Protective effect of emodin on renal interstitial fibrosis in mice of unilateral ureteral obstruction via PI3K/Akt/mTOR signaling pathway / 中华肾脏病杂志

ABSTRACT

Objective To investigate the effect and mechanism of emodin (EM) in renal interstitial fibrosis of unilateral ureteral obstruction (UUO) mice.Methods Male C57BL/6J mice were randomly divided into 4 groups,including sham operation group (n=8),UUO operation group (n=8),UUO operation+losartan (LST) group (n=8) and UUO operation+EM group (n=8).The mice in each group were ingested the suspensions by gavage for 14 days after surgery.Mice in UUO+LST and UUO+ EM groups were given 10 mg· kg-1· d-1 LST and 20 mg· kg-1 · d-1 EM,respectively.LST and EM were mixed with 0.5％ sodium carboxymethyl cellulose.Mice in sham group and UUO group were given 0.5％ sodium carboxymethyl cellulose.The mice were sacrificed at the 14th day.Interstitial fibrosis was observed by HE,Masson and PAS stain.Real-time PCR was used to detect LC3,Beclin-1 and mTOR mRNA.Protein expressions of TGF-β1,α-SMA,E-cadherin,LC3,Beclin-1,PI3K,p-Akt and mTOR were detected by Western blotting.The autophagy was observed with transmission electron microscopy in the renal tissue.Results Compared with sham mice,UUO mice at the 14th day displayed obvious renal fibrosis.Meanwhile,UUO mice had increased expressions of TGF-β1 and α-SMA (all P ＜ 0.01),and decreased expressions of E-cadherin (P ＜ 0.01).Their renal expressions of PI3K,p-Akt and mTOR were also raised (all P ＜ 0.01).Compared with those in UUO group,in UUO+LST group and UUO+EM group,expressions of autophagy protein LC3 and Beclin-1 were increased (all P ＜ 0.01),and the number of autophagic was increased.Additionally,expressions of TGF-β1 and α-SMA were reduced in UUO+LST group and UUO+EM group (all P ＜ 0.01),while the expression of E-cadherin was increased by emodin treatment (P＜ 0.05).And expressions of PI3K,p-Akt and mTOR were decreased in UUO + LST group and UUO + EM group (all P ＜ 0.05),meanwhile renal tissue fibrosis significantly reduced.Conclusions Emodin can promote autophagy,ameliorate renal interstitial fibrosis and protect renal function through PI3K/Akt/mTOR signaling pathway.