背景:脓毒症常伴有多器官功能障碍,其中心脏损伤的发生率约为60%,与高死亡率密切相关。最近的研究表明高尔基体应激参与肝损伤,肾损伤,和脓毒症的肺损伤。然而,这是否是脓毒症性心肌病(SIC)的关键机制之一尚不清楚。本研究的目的是探讨高尔基应激是否介导SIC及其具体机制。
方法:采用盲肠结扎穿孔法建立雄性C57BL/6J小鼠脓毒症模型。观察高尔基体应激对SIC的影响,小鼠注射高尔基体兴奋剂(BrefeldinA)或高尔基体抑制剂(谷胱甘肽),分别。记录小鼠7天存活率,和心肌损伤指标,包括心功能,心肌酶,心肌病理组织评分,心肌炎症因子,并检测到细胞凋亡。通过免疫荧光观察高尔基体的形态,并通过WB和qPCR检测了高尔基胁迫指数,包括GM-130,GOLPH3和Goligin97。
结果:在CLP之后,小鼠心功能受损,心肌酶水平显著升高。高尔基体应激伴随着心肌炎症和细胞凋亡的增加。此外,形态蛋白GM-130和Golgin97的表达降低,应激蛋白GOLPH3的表达增加。此外,BrefeldinA增加小鼠的7天死亡率和上述指标。谷胱甘肽的使用改善了所有上述指标。
结论:高尔基应激介导SIC,抑制高尔基体应激可以通过抑制细胞凋亡和炎症反应来改善SIC。
BACKGROUND: Sepsis is often accompanied by multiple organ dysfunction, in which the incidence of cardiac injury is about 60%, and is closely related to high mortality. Recent studies have shown that Golgi stress is involved in liver injury, kidney injury, and lung injury in sepsis. However, whether it is one of the key mechanisms of sepsis-induced cardiomyopathy (SIC) is still unclear. The aim of this study is to investigate whether Golgi stress mediates SIC and the specific mechanism.
METHODS: Sepsis model of male C57BL/6J mice was established by cecal ligation and puncture. To observe the effect of Golgi stress on SIC, mice were injected with Golgi stimulant (Brefeldin A) or Golgi inhibitor (Glutathione), respectively. The 7-day survival rate of mice were recorded, and myocardial injury indicators including cardiac function, myocardial enzymes, myocardial pathological tissue score, myocardial inflammatory factors, and apoptosis were detected. The morphology of Golgi was observed by immunofluorescence, and the Golgi stress indices including GM-130, GOLPH3 and Goligin97 were detected by WB and qPCR.
RESULTS: After CLP, the cardiac function of mice was impaired and the levels of myocardial enzymes were significantly increased. Golgi stress was accompanied by increased myocardial inflammation and apoptosis. Moreover, the expressions of morphological proteins GM-130 and Golgin97 were decreased, and the expression of stress protein GOLPH3 was increased. In addition, Brefeldin A increased 7-day mortality and the above indicators in mice. The use of glutathione improves all of the above indicators.
CONCLUSIONS: Golgi stress mediates SIC, and the inhibition of Golgi stress can improve SIC by inhibiting apoptosis and inflammation.