异鼠李素对大鼠缺血再灌注急性肾损伤的免疫保护作用

发布时间：2018-02-28 18:11

本文关键词： 异鼠李素缺血再灌注肾保护 NF-κB信号通路氧化应激　出处：《现代免疫学》2017年06期 　论文类型：期刊论文

【摘要】：探讨异鼠李素对大鼠缺血再灌注(ischemia reperfusion,IR)急性肾损伤的保护作用及可能的作用机制。将40只雄性SD大鼠随机分为对照组、IR组、低剂量异鼠李素组(ISO-50)和高剂量异鼠李素组(ISO-150),ISO-50和ISO-150组分别在造模前给予口服不同剂量的异鼠李素[50mg/(kg·d)和150mg/(kg·d)]14d,IR损伤造模24h后测定各组大鼠血肌酐、胱抑素C及尿KIM-1水平;测定肾组织NF-κB p65、磷酸化NF-κB p65的蛋白及基因表达的同时检测NF-κB p65DNA的活性以评估NF-κB信号通路的活性;测定肾组织中NF-κB通路的下游炎性因子TGF-β1、TNF-α、IL-6及ICAM-1的蛋白和基因表达,同时测定肾组织超氧化物歧化酶(superoxide dismutase,SOD)活力及丙二醛(malondialdehyde,MDA)含量;肾组织按常规方法制作石蜡切片,HE染色后光镜下观察肾小管损伤程度。研究发现异鼠李素能降低血肌酐、胱抑素C及尿KIM-1水平,降低肾小管Paller评分,抑制NF-κB信号通路的活化及炎性因子的表达,并减轻肾组织的氧化应激;ISO-150组的肾保护作用较ISO-50组更加明显。结果提示异鼠李素预处理对大鼠IR损伤导致的急性肾损伤(acute kidney injury,AKI)有保护作用,且呈剂量依赖性,其作用机制可能是抑制了NF-κB信号转导系统的过度活化及氧化应激。
[Abstract]:To investigate the protective effect and possible mechanism of isorhamnetin on acute renal injury induced by ischemia reperfusion in rats, 40 male Sprague-Dawley rats were randomly divided into control group and IR group. Low dose isorhamnetin group (ISO-50) and high dose isorhamnetin group (ISO-150) and ISO-150 group were given orally different doses of isorhamnin [50 mg / kg 路d) and 150 mg / kg / kg 路d] after 14 d IR injury, the levels of serum creatinine, cystatin C and urinary KIM-1 were measured. The protein and gene expression of NF- 魏 B p65 and phosphorylated NF- 魏 B p65 were determined to evaluate the activity of NF- 魏 B signaling pathway, and the protein and gene expression of TGF- 尾 1, TNF- 伪 and ICAM-1, the downstream inflammatory factor of NF- 魏 B pathway, were determined. At the same time, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (malondialdehyde) MDAs in renal tissue were measured, and the degree of renal tubular injury was observed under light microscope after paraffin sections were made by routine method. It was found that isorhamnetin could reduce serum creatinine. The levels of cystatin C and urinary KIM-1 decreased the Paller score of renal tubules, inhibited the activation of NF- 魏 B signaling pathway and the expression of inflammatory factors. The renal protective effect of ISO-150 group was more obvious than that of ISO-50 group. The results indicated that isorhamnetin preconditioning had a dose-dependent protective effect on acute kidney injuryaki induced by IR injury in rats. Its mechanism may be to inhibit the excessive activation of NF- 魏 B signal transduction system and oxidative stress.
【作者单位】：潍坊医学院附属医院肾内科;潍坊医学院附属医院血液净化中心;
【分类号】：R692

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