胰岛素目标血糖管理对脓毒症大鼠肺血管内皮细胞作用的研究

发布时间：2018-03-17 16:08

本文选题：脓毒症　切入点：强化血糖控制　出处：《石河子大学》2013年硕士论文　论文类型：学位论文

【摘要】：目的：观察胰岛素不同目标血糖下对脓毒症大鼠肺血管内皮细胞损伤的影响，探讨胰岛素目标血糖管理对脓毒症肺血管内皮细胞损伤的保护作用及其可能机制。方法：随机将40只SD雄性大鼠分为5组(每组8只)，通过盲肠结扎穿孔术(CLP)法建立大鼠脓毒症模型，按分组进行不同处理：假手术组（sham组）仅做开关腹处理，静脉泵入和其它各组等容量的的生理盐水；CLP组行盲肠结扎穿孔术（cecal ligation and puncture,CLP），静脉泵入和各血糖控制组等容量的生理盐水；各血糖控制组行CLP术，并静脉泵注胰岛素生理盐水溶液，其中A组目标血糖控制在4.4～6.1mmol/L，B组控制在6.2～8.3mmol/L，C组控制在8.4～10.0mmol/L。于造模前后不同时间点运用快速血糖仪检测大鼠的血糖水平(BG)，间隔时间1h，，CLP术后12h处死大鼠。采用双抗夹心ELISA法检测血清TNF-α、ESM-1的表达水平；光镜下观察肺组织形态学变化并行组织病理损伤评分分析；采用免疫组织化学技术检测肺组织中ESM-1的表达水平。结果：CLP组血清TNF-α、ESM-1表达水平明显高于sham组及A、B、C组，差异有统计学差异（P均0.05），A、B、C三组含量均高于sham组（P0.05）；A组TNF-α、ESM-1表达水平较B组和C组明显降低（P均0.05），B组显著低于C组（P0.05）。CLP组及A、B、C组肺组织损伤病理评分均显著高于sham组（P均0.05），而CLP组肺组织病理评分较A、B、C组三组显著增高（P均0.05），其中A组明显小于B组，B组明显小于C组（P均0.05）；sham组肺组织中ESM-1表达水平显著低于CLP组及A、B、C组（P0.05），其中CLP组高表达例数最高，C、B、A组依次降低，ESM-1在CLP组的表达情况与A组比较有显著性差异（P0.05），而与B、C三组之间比较无显著性差异（P0.05）。各组大鼠血清ESM-1水平与血清TNF-1水平、肺组织损伤程度呈显著正相关（P0.01），血清ESM-1表达水平与TNF-α、肺组织损伤程度相关系数分别为0.78、0.79；肺组织ESM-1表达水平与TNF-1、肺组织损伤程度相关系数分别为0.48、0.73；同时血清TNF-α水平与肺组织损伤程度也呈显著正相关，r=0.76（P0.01）。结论： 1．脓毒症时存在肺血管内皮损伤，外周血TNF-α、ESM-1及肺组织ESM-1表达水平升高；随着肺血管内皮损伤程度加重，外周血ESM-1及肺组织ESM-1表达水平增强； 2．经过目标血糖控制脓毒症大鼠肺血管内皮细胞损伤、外周血TNF-α、ESM-1及肺组织ESM-1表达水平显著降低，可能目标血糖控制对TNF-α、ESM-1表达水平有一定的抑制作用，在一定程度对炎症的进展有削弱作用； 3.与6.2～8.3mmol/L及8.4～10.0mmol/L相比，血糖控制在4.4～6.1mmol/L对脓毒症大鼠肺血管内皮细胞损伤的保护作用最为明显。
[Abstract]:Aim: to observe the effects of insulin on pulmonary vascular endothelial cell injury in septic rats and to explore the protective effect of insulin target blood glucose management on pulmonary vascular endothelial cell injury in septic rats and its possible mechanism. Methods: forty Sprague-Dawley male rats were randomly divided into 5 groups (8 rats in each group). Sepsis model was established by cecal ligation and perforation in rats. The caecal ligation and puncture group was given cecal ligation and puncture group, and each blood glucose control group received CLP operation, and insulin saline solution was injected intravenously into each blood glucose control group, while the same volume of normal saline was injected into each blood glucose control group, and the same volume of saline was injected into the blood glucose control group, and the same volume of normal saline was injected into the blood glucose control group, and the blood glucose control group was injected with insulin saline solution. The target blood glucose of group A was controlled at 4.4 卤6.1 mmol 路L ~ (-1) mmol 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) mg 路L ~ (-1) 路L ~ (-1) mg 路L ~ (-1) 路L ~ (-1) mg 路L ~ (-1) 路L ~ (-1) mg 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) mg 路L ~ (-1)? The expression of TNF- 伪 ESM-1 in serum was detected. The morphological changes of lung tissue were observed under light microscope, and the expression of ESM-1 in lung tissue was detected by immunohistochemical technique. Results the expression of TNF- 伪 -ESM-1 in the serum of the patients with sham was significantly higher than that of the patients with sham and ANF- 伪 ESM-1. The expression of TNF- 伪 ESM-1 in sham group was significantly lower than that in group B and C group (P < 0.05). The pathological score of lung tissue injury in group A was significantly higher than that in group sham (P < 0.05), but it was significantly lower in group A than that in group B and group C (P < 0.01), but the expression of TNF- 伪 ESM-1 in group A was significantly lower than that in group B and C (P < 0.05). The pathological scores of lung tissue in group A were significantly higher than those in group B and C (P < 0.01). The histopathological score of lung tissue in CLP group was significantly higher than that in group A and B group (P < 0.05). The expression of ESM-1 in lung tissue of group A was significantly lower than that of group B and group C (P < 0.05), and the expression of ESM-1 in group A was significantly lower than that in group A and group C (P 0.05), and the expression of ESM-1 in group A was significantly lower than that in group A and group B (P < 0.05). The expression of ESM-1 in group A was significantly lower than that in group B and group C (P 0.05). The expression of ESM-1 in CLP group was significantly lower than that in group A (P 0.05), but there was no significant difference between group A and group C (P 0.05). The levels of serum ESM-1 and TNF-1 in each group were significantly lower than those in group A. There was a significant positive correlation between the degree of lung injury and the expression of serum ESM-1 and TNF- 伪, and the correlation coefficient between the expression of ESM-1 and the degree of lung injury was 0.788 ~ 0.79, the correlation coefficient between the expression of ESM-1 and TNF-1, the degree of lung injury was 0.48 ~ 0.73, and the level of serum TNF- 伪 was 0.48 ~ 0.73, respectively. There was also a significant positive correlation with the degree of lung injury. Conclusion:. 1. The expression of TNF- 伪 ESM-1 in peripheral blood and ESM-1 in lung tissue increased with the severity of pulmonary vascular endothelial injury, and the expression level of ESM-1 in peripheral blood and lung tissue increased with the severity of pulmonary vascular endothelial injury, and the expression of TNF- 伪 ESM-1 in peripheral blood and lung tissue increased with the severity of pulmonary vascular endothelial injury. 2. The expression of TNF- 伪 ESM-1 in peripheral blood and ESM-1 in lung tissue of septic rats were significantly decreased after target blood glucose control, which may have some inhibitory effect on the expression of TNF- 伪 -ESM-1 in pulmonary vascular endothelial cells of septic rats. To some extent, it weakens the progress of inflammation; 3.Compared with 8.2 mmol / L and 8.4 卤10.0 mmol / L, the protective effect of blood glucose at 4.4 卤6.1 mmol / L on pulmonary vascular endothelial cell injury was most obvious in septic rats.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R459.7

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