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首页> 外文期刊>American Journal of Physiology >Compensatory hepatic regeneration after mild, but not fulminant, intraperitoneal sepsis in rats.
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Compensatory hepatic regeneration after mild, but not fulminant, intraperitoneal sepsis in rats.

机译：大鼠轻度但非暴发性腹膜内败血症后的代偿性肝再生。

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摘要

Sepsis is the leading cause of death in surgical intensive care units. Although both mild sepsis secondary to cecal ligation and single puncture (CLP) and fulminant, double puncture CLP (2CLP) may provoke hepatocyte death, we hypothesize that regeneration compensates for cell death after CLP but not 2CLP. In male Sprague-Dawley rats, hepatic necrosis, as determined by serum alpha-glutathione S-transferase (alpha-GST) levels, was significantly but equally elevated over time after both CLP and 2CLP. Apoptosis, evaluated using both terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and morphological examination, was minimal after both CLP and 2CLP. Regeneration, assayed by staining tissue for incorporation of exogenously administered bromodeoxyuridine, was present after CLP but not after 2CLP. To further substantiate impaired regeneration, steady-state levels of mRNAs encoding JunB, LRF-1, and cyclin D1 were determined. After 2CLP, the absence of JunB, LRF-1, and cyclin D1 mRNAs confirmed failed activation of the mitogen-activated protein kinase-linked proliferative pathway and progression through the cell cycle. Therefore, failed hepatocyte regeneration may be a manifestation of hepatic dysfunction in fulminant sepsis.
机译：脓毒症是外科重症监护病房的主要死亡原因。尽管盲肠结扎继发轻度脓毒症和单次穿刺（CLP）和暴发性发作，但两次穿刺CLP（2CLP）可能会引起肝细胞死亡，但我们假设再生能够补偿CLP后的细胞死亡，但不能补偿2CLP。在雄性Sprague-Dawley大鼠中，通过血清α-谷胱甘肽S-转移酶（α-GST）水平确定的肝坏死在CLP和2CLP后均随时间显着升高，但均升高。在同时进行CLP和2CLP处理后，使用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记和形态学检查评估的细胞凋亡极小。 CLP后出现再生，通过组织染色确定是否掺入了外源性溴脱氧尿苷，但在2CLP之后不存在。为了进一步证实受损的再生，测定了编码JunB，LRF-1和细胞周期蛋白D1的mRNA的稳态水平。 2CLP后，JunB，LRF-1和细胞周期蛋白D1 mRNA的缺失证实了丝裂原激活的蛋白激酶相关的增殖途径的激活失败，并且整个细胞周期都没有进展。因此，失败的肝细胞再生可能是暴发性脓毒症中肝功能障碍的表现。

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