Protective effect of shikonin on renal fibrosis via Smad3/long-chain non-coding Erbb4-IR axis / 中国药理学通报

ABSTRACT

Aim To investigate the therapeutic effect of shikonin on unilateral ureteral obstructive nephropathy (UUO)-induced CKD mouse fibrosis model and the potential regulatory mechanism. Methods Thirty C57BL/6 mice (8 weeks old, weighing 20-22 g) were randomly divided into sham group, UUO model group, low dose shikonin group (5 mg • kg"1) , high dose shikonin group (20 mg • kg"1) and irbesartan group (20 mg • kg"1). Mice in shikonin groups were given the first drug intragastrically for one day before operation, and then were sacrificed for 10 days after continuous gavage. Creatine and urea nitrogen were detected, renal pathology was observed by HE and PAS, renal interstitial fibrosis was detected by MAS-SON, a-SMA was detected by IHC, and ot-SMA, FN, p-Smad3, Smad3 and Smad7 expression in renal tis-sues were detected by Western blot. TGF-p and long-chain non-coding Erbb4-IR were detected by RT-PCR. Results Compared with model group, serum creatinine and urea nitrogen significantly decreased after treatment with shikonin. HE showed marked improvement in renal tubular injury. PAS and MASSON staining showed decreased glycogen deposition and fibrosis. Western blot showed shikonin inhibited the activation of the key protein Smad3 in the TGF-p/Smad signaling pathway and up-regulated the expression of Smad7, while the expression of TGF-(3 and long-chain non-encoding Erbb4-IR decreased in a dose-dependent manner. Conclusions Shikonin can effectively alleviate renal fibrosis, and its mechanism may be related to the regulation of Smad3/long-chain non-coding Erbb4-IR axis.