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目的:研究脓毒血症时肝脏功能降低的机制及糖皮质激素的作用机制。方法:将24只雄性Wistar大鼠随机分为4组,其中6只作为对照组,另外18只采用盲肠结扎穿孔术(CLP)致脓毒血症模型,其中12只于术后60、180min时限又分为2组作实验组,另6只于术后即给予糖皮质激素地塞米松(5 mg/kg)作为干预组。各组均测定肝组织TNF-α和Bcl-2蛋白表达及肝细胞凋亡的情况,同时测定肝脏功能的变化。结果:CLP术后肝组织中TNF-α水平持续升高,与对照组相比有统计学差异(P<0.01)。血清TNF-α含量变化与肝组织TNF-α的表达具有一致性。CLP术后肝细胞凋亡数目与对照组相比有统计学差异,并呈进行性增加(P<0.01)。肝细胞的凋亡数目与肝组织TNF-α的表达也呈现一致性。CLP术后肝组织Bcl-2蛋白与TNF-α蛋白相比表达较弱,但与对照组仍有统计学差异(P<0.01)。血浆中ALT/AST呈异常改变,同时术后肝脏组织结构紊乱。结论:由CLP所致的脓毒血症过程中,肝脏组织TNF-α蛋白的表达和血浆中TNF-α蛋白的含量进行性增加,通过激活促细胞凋亡的程序,相对抑制抗凋亡蛋白Bcl-2的表达而诱导肝细胞凋亡。与肝脏结构受损、功能下降是一致的。早期应用地塞米松处理脓毒血症对肝脏有一定的保护作用,其机制可能是抑制了脓毒血症早期细胞因子TNF-α的释放,以及由此导致的细胞凋亡的发生。
OBJECTIVE: To investigate the mechanism of hepatic dysfunction and the mechanism of action of glucocorticoids in sepsis. Methods: Twenty-four male Wistar rats were randomly divided into 4 groups, of which 6 were used as the control group and the other 18 were induced by cecal ligation and puncture (CLP). 12 of them were in the 60,180 min Divided into two groups for the experimental group, the other six were given glucocorticoid dexamethasone (5 mg / kg) as the intervention group. The expression of TNF-α and Bcl-2 in hepatocytes and the apoptosis of hepatocytes were detected in each group, and the changes of hepatic function were also measured. Results: The level of TNF-αin the liver of CLP continued to increase, which was significantly different from the control group (P <0.01). The change of serum TNF-α content was consistent with the expression of TNF-α in liver tissue. The number of apoptotic hepatocytes in CLP was significantly higher than that in control group (P <0.01). The number of apoptotic hepatocytes and the expression of TNF-α in liver tissue also showed consistency. The expression of Bcl-2 protein in liver tissue was lower than that of TNF-α protein in CLP group, but still no significant difference compared with control group (P <0.01). Plasma ALT / AST showed abnormal changes, while liver tissue disorder. CONCLUSIONS: During the course of sepsis induced by CLP, the expression of TNF-α in liver tissue and the content of TNF-α in plasma increased progressively. By activating the pro-apoptotic program, the anti-apoptotic protein Bcl-2 expression induced apoptosis of hepatocytes. Impaired liver structure, function decline is consistent. Early application of dexamethasone to treat sepsis has a protective effect on the liver, and its mechanism may be to inhibit the release of cytokines TNF-α early sepsis and the resulting apoptosis.