| Objective:To observe the effect of ET-1 on the renal tubular epithelial-mesenchymal transition in Diabetic nephropathy(DN) rats, and to investigate the anti-fibrosis mechanism of cordyceps sinensis(CS) on the expression of ET-1,α-SMA and E-Cadherin in the kidney of DN ratS。Methods:Male Wistar rats were randomly divided into three groups: the normal control group(Group NC, n=5), the diabetic group(Group DN, n=5) and the Cordyceps sinensis intervention group(Group CS, n=5). Diabetes mellitus rat Models were induced by intraperitoneal injection of streptozotocin(STZ,60mg/kg). Cordyceps sinensis intervention rats received daily intragastric administration at a dose of 5g/(kg·d) after the DN models were successfully established. Five rats of each group were sacrificed respectively at the 4th week. The 24-hour urinary protein and serum creatinine were detected, and HE and Masson stain were separately employed to observe renal histological changes. The protein expression of ET-1, E-Cadherin,α-SMA in the kidney tissue was assessed by immunohistochemistry while their mRNA expression was examined by RT-PCR.Results:1. Compared with the NC Group, the expression of ET-1 andα-SMA in the kidney of DN rats was increased significantly, while the expression of E-Cadherin was decreased(p<0.05 or p<0.01). ET-1 had positive correlation withα-SMA and negative correlation with E-Cadherin (p<0.01), suggesting that ET-1 might induce the development of EMT and renal interstitial fibrosis.2. Compared with the NC Group, blood glucose,24-hour urinary protein and Scr in the DN Group all increased significantly(p<0.05 or p<0.01). DN rats displayed glomerular hypertrophy, inflammatory cell infiltration, extracellular matrix increase and renal interstitial fibrosis.3. Compared with the NC Group,24-hour urinary protein,Scr, and renal intestitial fibrosis were reduced in the CS Group (p<0.05 or p<0.01). The expression of ET-1 andα-SMA was significantly decreased and that of E-Cadherin was increased after 4 weeks of Cordyceps sinensis treatment(p<0.05 or p<0.01).Conclusions:1. ET-1 can induce the development of EMT in DN.2. Cordyceps sinensis has renoprotective and anti-fibrotic effects in DN rat models, and the probable mechanism is through reduction of ET-1 production leading to decrease inα-SMA expression and increase in E-Cadherin expression. |
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