Improvement effect of Shenyuan Granule on vascular calcification in db db diabetic nephropathy mice and its mechanism / 吉林大学学报(医学版)

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 (?i=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 SM22a 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 SM22a 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 SM22a 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 ( PmRNA and proteins in thoracic aorta tissue were increased (P<0. 01), the expression levels of SM22a mRNA and protein in thoracic aorta tissue were decreased ( Pproteins in thoracic aorta tissue were increased ( P<0. 01), and the expression level of SM22a protein in thoracic aorta tissue was decreased ( Pserum 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 (PmRNA 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.