[Protective effects of Hirsutella sinensis on renal interstitial fibrosis: experiment with rat model of chronic aristolochic acid nephropathy].
OBJECTIVE
To study the protective effects of Hirsutella sinensis on renal interstitial fibrosis in chronic aristolochic acid nephropathy (CAAN).


METHODS
Eighteen male SD rats were divided into 3 equal groups: model group, given the extract of Aristolochia manshuriensis Kom (AmK) by gavage in the morning everyday for 12 weeks, intervention group, given the extract of Amk in the morning and suspension of Hirsutella sinensis in the afternoon by gavage once a day for 12 weeks, and control group, receiving tap water only by gavage. Bodyweight, urinary glucose, 24 h urinary protein excretion, and serum creatinine (SCr) were measured at the ends of the 1st, 4th, 8th, and 12th weeks respectively. At the end of the 12th week, all the rats were sacrificed with their kidneys taken out to undergo pathological examination. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and type I collagen (ColI) in the kidney tissues.


RESULTS
Since the 1st week, the 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 area of interstitial fibrosis of the model group was significantly enlarged (P < 0.01). The mRNA expression levels of TGF-beta1, CTGF, PAI-1, TIMP-1, and ColI in the model group were up-regulated by 4.19, 2.66, 6.12, 3.09, and 7.03 times respectively, and their protein expression levels were up-regulated by 2.31, 3.53, 3.17, 3.18, and 6.87 times respectively (all P < 0.01). By the end of the 12th week, the urinary protein excretion, SCr level and the relative area of interstitial fibrosis in the intervention group were all significantly lower than those in the model group (all P < 0.05). The mRNA expression levels of TGF-beta, CTGF, PAI-1, TIMP-1, and ColIof the intervention group were all significantly lower than those of the model group (all P < 0.05) with the inhibition rates of 45%, 41%, 47%, 48%, and the protein expression levels of TGF-beta, CTGF, PAI-1, TIMP-1, and ColI of the intervention group were all significantly lower than those of the model group (all P < 0.05) with the inhibition rates of 38%, 39%, 49%, 46%, and 61% respectively.


CONCLUSIONS
Hirsutella sinensis can inhibit the production of TGF-beta1 and CTGF, factors that promote the extracellular matrix (ECM) synthesis and TIMP-1 and PAI-1, factors that antagonize ECM degradation in kidney tissues, thus alleviating renal interstitial fibrosis and improving renal function in CAAN.
Zhu
Yun-feng
YF
Center of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China.
Chen
Yi-Pu
YP
Rui
Hong-liang
HL
Dong
Hong-rui
HR
Hu
Zhao
Z
D000818:Animals; D034341:Aristolochic Acids; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D004195:Disease Models, Animal; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D006999:Hypocreales / Q000737:chemistry*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D034341:Aristolochic Acids; D001688:Biological Products; C526316:CCN2 protein, rat; D024042:Collagen Type I; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor