Effect of astragaloside IV based on Toll/MyD88 dependent signaling pathway in treatment of renal fibrosis mice / 中草药

ABSTRACT

Objective To study the effect of astragaloside IV on renal fibrosis mice with unilateral ureteral obstruction (UUO) and discuss the mechanism. Methods Male C57BL/6 50 mice were divided into five groups randomly, such as Sham-operated group, model group and high-, medium-, and low-dose astragaloside IV groups. From the day of surgery, the mice in astragaloside IV groups (high-, medium- and low-dose) were treated by gavage of astragaloside IV for 2 weeks in doses of 50, 30, and 10 mg/(kg∙d) separately. The mice in Sham-operated group and model group were treated with saline instead of astragaloside IV. Serum creatinine and blood urea nitrogen were detected by chemical methods. Histopathological changes and collagen deposition of affected kidney were observed under optical microscope with HE and MASSON staining. The expression levels of Toll/MyD88 dependent signaling pathway related molecules (TLR4, TLR2, MyD88, TRAF6, NF-Kappa B, TNF-α, and IL-6) in affected kidney were measured by immunohistochemistry and Western blotting methods and observed from protein levels in each group. Results The degree of fibrosis and histopathological damage of affected kidney of mice in model group is the most obvious. And the expression levels of Toll/MyD88 dependent signaling pathway related molecules in affected kidney of mice in model group were the highest. With drug concentration increased in groups of astragaloside IV, in these groups, the injury of affected kidney had been obviously reduced, and the protein expression levels of Toll/MyD88 dependent signaling pathway related molecules (TLR4, TLR2, MyD88, TRAF6, and NF-Kappa B) were also in corresponding reduced, at the same time the expression of terminal inflammatory cytokines (TNF-alpha and IL-6) has been suppressed. Conclusion Astragaloside IV may improve renal interstitial fibrosis in mice after UUO by inhibiting the expression of Toll/MyD88 dependent signaling pathway and release of inflammatory cytokines (TNF-alpha and IL-6).