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纸质出版日期:2012
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罗景慧, 杨迎暴. -乙酰半胱氨酸对顺铂诱导急性肾损伤后肾脏组织氧化应激水平的影响[J]. 中国实验方剂学杂志, 2012,18(19):170-175.
LUO Jing-hui, YANG Ying-bao. Effect of -acetylcysteine on Oxidative Stress in Acute Kidney Injury Induced by Cisplatin[J]. Chinese journal of experimental traditional medical formulae, 2012, 18(19): 170-175.
目的:研究顺铂(cisplatin
CDDP)诱导大鼠急性肾损伤(acutekidneyinjury
AKI)后肾脏组织氧化应激水平及N-乙酰半胱氨酸(N-acetylcysteine
NAC)的干预作用。方法:静脉注射CDDP制备大鼠AKI模型。大鼠随机分为空白对照组、AKI模型对照组、NAC低、中、高剂量组(50
100
200mg·kg-1)、维生素C(VitC)对照组(100mg·kg-1)。大鼠预先连续给药3d后
给予CDDP
再继续给药5d。测定大鼠体质量、肾质量、肾脏指数、尿蛋白排泄率。试剂盒测定肾脏组织乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)、15-F2t-异前列烷(15-F2t-Isop)水平。免疫组化法观察8-OHdG阳性细胞。Westernblot测定Cu-Zn-SOD蛋白表达。结果:与空白对照组相比
CDDP诱导AKI模型组体质量、肾质量、肾脏指数下降
尿蛋白排泄率由(0.43±0.09)g显著增加为(2.24±0.41)g
LDH
MDA
15-F2t-Isop
8-OHdG阳性细胞显著增加
CAT
SOD
GSH
GSH-Px和Cu-Zn-SOD表达显著下降(P<0.01)。与AKI模型组相比
NAC组尿蛋白排泄率降低为(0.56±0.19)g
具有显著差异。同时
AKI模型组肾脏指数
LDH
MDA
SOD
CAT
15-F2t-Isop
GSH
GSH-Px水平和8-OHdG阳性细胞数分别为(2.71±0.55)×10-2
(6.92±0.51)KU·mg-1
(68.6±9.2)nmol·mg-1
(61±15)U·mg-1
(5.12±1.04)U·mg-1
(63.2±9.62)ng·mg-1
(159±18)nmol·mg-1
(72±15)U·mg-1
(12.25±2.23)个
NAC组200mg·kg-1组分别为(2.96±0.32)×10-2
(4.62±0.26)KU·mg-1
(39.5±7.9)nmol·mg-1
(109±20)U·mg-1
(9.85±1.21)U·mg-1
(41.8±4.65)ng·mg-1
(225±16)nmol·mg-1
(128±22)U·mg-1
(3.26±0.96)个
两组相比较
具有非常显著差异(P<0.01)
Cu-Zn-SOD表达显著增加(P<0.01)。结论:NAC有效拮抗CDDP的肾损伤作用
可能与其增强肾脏组织抗氧化活性、降低CDDP诱导AKI时肾脏组织氧化应激水平有关。
Objective:To investigate the effect of N-acetylcysteine (NAC) on acute injured kidney (AKI) induced by cisplatin (CDDP). Method:The rats were injected CDDP intravenously to make AKI model. The rats were randomly divided into 6 groups
including the normal control group
CDDP-induced AKI model group
NAC groups (50
100
200 mg·kg-1) and Vit C control group (100 mg·kg-1). NAC and Vit C were administered once a day three days before CDDP was given. And then NAC and Vit C were continuously given ip for five days. The body weight
kidney weight
kidney index
urinary protein excretion rate of rats were determined. The commercial kits were employed to test the concentrations of lactate dehydrogenase (LDH)
malondialdehyde (MDA)
superoxide dismutase (SOD)
catalase (CAT)
reduced glutathione (GSH)
glutathione peroxidase (GSH-Px)
15-F2t-isoprostane (15-F2t-Isop). Eight-OHdG positive cells were counted by immunohistochemical staining. The expression of Cu-Zn-SOD was measured by Western blot. Result:Compared with the normal control group
the weight of body and kidney
kidney index
the concentration of CAT
SOD
GSH
GSH-Px and Cu-Zn-SOD expression were significantly decreased
while urinary protein excretion rate and the concentration of LDH
MDA
15-F2t-Isop
8-OHdG positive cells were significantly increased (P<0.01) in the CDDP-induced kidney injury group. NAC and Vit C significantly reduced urinary protein excretion rate and the concentration of LDH
MDA
15-F2t-Isop
8-OHdG positive cells and increased kidney index
the concentration of CAT
SOD
GSH
GSH-Px and Cu-Zn-SOD expression compared with the AKI model group (P<0.01). Conclusion:NAC protect kidney from CDDP injury by suppressing the oxidative stress.
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