##Establishment of DM and DN animal models
We induced diabetes models according to the protocols of Animal Models of Diabetic Complications Consortium. Sprague-Dawley rats weighing 160–180 g were induced to diabetes with a single 60 mg/kg intraperitoneal injection of freshly prepared STZ (Figure 1A). The DN-SRS group was then treated with intraperitoneal injection of SRS 16-86 at a dose of 15 mg/kg once/day from week 1 to week 8 after STZ treatment, while the DN group was treated with the same dose of dimethylsulfoxide (DMSO) (Figure 1A). Blood glucose in the DN and DN-SRS groups was significantly higher than that in the control group 3 days after STZ treatment; moreover, both the DN and DN-SRS groups’ body weight was significantly lower than that in the control group, proving that the diabetic animal model was successfully constructed (Figure 1B,1C). We evaluated renal function changes by measuring 24-hour urine volume, creatinine (CRE2U), and urine total protein (UTP). As shown in Figure 2, 24-hour urine volume and the content of CRE2U and UTP in the DN and DN-SRS groups were markedly higher than those of control group at the 8-week time point, indicating that the DN animal model was successfully constructed (Figure 2A,2B,2C).