摘要
目的:探讨磷脂酰肌醇3-激酶/核因子E2相关因子2(PI3K/Nrf2)信号通路在内毒素休克兔急性肾损伤中的作用。方法:健康清洁级雄性新西兰大白兔50只,随机分为5组(每组10只):对照组(C组)、内毒素休克模型组(L组)、渥曼青霉素+内毒素休克组(WL组)、渥曼青霉素组(W组)和二甲基亚砜组(D组)。W组、WL组经耳缘静脉注射渥曼青霉素0.6 mg/kg,D组注射二甲基亚砜0.08 m L/kg,C组和L组注射等容量生理盐水。30 min后,L组和WL组静脉注射脂多糖5 mg/kg(溶于2 m L生理盐水),C组、W组和D组注射等容量生理盐水。注射脂多糖或生理盐水后6 h处死兔,取肾组织进行肾损伤评分(HSK),测定血尿素氮(BUN)、肌酐(Cr)和尿α1-微球蛋白(α1-MG)浓度,检测肾组织MDA含量及SOD活性,检测肾组织Nrf2和HO-1的mRNA总Akt蛋白、p-Akt蛋白、总Nrf2蛋白、p-Nrf2蛋白、核Nrf2蛋白和HO-1蛋白水平。结果:与C组、W组及D组比较,L组和WL组HSK、BUN、Cr、α1-MG及MDA含量升高,SOD活性降低,肾组织Nrf2和HO-1的mRNA、p-Akt蛋白、Nrf2总蛋白、pNrf2蛋白、Nrf2核蛋白及HO-1蛋白的水平上调(P<0.05)。C组、W组和D组之间上述指标差异无统计学显著性。与L组比较,WL组HSK、BUN、Cr、α1-MG及MDA含量升高,SOD活性降低,肾组织Nrf2和HO-1的mRNA、pAkt蛋白、Nrf2总蛋白、p-Nrf2蛋白、Nrf2核蛋白及HO-1蛋白的水平降低(P<0.05)。结论:PI3K/Nrf2通路激活是内毒素休克诱发兔急性肾损伤时机体的适应性调节反应机制之一。
AIM： To evaluate the role of phosphatidylinositol 3-kinase/nuclear factor E2-related factor 2（ PI3K/Nrf2） signaling pathway in endotoxin-induced acute kidney injury in rabbits. METHODS： Healthy male New Zealand white rabbits were randomly divided into 5 groups： control group（ group C）,LPS group（ group L）,wortmannin ＋LPS group（ group WL）,wortmannin group（ group W） and dimthyl sulfoxide（ DMSO） group（ group D）. Wortmannin at dose of 0. 6 mg / kg was injected via the auricular vein in groups W and WL,DMSO at concentration of 0. 08 m L / kg was injected in group D,while normal saline（ 0. 08 m L / kg） was injected in groups C and L. LPS at dose of 5 mg / kg was injected via the auricular vein in groups L and WL 30 min later,and equal volume of normal saline was injected in group C,D and W for control. The rabbits were sacrificed 6 h after LPS or normal saline administration. The kidneys were removed for microscopic examination and the determination of histological scores of kidney（ HSK）. The concentrations of blood urea nitrogen（ BUN） and creatinine（ Cr）,urinary α1-microglobulin（ α1-MG）,MDA content,SOD activity,the mRNA expression of Nrf2 and HO-1,and the protein levels of total Akt,p-Akt,total Nrf2,p-Nrf2,nuclear Nrf2 and HO-1 in the renal tissues were also detected. RESULTS： Compared with groups C,D and W,the concentrations of BUN and Cr,urinaryα1-MG concentration,MDA content and HSK were significantly increased,while SOD activity was significantly decreased（ P 0. 05）. The mRNA expression of Nrf2 and HO-1,and the protein levels of p-Akt,total Nrf2,p-Nrf2,nuclear Nrf2 and HO-1 in the renal tissues were significantly increased in groups L and WL. No significant change among groups C,D and W was observed. Compared with group L,the concentrations of BUN and Cr,urinary α1-MG concentration,MDA content and HSK were significantly increased,while SOD activity,the mRNA expression of Nrf2 and HO-1,and the protein levels of p-Akt,total Nrf2,p-Nrf2,nuclear Nrf2 and HO-1 in the renal tissues were significantly decreased in group WL.CONCLUSION： Activation of PI3 K / Nrf2 signaling pathway may be one of the regulatory mechanisms of the body adapting to the endotoxin-induced acute kidney injury in rabbits.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2016年第1期129-133,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81372096)
