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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。
To investigate the protective effect of isorhamnetin on acute renal injury induced by ischemiareperfusion in rats and its possible mechanism. Forty male SD rats were randomly divided into control group, IR group, low dose isorhamnetin group (ISO-50) and high dose isorhamnetin group (ISO-150), ISO-50 and ISO- The rats were given different doses of isorhamnetin (50mg / (kg · d) and 150mg / (kg · d)] for 14 days before modeling respectively. After 24h of IR injury, serum creatinine, C and urinary KIM-1 levels were measured. The protein and gene expression of NF-κB p65 and phosphorylated NF-κB p65 in renal tissue were assayed for the activity of NF-κB p65 DNA while the activity of NF- The protein and gene expressions of TGF-β1, TNF-α, IL-6 and ICAM-1, the downstream inflammatory factors of NF-κB pathway, were assayed for the activity of superoxide dismutase (SOD) (malondialdehyde, MDA). The paraffin section was made in the kidney by the routine method. The damage of the renal tubules was observed under light microscope after HE staining. It was found that isorhamnetin can reduce serum creatinine, cystatin C and urinary KIM-1 levels, reduce the tubular Paller score, inhibit the activation of NF-κB signaling pathway and inflammatory cytokines expression, and reduce renal oxidative stress; ISO-150 group renal protection than ISO-50 group more obvious. The results suggest that isorhamnetin preconditioning has a protective effect on acute kidney injury (IRI) caused by IR injury in a dose-dependent manner in rats, which may be related to the inhibition of NF-κB signal transduction system Over-activation and oxidative stress.