can improve kidney function and hypercoagulable state in rats with nephrotic syndrome, reducing pathological damage to the kidney tissue.