Abstract: Objective: To investigate the improvement effect of Shenyuan Granule on the vascular calcification in the db/db diabetic nephropathy (DN) mice induced by high phosphorus and its possible mechanism. Methods: Twenty SPF db/db mice were randomly divided into model group(n=10) and Shenyuan Granule group(n=10), and the wild type (WT) mice were chosen as blank group(n=10). After treated for 12 weeks, the serum, kidney tissue and thoracic aorta tissue of the mice in various groups were taken. The serum FGF23 levels of the mice in various groups were detected by ELISA method;HE and von kossa staining were used to detect the pathomorphology of the thoracic aorta and calcium deposition of the mice in various groups; Real-time PCR method was used to detect the expression levels of Klotho mRNA in kidney tissue and Pit-1, Runx2 and SM22α mRNA in thoracic aorta tissue of the mice in various groups; Western blotting method was used to detect the expression levels of Klotho protein in kidney tissue and Pit-1, Runx2 and SM22α proteins in thoracic aorta tissue of the mice in various groups; immunohistochemisty method was used to detect the expression levels of Pit-1 protein in thoracic aorta tissue of the mice in various groups,and immunofluorescence method was used to detect the expression levels of SM22α and Runx2 proteins in thoracic aorta tissue of the mice in various groups. Results: Compared with blank group, the serum FGF23 level of the mice in model group was significantly increased (P<0.05), the expression levels of Klotho mRNA and protein in kidney tissue were significantly decreased (P<0.01), the expression levels of Pit-1 and Runx2 mRNA and proteins in thoracic aorta tissue were increased (P<0.01), the expression levels of SM22α mRNA and protein in thoracic aorta tissue were decreased (P<0.01),the expression levels of Pit-1 and Runx2 proteins in thoracic aorta tissue were increased(P<0.01), and the expression level of SM22α protein in thoracic aorta tissue was decreased (P<0.01).Compared with model group, the serum FGF23 level of the mice in Shenyuan Granule group was decreased (P<0.05), the expression levels of Klotho mRNA and protein in kidney tissue were increased(P<0.01), the expression levels of Pit-1 and Runx2 mRNA and protein in thoracic aorta tissue were decreased (P<0.01), and the expression levels of SM22α mRNA and protein in thoracic aorta tissue were increased (P<0.01). Conclusion: Shenyuan Granule can up-regulate the expression level of Klotho protein in kidney tissue of the mice, reduce the expression level of Pit-1, inhibit the FGF23/Pit-1 signaling pathway, and regulate the phenotypic transformation of vasular smooth muscle cell(VSMC) to achieve its protective effect on the blood vessels.

Key words: Klotho, diabetic nephropathy, vascular smooth muscle cells, Shenyuan Granule, vascular calcification