[Explorative study on mechanism and drug intervention for chronic allograft nephropathy induced by renal ischemia-reperfusion injury].
OBJECTIVE
This study is aiming to investigate the mechanism and drug intervention of chronic allograft nephropathy (CAN) induced by renal ischemia-reperfusion injury.


METHODS
The closed colony strain Sprague-Dawley (SD) and Wistar Rats were used as donor and recipient, respectively. Orthotopic kidney transplantation was performed following the procedure of our previous study. The rats were divided into five groups: Group A only received CsA with 10 mg/(kg x d); except CsA, Group B,C,D received Yi Sheng injection with 4 mg/(kg x d), 8 mg/(kg x d), and MMF (20 mg/(kg x d)], respectively. Group E was control group. According to Banff standard, the serum creatinine (SCr) level and pathological change of rat grafted kidney were observed at the 4th, 8th and 12th weeks post-transplantation. The immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction were used to comprehend the localization and expression of TGFbeta1 and Smad2, 7 in the transplant kidney.


RESULTS
Compared with the lower dosage group, the differences of SCr level and pathological changes of CAN at all the time points after 8th week were statistically significant in the high dosage Yi Sheng group. It was showed that the Yi Sheng injection had the protective effect on CAN with a dose-dependent fashion. After transplantation, the rat kidney-sclerosis model showed that the up-regulated expressions of TGF-P, and Smad2 and the down-regulated expression of Smad7 in Group A and Group B were statistically significant, which meant that the difference was obvious when Group A compared with the other 4 groups. The expressions of TGF-beta1, and Smad2 were strongly positive in tubular epithelial cell, interstitial cell and glomerulus, while the expression of Smad7 was weak. Thickening of endovascular could significantly be inhibited in high dosage of Yi Sheng and MMF group.


CONCLUSIONS
The up-regulated expressions of TGF-beta1 and Smad2 and the down-regulated expression of Smad7 may accelerate the progression of CAN alone or with immune factors. The traditional Chinese medicine Yi Sheng injection and MMF can down-regulate the expression of TGF-beta1 and Smad2 and block the down-regulated expression of Smad7, which may postpone and lessen the progression of CAN.
Xin
Yu-peng
YP
Department of Urology, West China Hospital, Sichuan University, Chengdu, China.
Yuan
Guang-ya
GY
Lu
Yi-ping
YP
Yang
Yu-ru
YR
Zhang
Xiu-hui
XH
Li
You-ping
YP
Gao
Rui
R
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy*; D016030:Kidney Transplantation / Q000009:adverse effects*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology*; D051899:Smad2 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014184:Transplantation, Homologous
D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D053773:Transforming Growth Factor beta1; D009173:Mycophenolic Acid