Protective Effects of Piperazine Ferulate on Cyclosporineinduced Chronic Nephrotoxicity in Rats_West China Medical Journal

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Department of Nephrology Sichuan University, West China Hospital, Sichuan University, Chengdu 610041, China;

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Keywords：

环孢霉素A; 慢性肾毒性; 阿魏酸哌嗪

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目的:探讨阿魏酸哌嗪对环孢霉素A（CsA）慢性肾毒性的保护作用。方法:按四组分别给予实验大鼠橄榄油,CsA,CsA加低剂量阿魏酸哌嗪［50 mg/（kg·d）］及CsA加高剂量阿魏酸哌嗪［100 mg/（kg·d）］,四周后取血测血肌酐,计算肌酐清除率,取肾组织测定肾组织和血中的血管紧张素Ⅱ浓度,同时作肾组织病理学检查。通过免疫组化观察肾组织内皮素及Ⅲ型胶原表达情况。结果:CsA大鼠肾脏可见明显损伤,同时肌酐清除率明显下降,血浆及肾组织血管紧张素Ⅱ含量增高,而且肾组织局部内皮素及Ⅲ型胶原表达明显增高。给予阿魏酸哌嗪能使肾损伤有所减轻,使血液及肾组织血管紧张素Ⅱ含量减少,内皮素及Ⅲ型胶原表达下降。结论:CsA引起慢性肾毒性可能与血管紧张素Ⅱ、内皮素和Ⅲ型胶原增加有关,同时应用阿魏酸哌嗪可以使血浆及肾脏组织血管紧张素Ⅱ减少,内皮素和Ⅲ型胶原表达下降,因此对肾脏有保护作用,而且这种作用与剂量有相关性。

Citation： BO Hong,TAO Ye,LIU Qifeng,et al. Protective Effects of Piperazine Ferulate on Cyclosporineinduced Chronic Nephrotoxicity in Rats. West China Medical Journal, 2009, 24(3): 677-680. doi: Copy

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1. BENNETT W M.Clinical aspects of cyclosporine nephrotoxicity[J].Nephrology,1991,1:564..
2. BURDMANN EA, ANDOH TF, NAST CC,et al.Prevention of experimental cyclosporininduced interstitial fibrosis by losartan and enalapril[J].Am J Physiol,1995,269:F491-499..
3. LEE DBN.Cyclosporine and the renin angiotensin axis[J].Kidney Int,1997,52:248-260..
4. BENNETT WM, DEMATTOS A, MEYER MM,et al.Chronic cyclosporine nephropathy: the Achilles heel of immunosuppressive therapy[J]. Kidney Int,1996,50,1089-1100..
5. KURTZ A, BRUNA RD, KüHN K.Cyclosporine A enhances renin secretion and production in isolated juxtaglomerular cells[J].Kidney Int, 1988,33:947-953..
6. BURDMANN EA, ANDOH TF,et al.Prevention of experimental cyclosporininduced interstitial fibrosis by losartan and enalapril[J].Am J Physiol,1995,269:F491-F499..
7. SHIHAB FS, ANDOH TF, TANNER AM,et al.Role of transforming growth factorβ1 in experimental chronic cyclosporine nephropathy[J]. Kidney Int,1996,49:1141-1151..
8. HEALY E, DEMPSEY M, LALLY C,et al.Apoptosis and necrosis: mechanisms of cell death induced by cyclosporine A in a renal proximal tubular cell line[J].Kidney Int,1998,54:1955-1966..
9. KON V, SUGIURA M, INAGAMI T,et al.Role of endothelin in cyclosporineinduced glomerular dysfunction[J].Kidney Int,1990,37:1487-1491.
10. 王峰,刘敏,杨连春.新的非肽类内皮素拮抗剂:咖啡酸、阿魏酸[J].药学学报,1999,34:898-901..
11. GHIGGERI G M, ALTIERI P, OLEGGINI R,et al.Cyclosporine enhances the synthesis of selected extracellular matrix proteins by renal cells in culture[J].Transplantation, 1994,57:13821388..
12. OLEGGINI R, MUSANTE L,MENONI S,et al.Characterization of a DNA binding site that mediates the stimulatory effect of cyclosporinA on type Ⅲ collagen expression in renal cells[J].Nephrol Dial Transplant,2000,15: 778-785..
13. KLAHR S, MORRISSEY J J.The role of vasoactive compounds, growth factors and cytokines in the progression of renal disease[J].Kidney Int,2000,75（Suppl）:S7-S14..

West China Medical Journal

Protective Effects of Piperazine Ferulate on Cyclosporineinduced Chronic Nephrotoxicity in Rats

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