ABSTRACT
Objective:To investigate the intervention mechanism of Yishen Huayu prescription on glomerular podocyte injury in diabetic nephropathy （DN） rats based on epithelialmesenchymal transition （EMT） regulated by Wnt/<italic>β</italic>-catenin pathway. Method:The 60 SD rats were divided into control group， model group， Wnt-C59 group （0.03 g·kg<sup>-1</sup> Wnt/<italic>β</italic>-catenin pathway inhibitor）， low-dose group （8 g·kg<sup>-1</sup>）， medium-dose group （16 g·kg<sup>-1</sup>） and high-dose group （32 g·kg<sup>-1</sup>）. After 12 weeks， various indexes ， including general signs， serum creatinine （SCr）， blood urea nitrogen （BUN）， renal index， urinary protein， blood glucose， renal pathological changes， podocyte and expressions of glomerular basement membrane injury and podocyte injury related proteins ［nephrin， synaptopodin］， Wnt/<italic>β</italic>-catenin pathway related proteins （Wnt1， <italic>β</italic>-catenin）， podocyte EMT related protein ［<italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA）， E-cadherin］， were compared between groups. Result:Compared with the control group， the renal tissue in the model group showed significant pathological changes， including diffuse thickening of glomerular mesangial matrix and severe foot process fusion， and a significant increase in SCr， BUN， renal indexes， urinary protein， blood glucose， Wnt1， <italic>β</italic>-catenin， and <italic>α</italic>-SMA expression levels （<italic>P</italic><0.05） as well as a significant decrease in nephrin， synaptopodin and E-cadherin expression levels（<italic>P</italic><0.05）. Compared with model group， SCr， BUN， renal index， urinary protein， blood glucose， Wnt1， <italic>β</italic>-catenin， and <italic>α</italic>-SMA expression levels in each intervention group significantly decreased （<italic>P</italic><0.05）， while the expression levels of nephrin， synaptopodin and E-cadherin significantly increased （<italic>P</italic><0.05）. Among intervention groups， the improvement of above indexes in high-dose Yishen Huayu prescription group was the most obvious （<italic>P</italic><0.05）， which was similar to the effect in Wnt-C59 group. Conclusion:Yishen Huayu prescription prevents podocyte EMT by inhibiting Wnt/<italic>β</italic>-catenin pathway， thereby repairing glomerular podocyte injury in rats with diabetic nephropathy.
ABSTRACT
Objective:To study the effect of Shenshuai Xiezhuo decoction and its deficiency tonifying and pathogen eliminating components on renal interstitial fibrosis in UUO rats. Method:A rat model of unilateral ureteral obstruction (UUO) was established through ligation of a unilateral ureter. The rats were divided into six groups: sham operation group, model group, benazepril group, Shenshuai Xiezhuo decoction group, Buxufang group, and phlegm group, with 24 rats in each group. On the third day after operation, the rats in the Shenshuai Xiezhuo decoction group, Buxufang group, and phlegm group were given Shenshuai Xiezhuo decoction concentrating agent at a dose of 8.0 g·kg-1·d-1, the rats in the benazepril group were given benazepril 1.5 mg·kg-1·d-1, and the rats in the sham operation group and the model group were given the same volume of saline. On the 7th, 14th and 21st days after operation, the expressions of peripheral cells and relevant signal pathway markers in renal tissue were detected by Western blot and Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) respectively. Result:The stromal damage score and the interstitial collagen accumulation on the 14th and 21st days after UUO were significantly lower in the Shenshuai Xiezhuo decoction group, Buxu prescription group and Qixie prescription group than those in the model group (P<0.05). Except for the sham operation group, the protein expressions of α smooth muscle actin (α-SMA), platelet derived growth factor A (PDGFA), nerve/glial type 2 chondroitin sulfate glycoprotein (NG-2), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 1 (VEGFR1), platelet-derived growth factor -β (PDGF-β) and platelet-derived growth factor receptor-β (PDGFR-β) in the kidney tissues of the 14th and 21st days were significantly increased compared with those on the 7th day (P<0.05). On the 21st day after surgery, the expressions of NG-2, VEGFA, VEGFR1 and PDGFR-β in renal tissue of Shenshuai Xiezhuo decoction group were significantly lower than those in the model group (P<0.05). Compared with the model group, relevant expressions of α-SMA, PDGFA, NG-2, VEGFA, VEGFR1, PDGF-β, and PDGFR-β in kidney tissue of Shenshuai Xiezhuo decoction group decreased significantly on the 21st day after operation (P<0.05), and relative expressions of α-SMA, NG-2, VEGFA, VEGFR1 and PDGFR-β in the Shenshuai Xiezhuo decoction group were significantly lower than those in the benazepril group on the 21st day after surgery (P<0.05). Conclusion:Shenshuai Xiezhuo decoction and its deficiency tonifying and pathogen eliminating components have an antagonistic effect on renal interstitial fibrosis in UUO rats. Its mechanism is related to the inhibition of activation of peripheral cells and relevant cell signaling pathways.