Abstract

Purpose

Many proteins in tripartite motif (TRIM) family have been reported to play an important role in cerebral ischemia/reperfusion (I/R) injury. This study was designed to investigate the effect of TRIM14 on the cerebral I/R injury in rats.

Methods

The rat model was constructed through inserting thread into the middle cerebral artery. The expression of TRIM14 was measured by qRT-PCR, immunoblotting, and immunofluorescence. The hippocampal sections were stained with 2,3,5-triphenyltetrazolium chloride (TTC) to determine infarct volume and used for measuring the neurologic deficit score and brain water content. The H&E staining was used for immunohistochemical (IHC) staining. The number of apoptotic cells was measured by fluorescence microscopy. The levels of IL-6, IL-1β, and TNFα were detected by qRT-PCR and ELISA. The swimming speed, latency time, and number of platform crossings were measured by the water maze test.

Results

TRIM14 was significantly enhanced in rats with cerebral I/R injury compared to Sham rats, showing its highest level at 24 h after I/R. TRIM14 inhibition reduced ischemic brain injury, suppressed neuron apoptosis, suppressed inflammation, and improved cognitive dysfunction in rats with cerebral I/R injury. TRIM14 inhibition also suppressed the activation of NF-κB/NLRP3 pathway in rats with cerebral I/R injury.

Conclusion

In conclusion, the expression of TRIM14 was increased in rats with cerebral I/R injury, the protective effect of TRIM14 inhibitor on cerebral I/R injury in rats depends on its anti-apoptotic and anti-inflammatory effect. The underlying mechanism was, at least partially, through regulating NF-κB/NLRP3 pathway.

中文翻译：

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抑制 TRIM14 通过调节 NF-κB/NLRP3 通路介导的炎症和细胞凋亡来保护脑缺血/再灌注损伤

摘要

目的

据报道，三方基序 (TRIM) 家族中的许多蛋白质在脑缺血/再灌注 (I/R) 损伤中起重要作用。本研究旨在研究 TRIM14 对大鼠脑 I/R 损伤的影响。

方法

通过将线插入大脑中动脉构建大鼠模型。通过 qRT-PCR、免疫印迹和免疫荧光测量 TRIM14 的表达。海马切片用2,3,5-三苯基四唑氯化物（TTC）染色以确定梗死体积并用于测量神经功能缺损评分和脑含水量。H&E 染色用于免疫组织化学 (IHC) 染色。通过荧光显微镜测量凋亡细胞的数量。通过qRT-PCR和ELISA检测IL-6、IL-1β和TNFα的水平。通过水迷宫测试测量游泳速度、潜伏时间和平台穿越次数。

结果

与 Sham 大鼠相比，TRIM14 在脑 I/R 损伤大鼠中显着增强，在 I/R 后 24 小时显示其最高水平。TRIM14 抑制可减轻脑 I/R 损伤大鼠的缺血性脑损伤、抑制神经元凋亡、抑制炎症并改善认知功能障碍。TRIM14 抑制还抑制了脑 I/R 损伤大鼠 NF-κB/NLRP3 通路的激活。

结论

综上所述，TRIM14在脑I/R损伤大鼠中表达上调，TRIM14抑制剂对大鼠脑I/R损伤的保护作用取决于其抗凋亡和抗炎作用。潜在机制至少部分是通过调节 NF-κB/NLRP3 途径。