摘要
目的:通过观察肿瘤坏死因子α(TNF-α)与核因子κB(NF-κB)在造影剂肾病(CIN)模型大鼠肾组织中的表达,初步探讨CIN发病中是否存在炎症反应机制。方法:将96只雄性SD大鼠随机分成2组:模型组(n=48)和对照组(n=48),分别从尾静脉注射碘造影剂和生理盐水10 mL/kg。在注射后6 h、12 h、24 h、48 h、72 h、5d、10 d和15 d各处死6只大鼠,留取血液和肾组织,采用HE染色法观察肾脏病理变化,免疫组化和RT-PCR法分别检测肾损伤分子1(KIM-1)、NF-κB、TNF-α蛋白和mRNA表达情况,并进行相关性分析。结果:(1)对照组血清肌酐(SCr)和血尿素氮(BUN)各时点变化不大(P>0.05),模型组各时点(除15 d外)SCr和BUN水平明显高于对照组(P<0.05);(2)对照组各时点肾小管无明显损伤,病理评分无显著差异(P>0.05)。模型组的肾小管损伤评分显著高于同一时点的对照组(P<0.05);(3)各因子在造膜后6 h后开始大量表达,KIM-1蛋白及mRNA在24 h达高峰,NF-κB、TNF-α蛋白及mRNA在48 h达高峰,且与对照组对应时点(除15 d外)比较均有显著差异(P<0.05);(4)模型组肾小管损伤评分与NF-κB、TNF-α蛋白及mRNA表达呈正相关(r=0.843、0.758、0.743和0.707,P<0.05);模型组肾组织的NF-κB、TNF-α蛋白及mRNA表达与KIM-1蛋白及mRNA表达呈正相关(r=0.863、0.807、0.839和0.855,均P<0.05)。结论:NF-κB和TNF-α在CIN大鼠肾脏中的表达上调,其表达水平与肾小管损伤程度相关。CIN的发生发展中存在炎症反应机制。
AIM： To observe the expression of tumor necrosis factor α （TNF-α） and nuclear factor KB （ NF—κB） in the renal tissue of the rats with contrast-induced nephropathy （ CIN ）. METHODS： Male Sprague-Dawley rats （ n = 96） were randomly divided into control group （ n = 48） and CIN group （ n = 48）. The model rats in CIN group were intravenously injected with iodinated contrast media （76% compound diatrizoate injection, 10 mL/kg）, while the rats in control group were injected with the same volume of saline. Six rats in each group were sacrificed at 6 h, 12 h, 24 h, 4-8 h, 72 h, 5 d, I0 d and 15 d after intravenous injection, respectively, and the blood and kidney samples of the rats were obtained. The renal tubular injury was assessed by histological examination （HE staining）. The expression of kidney injury molecule-1 （ KIM-1） , TNF-α and NF—κB at mRNA and protein levels in the renal tissues were semiquantitatively measured by the methods of RT-PCR and immunohistochemistry, respectively. The correlations between the expression of TNF-α, NF—κB and tubular injury score, KIM-1 expression in renal tissue of CIN group were analyzed. RESULTS： The levels of serum creatinine （SCr） and blood urea nitrogen （BUN） in control group were not changed between different time points （ P 〉 0. 05 ）. The levels of SCr and BUN in CIN group displayed significant increases at different time points （ except 15 d） compared with control group （ P 〈 0.05）. The renal tubular injury score in CIN group was significantly higher at all time points than that in control group （P 〈 0. 05 ）. The expression of KIM-1, TNF-α and NF—κB at mRNA and protein levels up-regulated significantly at 6 h and the peaking of KIM-1 expression was at 24 h, while the peaking of TNF-α and NF—κB expression was at 48 h in CIN group. The expression of KIM-1,TNF-α and NF—κB was significantly increased in CIN group compared with control group except at 15 d （P 〈 0.05 ）. The expression of TNF-α and NF—κB at mRNA and protein levels showed close correlations with renal tubular injury score （r = 0. 843, 0. 758, 0. 743 and 0. 707, P 〈 0. 05 ）. The expression of TNF-α and NF—κB at mRNA and protein levels was also positively correlated with KIM-1 expression （r = 0. 863, 0. 807, 0. 839 and 0. 855, P 〈 0. 05 ）. CONCLUSION ： The expression of TNF-α and NF—κB at mRNA and protein levels in the renal tissues of CIN group is up-regulated and is closely related with renal tubular injury, indieating that the inflammatory response is involved in the pathogenesis of CIN.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2014年第5期950-956,共7页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.30860110)
关键词
造影剂肾病
肾小管损伤
肾损伤分子1
NF—κB
肿瘤坏死因子Α
Contrast-induced nephropathy
Renal tubular injury
Kidney injury molecule-l
NF-kappa B
Tumor necrosis factor α
