Abstract: Objective To investigate the effect of ginsenoside Rh2 (G-Rh2) on renal fibrosis and cell apoptosis in rats with diabetic nephropathy (DN) and explore its possible mechanism. Methods Thirty male SD rats were randomized equally into control group, DN group and ginsenoside Rh2 intervention group. In the latter two groups, rat models of DN were established by intraperitoneal injection of streptozotocin, and the rats in the control group received injection of citrate buffer. After successful modeling, the rats in ginsenoside Rh2 intervention group were given ginsenoside Rh2 (20 mg · kg- 1) intragastrically on a daily basis for 12 weeks, and those in the other two groups were treated with normal saline. After the treatments, the histological changes of the kidneys of the rats were observed using HE staining and PAS staining, and renal fibrosis was assessed using Masson staining; TUNEL staining was used to observe cell apoptosis in the kidney tissue. Western blotting was performed to detect renal expressions of collagen I, collagen III, cleaved caspase-3, Bcl-2, and DDR1; the localization of DDR1 expression in the kidney tissue was determined using immunohistochemistry. Results Compared with the control rats, the rat models of DN showed obvious renal fibrosis with an increased apoptosis index in the kidneys (P<0.01), where the expressions of collagen I, collagen III, cleaved caspase-3, and DDR1 were all upregulated (P<0.01) and Bcl-2 expression was down-regulated (P<0.01). Treatment with ginsenoside Rh2 significantly reduced the severity of renal fibrosis, lowered the apoptosis index, decreased the expression levels of collagen I, collagen III, cleaved caspase-3, and DDR1 (P<0.05 or P<0.01), and increased the expression of Bcl-2 in the kidney of rats with DN (P<0.05). Conclusion Ginsenoside Rh2 inhibits renal fibrosis and renal cell apoptosis possibly in association with the down-regulation of DDR1 expression in the kidney of rat models of DN.

Key words: diabetic nephropathy, ginsenoside Rh2, discoid domain receptor 1, renal fibrosis, apoptosis