The Role of Thioredoxin-1 in Suppression Sepsis Through Inhibiting Mitochondrial-Induced Apoptosis in Spleen
The Role of Thioredoxin-1 in Suppression Sepsis Through Inhibiting Mitochondrial-Induced Apoptosis in Spleen
复制标题
硫氧还蛋白-1 通过抑制脾脏线粒体诱导的细胞凋亡来抑制脓毒症
DOI：
10.1097/shk.0000000000000789
复制
发表时间：
2017-06-01
期刊：
影响因子：
3.1
通讯作者：
Bai, Jie
中科院分区：
文献类型：
--
作者：
Chen, Guobing;Li, Xiang;Bai, Jie
脓毒症是一个严重的公共卫生问题，是重症监护病房中危重患者死亡的主要原因。硫氧还蛋白 -1（Trx -1）是一种调节氧化还原的蛋白质，也是炎症和细胞凋亡的调节剂。我们之前的研究报道，在实验性脓毒症模型中，Trx -1减少了内质网介导的肺部炎症。然而，其对脾脏中线粒体介导的细胞凋亡的影响尚未见报道。我们研究了Trx -1是否能预防脓毒症中脾脏细胞的凋亡。在本研究中，我们发现与野生型小鼠相比，在盲肠结扎穿孔（CLP）诱导的脓毒症中，Trx -1过表达转基因（Tg）小鼠脾脏中的细胞凋亡减少。CLP术后12小时，Trx -1 Tg小鼠腹腔菌落形成单位以及血浆中降钙素原水平显著降低。脾脏中c - jun - N - 末端激酶、Bax、caspase - 9和caspase - 3的表达增加，而在Trx -1 Tg小鼠中这些表达受到抑制。然而，脓毒症中降低的Bcl - 2表达在Trx -1 Tg小鼠中得以恢复。我们的研究结果表明，Trx -1的过表达通过抑制脾脏中线粒体诱导的细胞凋亡途径来提供对脓毒症的保护。这项研究可能为临床干预提供一个新的靶点，以及治疗脓毒症的潜在策略。
Sepsis is a serious public health issue and the leading cause of death in critically ill patients in intensive care units. Thioredoxin-1 (Trx-1) is a protein of regulating redox, as well as a modulator of inflammation and apoptosis. Our previous study reported that Trx-1 decreased endoplasmic reticulum-mediated inflammation involved in lung in a model of experimental sepsis. However, its effect on mitochondrial-mediated apoptosis in spleen has not been reported. We studied whether Trx-1 could prevent spleen cells apoptosis in sepsis. In the present study, we showed that the apoptosis in spleen was decreased in sepsis induced by cecal ligation and puncture (CLP) in Trx-1 overexpression transgenic (Tg) mice compared with wild-type mice. Colony forming units in the peritoneal cavity and the level of procalcitonin in plasma were significantly decreased in Trx-1 Tg mice 12h after CLP. The expressions of c-jun-N-terminal kinase, Bax, caspase-9, and caspase-3 were increased in spleen, which were suppressed in Trx-1 Tg mice. However, the decreased Bcl-2 expression in sepsis was recovered in Trx-1 Tg mice. Our results suggest that overexpression of Trx-1 provides protection against sepsis through suppressing mitochondria-induced apoptosis pathway in spleen. This study may provide a new target for clinical intervention, as well potential strategies for treatment of sepsis.