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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。
Objective: To investigate the protective effect of piperazine ferulate on chronic nephrotoxicity induced by cyclosporine A (CsA). Methods: The rats were given olive oil, CsA, CsA plus low dose ferulic acid piperazine [50 mg / (kg · d)] and CsA plus high dose ferulic acid piperazine [100 mg / (kg .d)], four weeks after the blood was taken for serum creatinine, creatinine clearance was calculated, and renal tissue was taken to measure the concentration of angiotensin II in the kidney tissue and blood. At the same time, renal tissue pathology was performed. Immunohistochemical observation of renal tissue endothelin and collagen type Ⅲ expression. Results: The renal damage in CsA rats was obvious. At the same time, the creatinine clearance rate was obviously decreased. The content of angiotensin Ⅱ in plasma and kidney increased, and the expression of endothelin and type Ⅲ collagen in renal tissue increased obviously. Administration of ferulic acid piperazine can reduce renal damage, reduce blood and renal tissue angiotensin Ⅱ, endothelin and type Ⅲ collagen decreased. CONCLUSION: Chronic nephrotoxicity induced by CsA may be related to the increase of angiotensin Ⅱ, endothelin and type Ⅲ collagen. At the same time, the administration of ferulic acid piperazine can reduce the content of angiotensin Ⅱ in plasma and kidney, and decrease the expression of endothelin and type Ⅲ collagen , Therefore has a protective effect on the kidneys, and this effect is dose dependent.