Effect of Radix Astragali on TGF-β1/Smads Signaling Pathway in Epithelial-mesenchymal Transition of rat Peritoneal Mesothelial Cells Induced by High-glucose Peritoneal Dialysate

OBJECTIVE To observe the effect of Radix Astragali on TGF-β1/Smads signaling pathway in epithelial-mesenchymal transition(EMT) of rat peritoneal mesothelial cells induced by high-glucose peritoneal dialysis and explore the inhibitory influence and mechanism of Radix Astragali on peritoneal fibrosis.METHODS They were divided into 2 groups， 10 rats in each. The contrast group's rats were intraperitoneal injected 35days normal saline 20 mL/rat. The model group's rats were intraperitoneal injected 35days Icodextrin 20 mL/rats. The low/middle and high doses astragalus mongholicus groups: After 16 days modeling， the rats were intraperitoneal injected 20 days astragalus mongholicus extraneal(put astragalus mongholicus injections into the externeal， and the concentation of crude drug is 10 mg/mL，20 mg/mL and 40 mg/mL) 20 mL/rats. The peritoneal pathological changes were observed through HE staining; the expressions of abdominal membrane TGF-β1， Collagen I， Collagen III， FN， E-cadherin， α-SMA were examined through rapid immunohistochemical method; the expressions of proteins of peritoneal tissues TGF-β1， E-cadherin， α-SMA， Smad2/3， p-smad2/3， of Smad7 were detected through Westernblot; the expressions of TGF-β1， E-cadherin， α-SMA， Smad7mRNA were detected through RT-PCR.RESULTS ①PMCs in model group were round or oval with cells falling off， subcutaneous matrix proliferating， a large number of fibroblast-like cells and monocytes and macrophage infiltrating， fibrinoid material depositing and the expression of peritoneal tissues TGF-β1， Collagen I， Collagen III and FN increasing. The astragalus intervention groups showed improvement in the above conditions with the high-dose group the most obvious. ②The expression of α -SMA in model group labeled by EMT showed an up-regulation while that of E-cadherin low-regulation. The middle and high doses of Radix Astragali groups could reverse the decrease in expression of E-cadherin in peritoneal tissues and high expression of α-SMA to some extent. ③In model group， the expression of signal proteins p-Smad2/3 and Smad7 showed an up-regulation. Radix Astragali could decease the high expression of p-Smad2/3 in different degrees and strengthen the expression of Samd7 taking the high-dose group as the more significant effect.CONCLUSION High-glucose abdominal dialysis fluid can prompt the occurrence of PMCsEMT while Radix Astragali may inhibit TGF-β1 and effect the key signal proteins Smad2/3 and Smad7 in the positive and negative feedback loop of Smads signal transduction pathways to prevent the occurrence of PMCsEMT.