脓毒血症过程肝脏结构和功能关系的研究  

The research of hepatic configuration and function in septicemic rat

作　　者：吴红红[1] 高继玲[1] 张建龙[2] 王红梅[2] 玛依努尔.伊明尔艾山 

机构地区：[1]新疆医科大学附属中医医院肾病科 [2]新疆医科大学基础医学院生理学教研室,新疆乌鲁木齐830000

出　　处：《新疆医科大学学报》2006年第12期1152-1155,共4页Journal of Xinjiang Medical University

摘　　要：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 study the relation of TNF and hepatic apoptosis, and the effect of glucocorticoid （GC） on them in order to know the machnism of descrease of liver function and of interference of GC in sepatic rat. Methods： 24 Wistar rats were randomly divided into control group （n =6）, septic group （n = 12） and interference group （n =6）. The septicemic group was divided into 2 groups of 60, 180 rain after cecal ligation and puncture （CLP）. The interference group was given GC （5 mg/kg）immediately after CLP. Serum and liver tissure TNF-α and Bcl-2 protein levels and hepatic apoptosis were measured at various intervals. At the same time AST and ALT were also determined. Results： TNF protein levels were significantly elevated in CLP compared to normal control in liver tissure （P 〈0.01）, but there was not a noble discrep ancy between 30 min and 60 rain （P 〉0.05）, which reached the top at 180 min. The change of TNF-α protein in serum was consisted with in tissue. In addition the number of hepatic apoptosis was higher in CLP than in control group （P 〈0.01） and progressively increased （P 〈0. 01）. The index of hepatic apoptosis was consisted with TNF α protein too. Bcl-2 protion expression was less after CLP compared to TNF-α protein, and there was a discrepancy compared to control group （P 〈0.01）. Meanwhile, the level of serum ALT were markedly increased compared to normal control （all P 〈0.01）, but AST was noble higher at 120 rain and 180 rain after CLP （P 〈0.01）. Under the electron microscope, different morphological disorders of hepatocytes and hepatic sinusoid endothelial cells were observed, mitochondria swelled, apoptosis in CLP 120 min group and CLP 180 min group. But the parameters were lower in therapy group. Conlusions： The effect of serum and liver tissue TNF-α was elevated progressively, which depressed the Bcl-2 protein expression and induced hepatic apoptosis through signal conduction in CLP-induced sepsis. And the liver function

关 键 词：脓毒血症 TNF—α 肝细胞凋亡 BCL-2 糖皮质激素 

分 类 号：R631.2[医药卫生—外科学] R322.47[医药卫生—临床医学]