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

摘要:

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（10?mg/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（200?mg/kg，1次/d），其他两组均用等量蒸馏水灌胃，1次/d，持续8?d。复制模型24?h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24?h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。

Abstract:

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 (200?mg/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.