持续胰岛素输注对脓毒症早期大鼠肝脏线粒体的保护作用

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目的:探讨持续胰岛素输注对脓毒症早期大鼠肝脏线粒体是否具有保护作用及其作用机制。方法:SD大鼠24只随机分为正常对照组(n=8)、LPS组(n=8)和胰岛素干预组(n=8)。监测各组大鼠的血糖水平及腹腔注射后2h和6h的血清TNF-α和IL-6水平;运用流式细胞术检测24h时点分离肝脏线粒体的膜电位;检测测分离肝脏线粒体SOD和MDA水平;电镜观察24h肝脏线粒体形态学变化。结果:LPS组在腹腔注射LPS后各监测时点,血糖水平较正常对照组均显著升高,并且注射后2h和6h的血清TNF-α和IL-6水平较正常对照组显著升高。与正常对照组相比,LPS组24h肝脏线粒体膜电位显著下降,线粒体SOD水平显著升高,而MDA水平则变化不显著。胰岛素干预组与LPS组比较,血糖水平、TNF-α及IL-6和肝脏线粒体SOD水平均显著降低,而肝脏线粒体膜电位则显著升高,线粒体MDA水平则改变不显著。肝脏线粒体超微结构改变尚不明显,LPS组与正常对照组相比,仅个别线粒体出现空泡样改变,部分基质凝固;而胰岛素干预组则未见空泡样改变。结论:脓毒症早期大鼠肝脏线粒体存在可逆性损伤;持续胰岛素输注对脓毒症早期大鼠肝脏线粒体有明显的保护作用,此保护作用可能与其减轻过度的炎症反应和降低过高的血糖水平有关。 Objective: To investigate whether continuous insulin infusion protects the mitochondria of rat liver from early sepsis and its mechanism. Methods: Twenty-four SD rats were randomly divided into normal control group (n = 8), LPS group (n = 8) and insulin intervention group (n = 8). The levels of serum TNF-α and IL-6 were measured at 2 h and 6 h after intraperitoneal injection. The mitochondrial membrane potential of liver was detected by flow cytometry at 24 h. The mitochondrial SOD and MDA Level; 24h electron microscope observation of mitochondria morphological changes. Results: After LPS injected into LPS group, the levels of blood glucose and blood sugar in each group were significantly higher than those in normal control group, and the levels of TNF-α and IL-6 in 2 and 6 hours after LPS injection were significantly higher than those in normal control group. Compared with the normal control group, the mitochondrial membrane potential of liver in LPS group decreased significantly, the level of mitochondrial SOD increased significantly, but the level of MDA did not change significantly. Insulin intervention group compared with LPS group, blood glucose, TNF-α and IL-6 and liver mitochondrial SOD levels were significantly lower, while the liver mitochondrial membrane potential was significantly increased, mitochondrial MDA levels were not significantly changed. The ultrastructural changes of liver mitochondria are not obvious. Compared with the normal control group, only some mitochondria of the LPS group showed vacuolar changes and part of the matrix solidified; while the insulin-treated group showed no vacuole-like changes. CONCLUSION: In the early stage of sepsis, there is reversible damage to the mitochondria in rat liver. Continuous infusion of insulin significantly protects the mitochondria in rat liver from early sepsis. This protective effect may be related to its reduction of excessive inflammatory reaction and decrease of excessive blood glucose Horizontal related.
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