A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury.
A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury.
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阻断Toll样受体信号转导的细胞穿透肽保护肾脏免受缺血再灌注损伤。
DOI：
10.3390/ijms22041627
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发表时间：
2021-02-05
影响因子：
5.6
通讯作者：
Lee SH
中科院分区：
文献类型：
--
作者：
Jung SW;Seo JW;Park SH;Kim YG;Moon JY;Choi S;Lee SH
肾缺血-再灌注损伤（IRI）涉及大多数表现为肾功能恶化的临床病症;然而，针对这种类型的损伤的特异性治疗仍然远离临床使用。由于Toll样受体（TLR）介导的信号传导是IRI的关键介质，我们研究了一种名为TLR抑制肽1（TIP 1）的多TLR阻断肽对肾脏IRI的作用，该肽对TLR 4的作用最强。我们对C57 BL/6小鼠进行23分钟的肾蒂夹闭，然后腹膜内注射载体或TIP 1。假手术对照小鼠仅进行侧腹切口。再灌注24小时后收获小鼠肾脏进行组织学、蛋白质印迹、RT-PCR和流式细胞术分析。用TIP 1预处理降低了升高的血浆肌酐水平的幅度并减弱了肾小管损伤。TIP 1治疗还减少了缺血后肾脏中炎性细胞因子的mRNA表达，并减少了凋亡细胞和氧化应激。在用TIP 1预处理的肾脏中，巨噬细胞和辅助性T细胞17的浸润比仅IRI组中的那些少。这些结果表明，TIP 1在减轻IRI诱导的肾损伤程度方面具有潜在的有益作用。
Renal ischemia-reperfusion injury (IRI) is involved in the majority of clinical conditions that manifest as renal function deterioration; however, specific treatment for this type of injury is still far from clinical use. Since Toll-like receptor (TLR)-mediated signaling is a key mediator of IRI, we examined the effect of a multiple-TLR-blocking peptide named TLR-inhibitory peptide 1 (TIP1), which exerts the strongest action on TLR4, on renal IRI. We subjected C57BL/6 mice to 23 min of renal pedicle clamping preceded by intraperitoneal injection with a vehicle or TIP1. Sham control mice underwent flank incision only. Mouse kidneys were harvested after 24 h of reperfusion for histology, western blot, RT-PCR, and flow cytometry analysis. Pretreatment with TIP1 lowered the magnitude of elevated plasma creatinine levels and attenuated tubular injury. TIP1 treatment also reduced mRNA expression of inflammatory cytokines and decreased apoptotic cells and oxidative stress in post-ischemic kidneys. In kidneys pretreated with TIP1, the infiltration of macrophages and T helper 17 cells was less abundant than those in the IRI only group. These results suggest that TIP1 has a potential beneficial effect in attenuating the degree of kidney damage induced by IRI.
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TAK-242 是 Toll 样受体 4 的拮抗剂，可预防小鼠急性脑缺血/再灌注损伤。
DOI：
10.1038/jcbfm.2014.240
发表时间：
2015-03-31
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
--
影响因子：
3
作者：
Hu GH;Duan L;Jiang M;Zhang CL;Duan YY
通讯作者：
Duan YY
影响因子：
19.6
作者：
Han SJ;Williams RM;D'Agati V;Jaimes EA;Heller DA;Lee HT
通讯作者：
Lee HT
影响因子：
4.4
作者：
Shigeoka, Alana A.;Holscher, Todd D.;McKay, Dianne B.
通讯作者：
McKay, Dianne B.
影响因子：
19.6
作者：
Chen, Jianlin;John, Reji;Richardson, James A.;Shelton, John M.;Zhou, Xin J.;Wang, Yanxia;Wu, Qing Qing;Hartono, John R.;Winterberg, Pamela D.;Lu, Christopher Y.
通讯作者：
Lu, Christopher Y.