| ObjectiveTo study the protective effects of Hirsutella sinensis on renal interstitial fibrosis in rats with chronic aristolochic acid nephropathy (CAAN).MethodsEighteen male SD rats were equally divided into the following 3 groups: model group in which the rats received the extract of Aristolochiae manshuriensis Kom (AmK) by gavage; intervention group received the suspension of Hirsutella sinensis (1.5g·kg-1·d-1) and AmK by gavage; control group received tap water only by gavage. Each group consisted of 6 rats. Bodyweight, urinary glucose, 24h urinary protein excretion and serum creatinine (SCr) were measured at the end of the 1st, 4th, 8th and 12th week, respectively. At the end of the 12th week, all the rats were sacrificed and the renal pathological examination of each rat was performed. The mRNA and protein expression of transforming growth factor-pi (TGF-β1), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and type I collagen (Col Ⅰ) in kidney tissue was determined by real time RT-PCR and immunohistochemical method, respectively.ResultsFrom the 1st week, urinary protein excretion and SCr levels in the model group were significantly higher than those in the control group (P<0.01 or 0.05). At the end of the 12th week, the relative areas of interstitial fibrosis were significantly enlarged (P<0.01), and the mRNA and protein expression of TGF-β1, CTGF, PAI-1, TIMP-1, Col Ⅰ in kidney tissue was significantly up-regulated (P<0.01) in the model group compared with the control group. Their mRNA expression was up-regulated to 4.19. 2.66,6.12,3.09 and 7.03 times, respectively, and the protein expression was up-regulated to 2.31,3.53,3.17,3.18 and 6.87 times, respectively. At the end of the 12th week, the urinary protein excretion, SCr levels and the relative areas of interstitial fibrosis in intervention group were all significantly lower than those in the model group (P<0.05). The increased mRNA and protein expression of TGF-β1, CTGF, PAI-1, TIMP-1, Col Ⅰ by AmK was all significantly down-regulated in intervention group (P<0.05). Their inhibition rates of mRNA expression were 45%, 41% ,47%,48% and 67%, respectively, and those of protein expression were 38 %,39%, 49%, 46% and 61%, respectively.ConclusionHirsutella sinensis can inhibit the production of promoting extracellular matrix (ECM) synthesis factors (TGF-β1 and CTGF) and antagonizing ECM degradation factors(TIMP-1 and PAI-1) in kidney tissue and, therefore, alleviate the renal interstitial fibrosis and improve renal function in CAAN rats. |
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