Mechanism of Notoginseng Radix et Rhizoma in regulating PI3K/Akt/mTORC1-mitochondrial energy metabolism to treat chronic renal failure in rats with blood stasis syndrome
This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein ki-nase B(Akt)/mammalian target of rapamycin complex 1(mTORC1)signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney.Thirty male rats with adriamycin-induced renal fibrosis were randomized into model,low-,medium-,and high-dose Notoginseng Radix et Rhizoma,and positive control groups(n=6).Six clean SD male rats were selected into the normal group.The normal group and model group were administrated with normal saline,and other groups with corresponding drugs.After 8 weeks of treatment,the renal function,renal pathology,adenosine triphosphate(ATP)levels,Na+-K+-ATPase and Ca2+-Mg2+-ATPase activi-ties,and the protein levels of ATP5B,mTORC1,70 kDa ribosomal protein S6 kinase(P70S6K),P85,Akt,p-Akt,and SH2-contai-ning inositol phosphatase(SHIP2)in the renal tissue were determined.Compared with the normal group,the model group showed ele-vated levels of blood urea nitrogen(BUN)and serum creatinine(SCr)(P＜0.01).Compared with the model group,Notoginseng Ra-dix et Rhizoma and the positive control lowered the levels of BUN and SCr,which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P＜0.05).Compared with the model group,Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue,such as vacuolar and fibroid changes,glomeru-lus atrophy,cystic expansion of renal tubules,and massive infiltration of inflammatory cells.Compared with the normal group,the model group showed decreased mitochondrial ATP content and Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in the renal tissue(P＜0.05),and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P＜0.05).Compared with the model group,medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the pro-tein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1,P70S6K,P85,Akt,and p-Akt(P＜0.05 or P＜0.01 or P＜0.001).Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism,thus protecting the kidney.
Notoginseng Radix et Rhizomablood stasismitochondrial energy metabolismPI3K/Akt/mTORC1renal fibrosis
万方数据
维普
