摘要
目的探讨低剂量环孢素A(CsA)对大鼠肾脏缺血再灌注损伤的保护作用及其机制。方法取雄性SD大鼠,切除右肾,左肾动脉阻断1h后开放血供,分为CsA1.5、3.0、5.0mg·kg-1·d-1组和假手术组,以生理盐水组作为对照组。观察肾脏功能和病理学变化,采用免疫组织化学法测定增殖细胞核抗原(PCNA)和细胞凋亡数的表达,采用Western印迹法测定应激活化蛋白激酶(SAPK)的变化。结果与对照组比较,低剂量CsA(1.5mg·kg-1·d-1)组肾脏功能恢复最快(P<0.05),肾小管坏死明显减轻(P<0.05),肾小管凋亡细胞数明显减少(P<0.001),PCNA阳性数明显增加(P<0.01)。各组间肾脏SAPK活性变化的差异无显著性。结论低剂量CsA(<1.5mg·kg-1·d-1)可以明显减轻肾小管细胞凋亡,增强PCNA阳性表达。CsA对肾脏SAPK活性无影响,对肾脏缺血再灌注损伤具有一定的保护作用。
Objective Ischemia-reperfusion injury is unavoidable in cadaveric renal transplantation and contributes to acute tubular necrosis (ATN) as well as the delayed graft function. The nephrotoxicity of cyclosporine A (CsA) limits its application in renal transplantation, especially the ATN. The aim of this study was to investigate the effect of CsA on ischemia-reperfusion injury in rat kidney. Methods Right nephrectomy was performed in the male Sprague-Dawley rats (200-230 g) and left renal ischemia was induced by clamping the left renal artery for 1 h. After the clamp was released, reperfusion was confirmed visually. The animals were divided into 5 groups (n=5) each receiving the following respective treatment: ①CsA 1.5 mg·kg -1·d -1; ②CsA 3.0 mg·kg -1·d -1; ③CsA 5.0 mg·kg -1·d -1; ④Sham-operation; ⑤vehicle: normal saline. CsA and the vehicle were injected via the tail vein before ischemia with additional injection once per day. The animals were sacrificed 1 hour, 12 hours, days 1, 3 and 7 post-ischemia. Serum creatinine (Cr) levels were measured for evaluation of renal function, pathologic changes were evaluated by histologic sections, and immunohistochemistry was performed for proliferating cell nuclear antigen (PCNA) and terminal dUTP nick end labeling (TUNEL). Stress-activated protein kinase (SAPK) activity was determined by Western immunoblot. Results The kidney weight was elevated with increasing length of reperfusion at all time points, however, there was no significant difference between CsA and vehicle groups. At a dose of 5 mg·kg -1·d -1, CsA increased renal ischemia-reperfusion injury as shown by higher Cr levels and by histological evaluation. Low dose CsA (1.5 mg·kg -1·d -1) did not further impair renal damage. Immunostaining revealed that low dose CsA significantly reduced the number of apoptotic cells and increased the number of PCNA positive cells in rat kidney after ischemia/reperfusion injury. In addition, low dose CsA did not affect SAPK activity. Conclusions Low dose CsA (<1.5 mg·kg -1·d -1) did not further impair renal function or prolong recovery from ischemia-reperfusion injury. It reduces significantly the number of apoptotic cells and increases the number of positive PCNA cells induced by ischemia-reperfusion. This may have therapeutic implications in ATN after renal transplantation.
出处
《上海医学》
CAS
CSCD
北大核心
2005年第5期359-362,F006,共5页
Shanghai Medical Journal
关键词
环孢素A
大鼠
肾脏缺血再灌注损伤
保护机制
细胞凋亡
肾脏功能
Cyclosporine A
Ischemia
Apoptosis
Proliferating cell nuclear antigen
Stress-activated protein kinase
