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茶多酚通过抑制 TLR4/NF-κB p65 信号通路的激活对肾缺血/再灌注损伤的保护作用。

Protective effect of tea polyphenols on renal ischemia/reperfusion injury via suppressing the activation of TLR4/NF-κB p65 signal pathway.

机构信息

Department of Nephrology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.

Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin 300060, China.

出版信息

Gene. 2014 May 25;542(1):46-51. doi: 10.1016/j.gene.2014.03.021. Epub 2014 Mar 12.

Abstract

Tea polyphenols (TP) was investigated in rats for its protective effect on renal ischemia/reperfusion injury (RIRI). Rats were randomized into groups as follows: (I) sham group (n=10); (II) RIRI group (n=10); (III) RIRI+TP (100mg/kg) group (n=5); (IV) RIRI+TP (200mg/kg) group (n=5); (V) RIRI+TP+ Astragalus mongholicus aqueous extract (AMAE) (300 mg/kg+100mg/kg) group (n=5). For the IRI+TP groups, rats were orally given with tea polyphenols (100, 200 and 300 mg/kg body weight) once daily 10 days before induction of ischemia, followed by renal IRI. For the sham group and RIRI group, rats were orally given with equal volume of saline once daily 10 days before induction of ischemia, followed by renal IRI. Results showed that tea polyphenol pretreatment significantly suppressed ROS level and MDA release. On the other hand, in rats subjected to ischemia-reperfusion, the activities of endogenous antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) showed recovery, whereas the levels of urea nitrogen and serum creatinine were reduced by administration of tea polyphenols orally for 10 days prior to ischemia-reperfusion. Moreover, tea polyphenol pretreatment significantly decreased TLR4 and NF-κB p65 protein expression levels in RIRI rats. At the same time, tea polyphenol pretreatment attenuated the increased level of serum IL-1β, IL-6, ICAM-1 and TNF-α, and enhanced IL-10 production in RIRI rats. Furthermore, tea polyphenol pretreatment significantly decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion, alleviating renal ischemia/reperfusion injury. These results cumulatively indicate that tea polyphenol pretreatment could suppress the TLR4/NF-κB p65 signaling pathway, protecting renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis, which implies that antioxidants may be a potential and effective agent for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by TLR4/NF-κB p65 signal pathway. Moreover, supplement of AMAE can increased renal protection effect of TP.

摘要

茶多酚(TP)在大鼠中被研究其对肾缺血/再灌注损伤(RIRI)的保护作用。大鼠随机分为以下几组:(I)假手术组(n=10);(II)RIRI 组(n=10);(III)RIRI+TP(100mg/kg)组(n=5);(IV)RIRI+TP(200mg/kg)组(n=5);(V)RIRI+TP+黄芪水提物(AMAE)(300mg/kg+100mg/kg)组(n=5)。对于 RIRI+TP 组,大鼠在缺血诱导前 10 天每天口服给予茶多酚(100、200 和 300mg/kg 体重),然后进行肾缺血/再灌注。对于假手术组和 RIRI 组,大鼠在缺血诱导前 10 天每天口服给予等容量生理盐水,然后进行肾缺血/再灌注。结果表明,茶多酚预处理显著抑制 ROS 水平和 MDA 释放。另一方面,在缺血再灌注大鼠中,内源性抗氧化酶的活性,包括超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽还原酶(GR)和谷胱甘肽过氧化物酶(GSH-Px),在口服给予茶多酚 10 天后得到恢复,而尿素氮和血清肌酐的水平则降低。此外,茶多酚预处理显著降低了 RIRI 大鼠 TLR4 和 NF-κB p65 蛋白表达水平。同时,茶多酚预处理可降低 RIRI 大鼠血清中 IL-1β、IL-6、ICAM-1 和 TNF-α水平的升高,并增加 IL-10 的产生。此外,茶多酚预处理可显著减少肾缺血/再灌注诱导的肾小管上皮细胞凋亡,减轻肾缺血/再灌注损伤。这些结果表明,茶多酚预处理可抑制 TLR4/NF-κB p65 信号通路,保护肾小管上皮细胞免受缺血/再灌注诱导的细胞凋亡,这表明抗氧化剂可能通过抑制 TLR4/NF-κB p65 信号通路诱导的细胞外凋亡信号通路,成为预防缺血/再灌注损伤的一种潜在有效药物。此外,补充黄芪可增强茶多酚的肾保护作用。

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