The aqueous extract of You-Gui-Yin improves renal microcirculatory disturbances in chronic renal failure rats by activating the EPO/PI3K/AKT/VEGF pathway

Abstract

Background You-Gui-Yin (YGY) is a traditional Chinese recipe used for treating renal function diseases which is recorded in Jingyue Quanshu written by Zhang Jingyue in Ming dynasty. According to traditional Chinese medicine theory,Insufficient kidney yang leads to blood blockage and tends to create localised blood microcirculation disorders. However, the mechanism by which Right Return Drink improves microcirculatory disorders has not been discovered. Methods The potential therapeutic effects of YGY extract on chronic renal failure were investigated in vivo using adenine-induced chronic renal failure rats. Firstly, we observed the therapeutic effects of YGY extract on renal impairment, histopathological patterns and serum biochemical parameters in adenine-induced chronic renal failure rats. Secondly, in pre-laboratory data, YGY was found to promote EPO production in rats and mice. Modern pharmacological studies have found that EPO has a role in angiogenesis, and that normal microvascular function and morphology are directly related to the performance of the renal microcirculation. Subsequently, to assess the effect of EPO on renal microcirculation, we monitored changes in renal microcirculation using EPO cKO mice, using photoacoustic imaging (PAI). Finally, the expression of renal EPO, EPOR, PI3K, p-PI3K (p110), AKT, p-AKT (Ser473), and VEGF proteins was examined by Western blot and other techniques to investigate the possible mechanisms of EPO-induced renal microcirculatory disorders and the possible intrinsic mechanisms of YGY extracts to improve microcirculation, and whether they are related to the promotion of angiogenesis and improving vascular function. Results EPO−/− mice produce significant pathological damage to the mouse kidney due to low levels of EPO protein, and the damage to their renal microcirculation is manifested by abnormal renal hemodynamics, and significant abnormalities in renal blood supply and oxygen saturation. YGY extract ameliorated the microcirculatory impairment in rats with chronic renal failure. In detail, YGY extract improved renal function by restoring the damaged renal capillary network, increasing renal blood flow, and expanding renal blood distribution to maintain vascular function. In addition, the expression of PI3K/AKT/VEGF pathway was significantly reduced in the kidney of EPO−/− mice, indicating that this pathway may be a relevant pathway for renal microcirculatory disorders caused by the lack of EPO. And the potential mechanism of YGY to improve microcirculatory disorders may be related to the activation of EPO/PI3K/AKT/VEGF pathway. Conclusions YGY extract was shown to prevent the deterioration of renal function and renal microcirculation in rats with adenine-induced chronic renal failure, possibly by a mechanism related to the activation of the EPO/VEGF signalling pathway.