新生大鼠内毒素休克时血清TNF-α和NO对心肌超微结构的影响(英文)

Effects of Serum TNF-a and NO on Morphology of Myocardial Tissues in Neonatal Rats with Endotoxic Shock

目的观察新生大鼠内毒素休克时血清TNF-α和NO的动态变化以及与心肌细胞损害的关系,探讨地塞米松(DXM)对心肌的保护作用。方法健康7 d Wistar大鼠17只,随机取9只作实验前基础值组,余108只随机分成对照组、休克组(LPS 5 mg/kg)及治疗组(LPS 5 mg/kg+DXM 5 mg/kg)。各组于注射LPS前(0 h)及注射后2,4,6,24 h分别断头取血并留取心脏组织。双抗夹心ELISA方法测定血清TNF-α浓度,硝酸盐还原酶法测定血清NO浓度,以透射电镜观察心肌超微结构改变。结果①休克组TNF-α于注射LPS2 h达高峰,6 h后下 降到对照组水平。注射LPS 2 h后,DXM组TNF-α高于对照组(P<0.05),但明显低于休克组(P<0.05);注射LPS 4 h,DXM组TNF-α含量低于休克组(P<0.05),但与对照组差异无显著性(P>0.05)。LPS注射后6 h起,3组问TNF-α差异均无显著性(P>0.05)。②休克组血清NO从注射LPS 2 h起升高(P<0.01),24 h达高峰(P<0.01);从注射LPS 2 h起,DXM组血清NO均低于同时间点休克组(P<0.01)。③心肌超微结构改变:休克组于注射LPS 6 h心肌细胞少数线粒体有空泡变性,24 h出现心肌纤维断裂、大量线粒体空泡变性、坏死。而DXM组在注射LPS24 h仅少数线粒体有空泡变性,心肌纤维完整。结论内毒素休克新生大鼠通过释放炎症介质损害心肌组织。

Objective To study the changes of serum TNF-α and NO in neonatal rats with endotoxic shock and its relationship with myocardial cells damge and to explore the protection effect of dexamethasone (DXM) on neonatal rats with endotoxic shock. Methods Nine of the 117 seven-day-old healthy neonatal Wistar rats were used as the pre-experimental base value control group, and the other 108 rats were randomly divided into control group, endotoxic shock group (LPSgroup, LPS 5 nig/kg) and treatment group (DXM group, LPS 5 mg/kg + DXM 5 mg/kg). Before and after injection of LPS (2, 4, 6 and 24 hs), 9 rats in each group were sacrificed and blood samples were collected to detect TNF-a by ELISA and NO by nitrate reductase. Myocardial super-microstructure was observed under an electron microscope. Results ① In the LPS group, the concentration of serum TNF-α peaked at 2 h, and it decreased to the level of control group after 6 hs. In the DXM group, the level of TNF-α at 2 h was higher than that of control group ( P < 0.05), but lower than that of the LPS group ( P < 0.05). At 4 hs the level TNF-α in DXM group was lower than that of the LPS group ( P <0.05), but was not different than that of the control group ( P >0.05). From 6 h after injection, the differences of TNF-α levels in 3 groups were not obvious ( P >0.05). ② In the LPS group, the concentration of NO rose after 2 h ( P <0. 01), and peaked at 24 h ( P <0. 01). After 2 hs, the levels of NO in the DXM group were lower than those of the LPS group ( P < 0.01). ③ Six hours after the injection of LPS, a little mitochondria of myocardial cells in the LPS group appeared to develop vacuolae-like degeneration. At 24 h, most mitochondria of myocardial cells in the LPS group presententecl with vaculea-like degeneration and necrosis. The myocardial fibers were broken. While in the DXM group, the changes in the super-microstructure at 24 h were not as serious as those which talk place in the LPS group. Conclusions TNF-α and No were involved in the damage of myocardial cells in neonatal rats with endotoxic shock. DXM could partly protect the myocardial cells from damage by inhibiting the production of TNF-α and NO.