茶多酚对脂多糖诱导小鼠急性肾损伤的保护作用及机制

Effects and mechanism of tea-polyphenol on LPS inducing acute kidney injury of mice

目的从氧化应激、炎症反应两方面探讨茶多酚对脂多糖(LPS)诱导小鼠急性肾损伤(AKI)保护作用的可能机制。方法24只雄性无特定病原体(SPF)级体重为(35±3)g的KM小鼠随机分为假手术组、模型组和茶多酚治疗组(治疗组),每组8只。模型组腹腔注射LPS(10mg/kg)诱导复制小鼠AKI模型,假手术组注射等剂量生理盐水。治疗组于术前7天开始,用茶多酚溶液灌胃(200mg/kg,1次/d),其他两组均用等量蒸馏水灌胃,1次/d,持续8d。复制模型24h后眼球取血,分离血清检测血肌酐(Scr)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和尿素氮(BUN)水平,收集24h尿液检测BUN、尿蛋白(Upro)和尿肌酐(Ucr)的水平;取肾脏处理后计算肾脏系数,ELISA法检测肾组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平,并取部分肾脏组织做HE染色切片,观察肾组织损伤情况。结果与假手术组比较,模型组小鼠血清BUN、MDA、Scr水平提高,SOD和GSH-Px水平降低(均P<0.05);尿液BUN、Upro、Ucr水平提高(均P<0.05);肾组织中TNF-α和IL-1β水平提高(均P<0.05),镜下组织结构明显破坏,肾系数增加。与模型组比较,治疗组以上指标改善(均P<0.05)。结论茶多酚对LPS诱导的AKI保护作用机制与茶多酚对抗氧化应激和抑制肾组织炎症反应有关。

Objective To investigate the effect and mechanism of Tea-polyphenol on lipopolysaccharide (LPS) inducing acute kidney injury of mice.Methods Twenty four male KM mice were randomly divided into 3 groups (n=8):sham group,LPS group and tea-polyphenol +LPS group.Tea-polyphenol +LPS group was given tea-polyphenol solution (200mg/kg in distilled water) once daily.Other groups received same dosage of distilled water once daily.After 7 days,the acute kidney injury model was induced by intraperitoneal injection of LPS(10 mg/kg),the sham group received same dosage of saline instead of LPS.After 8 days,the blood was collected for testing the contents of serum creatinine (Scr),malondialdehyde (MDA),superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) and urea nitrogen (BUN) in serum.Urine levels of urea nitrogen (BUN),urine protein (Pro) and creatinine (Ucr) were measured by corresponding kits.Renal expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by ELISA.HE staining and renal index were employed for determining the damage of renal tissues.Result Compared with sham group,in LPS group,BUN,Scr and MDA in serum increased;SOD and GSH in serum decreased;BUN,Pro and Ucr in urine increased;TNF-α and IL-β expression in renal tissue increased,which also showed typical tissue damage in HE staining slides.Compared with LPS group,above indicators significantly ameliorated in tea-polyphenol +LPS group.Conclusion Tea-polyphenol had protective effect on LPS inducing acute kidney injury from inhibiting oxidative stress and inflammatory reaction in renal tissues.