急性肾损伤模型大鼠血清及尿白蛋白的变化及其相关机制的研究

Changes of Serum and Urine Albumin in Acute Kidney Injury Models and the Underlying Mechanisms

目的探讨常见急性肾损伤大鼠模型病理过程中其血清、尿蛋白的变化及其形成的相关机制。方法分别尾静脉注射顺铂,腹腔注射庆大霉素,以及结扎肾动静脉所致肾缺血再灌(简称肾缺血再灌,renal ischemia reperfusion,RIR)等方法,造成大鼠急性肾损伤。观察肾组织形态学变化,检测血清和24 h尿总蛋白(total protein,TP),白蛋白(albumin,ALB)以及血清肝功肾功相关指标;观察肝脏组织TP,ALB的含量及ALB m RNA、蛋白的表达水平;观察肾组织ALB,肾病蛋白(Nephrin),足突蛋白(Podocin)及炎性坏死因子相关蛋白表达。结果顺铂、肾缺血再灌及庆大霉素大鼠血清中ALB显著下降(P<0.05),同时尿ALB,TP显著升高(P<0.05)。顺铂模型肝TP及ALB m RNA及蛋白表达下调,庆大霉素及肾缺血再灌模型肝TP含量显著升高(P<0.05),ALB m RNA表达上调。三种模型大鼠肾组织Nephrin,白介素-6(interleukin-6,IL-6),肿瘤坏死因子(tumor necrosis factor-α,TNFα),ALB蛋白表达均明显升高(P<0.05);顺铂及肾缺血再灌大鼠肾Podocin表达明显下调;同时3种模型大鼠肾组织均可见基底膜损伤,肾小管上皮细胞出现不同程度的坏死。结论3种急性肾损伤大鼠尿蛋白排泄升高和血清ALB下降,与肾小球基底膜及肾小管上皮细胞损伤相关。同时肝脏和肾脏不同程度上启动了ALB表达合成。3种模型所致其病理生理变化不完全相同,因此在相关防治急性肾损伤中药研究中,还须对不同造模方法进行有针对性的观察。

Objective To investigate and verify the changes of serum and urine protein in the pathological process of acute kidney injury(AKI)rat and the underlying mechanisms involving in this change.Methods The injection of cisplatin into the tail vein,intraperitoneal injection of gentamicin,and renal ischemia and reperfusion(RIR)were carried out for the modeling of acute kidney injury rats.The morphological changes of kidney were observed,serum and 24-hour urine TP(total protein),ALB(albumin),and the index reflecting liver function and kidney function were detected;in addition,the liver tissue TP,ALB content and ALB expression were observed;and the protein expression ALB,Nephrin,Podocin and inflammatory necrosis factor in the kidney were performed.Results Serum ALB(sALB)in cisplatin,RIR and gentamicin rats significantly decreased after modeling(P<0.05),and urine ALB(uALB)and TP(uTP)increased distinctly(P<0.05).The expression of TP and ALB mRNA and protein in liver of cisplatin model was down-regulated,and the liver TP and the expression of ALB mRNA in gentamicin and RIR models was significantly increased(P<0.05).The protein expression of Nephrin,IL-6(interleukin-6),TNFα(tumor necrosis factorα)and ALB in the kidney tissue of model rats was significantly increased(P<0.05);the expression of Podocin in the kidney of cisplatin and RIR rats was significantly down-regulated;meanwhile,glomerulurs basal membrane was injured and renal tubular epithelial cells had different degrees of necrosis.Conclusion The elevated urinary protein excretion and decreased serum ALB in the 3 acute kidney injury rats were associated with glomerular basement membrane and tubular epithelial cell injury.Meanwhile,the liver and kidney initiated ALB expression synthesis to different degrees.the pathophysiological changes due to the three models were not exactly the same,so targeted observation of different modeling methods must also be conducted in the related research of Chinese medicine for preventing and treating acute kidney injury.