The Expression Of PI3K/Akt Pathway In The Renal Tissueof Lupus Nephritis

Object:In this study MRL/faslpr mice were used to investigate the potential role of PI3K/Akt/NF-κB/FoxO1 pathway in the pathological changes of lupus nephritis, which will provide an important basis for the target therapy of lupus nephritis.Methods:1 The pathological changes of MRL/faslpr mice by HE and PAS stainingTen female MRL/MPJ mice and MRL/faslpr mice (weight 45-55g) were respectively designed as Control group and LN group (lupus nephritis group). Mice were sacrificed at 40 week and renal cortex was collected. HE staining and PAS staining were used to observe the morphological structure of renal cortex.2 The expression of p85, p110 and p-Akt protein in the glomeruli of MRL/faslpr mice by immunofluorescence technologyPart of renal tissues was cryopreserved liquid nitrogen; 5μm frozen sections were obtained for the observation of p85, p110 subunits and p-Akt protein by immunofluorescence technology.3 The expression of p65 and FoxO1 protein in the glomeruli of MRL/faslpr mice by immunohistochemical stainingPart of the renal tissues were fixed in 10% neutral formalin and embedded in paraffin,4μm paraffin sections were obtained for the observation of p65 subunits and FoxO1 protein by immunohistochemical staining.Results:1 40-week MRL/faslpr mice developed multiple renal pathological changesHE staining showed that the MRL/faslpr developed multiple renal pathological changes, including the increase of cell number in glomeruli, karyorrhexis, necrocytosis, glomeruli sclerosis, tubular epithelial cells degeneration, inflammatory cell infiltration in interstitial area and fibropla sia compared with Control group. The results of PAS staining showed that glomerular basement membrane thicken and mesangial area broaden in the MRL/faslpr mice compared with Control group.2 The expression of p85, p110 and p-Akt protein in the glomeruli of MRL/faslpr mice were up-regulatedImmunofluorescence results showed that the p85, p110 and p-Akt protein were both located in the nucleus and cytoplasm of glomeruli cells of MRL/MPJ and MRL/faslpr mice. And compared with Control group, the expression of p85, p110 and p-Akt protein in the glomeruli of MRL/faslpr mice were up-regulated.3 The nuclear expression of p65 protein in the glomeruli cells of MRL/faslpr mice was up-regulatedImmunohistochemical staining showed that the positive expression of p65 protein was mainly located in the nucleus of glomeruli in LN group, while in Control group located in the cytoplasm of tubular epithelial cells, and there were negative expression of p65 in glomeruli of control group.4 The expression of FoxO1 protein in the cytoplasm of tubular epithelial cells was up-regualtedImmunohistochemical staining showed that the positive expression of FoxO1 protein was mainly located in the cytoplasm of tubular epithelial cells in LN group, while it was located in the nucleus of tubular epithelial cells in Control group.Conclusions:140-week MRL/faslpr mice developed multiple renal pathological changes that strikingly similar to the LN patients, suggesting that MRL/faslpr mice were classic and ideal animal models for lupus nephritis.2 The PI3K/Akt signaling pathway and its downstream factors NF-κB, FoxO1 were all activated in the development of lupus nephritis in MRL/faslpr mice, which suggested that the PI3K/Akt/NF-κB/FoxO1 signaling pathway maybe involved in the pathogenesis of lupus nephritis.