胰岛素在急性肺损伤中的作用和机制研究

发布时间：2018-03-31 11:29

本文选题：胰岛素　切入点：急性肺损伤　出处：《中南大学》2012年硕士论文

【摘要】：目的：研究胰岛素(ISL)在脂多糖(LPS)诱导的急性肺损伤(ALI)中的治疗作用及其相关机制。方法：将72只雄性SD大鼠随机分为9组,分别为正常对照组、造模组(LPS注射后2h、6h、12h、24h组)、治疗组(LPS注射后2h、6h、12h、24h组)。各组均将尾静脉注射LPS的时间列为实验时间点“0”,造模组尾静脉注射LPS4mg/kg,治疗组在LPS注射前2h腹部皮下注射中效胰岛素4U/kg,正常对照组在相应时间和相同部位注射等量生理盐水。按时取血标本测定血糖水平、ELISA法测定血清C肽和肺组织匀浆TNF-α浓度、免疫组织化学法检测肺组织中MMP-9和TIMP-1表达；同时检测肺湿干重比(W/D)和肺组织病理变化情况。结果： 1、与正常对照组相比较,尾静脉注射LPS4mg/kg后约1小时,SD大鼠出现不同程度的烦躁不安、呼吸急促、活动减少、反应迟钝等表现；2小时后肺W/D增高、肺间质水肿、中性粒细胞浸润、弥漫性毛细血管扩张、肺泡腔出血、部分肺泡萎陷或肺实变及气肿等肺组织急性炎性病理改变,提示采用LPS成功复制了ALI动物模型。 2、造模组大鼠的血糖和血C肽水平变化呈现相同的趋势,注射LPS后2h升高,12h达到最高,之后下降但仍显著高于正常,提示LPS诱导的ALI存在胰岛素抵抗现象。 3、造模组大鼠在注射LPS后2h肺组织匀浆TNF-α水平开始升高,6h达高峰,之后逐渐下降,24h时仍高于正常对照组(P0.05)；其肺组织中MMP-9和TIMP-1表达增高且变化趋势相同,2h升高,12h达高峰,24h时下降但仍高于正常对照组(P0.05)。 4、与造模组相比较,治疗组大鼠病情严重程度和肺组织病理损伤程度明显减轻,血糖和C肽水平下降,肺组织匀浆TNF-α和肺组织MMP-9表达水平显著下降,而肺组织TIMP-1表达增高、MMP-9/TIMP-1比值下降。结论： (1)脂多糖诱导的大鼠急性肺损伤存在胰岛素抵抗现象。 (2)胰岛素治疗有助于减轻脂多糖所致的急性肺损伤,其机制可能与其对抗胰岛素抵抗现象、及降低TNF-α水平、减少MMP-9表达、升高TIMP-1表达有关、使MMP-9/TIMP-1体系趋于平衡。
[Abstract]:Objective:. To study the therapeutic effect of insulin ISL on acute lung injury induced by lipopolysaccharide (LPS) and its related mechanism. Methods:. Seventy-two male SD rats were randomly divided into 9 groups as normal control group. The rats in the model group were divided into two groups: 2 h, 6 h, 12 h and 24 h after LPS injection, and 2 h, 6 h, 12 h and 24 h after LPS injection, respectively. The time of intravenous injection of LPS was classified as "0" in each group. The model group was injected with LPS4 mg / kg / L 2 h before LPS injection, and insulin was subcutaneously injected in the treatment group 2 hours before LPS injection. 4U / kg, the normal control group was injected with the same amount of normal saline at the corresponding time and the same part. The blood glucose level was measured by Elisa and the concentration of serum C peptide and lung homogenate TNF- 伪 were determined by Elisa. The expression of MMP-9 and TIMP-1 in lung tissue was detected by immunohistochemical method, and the lung wet / dry weight ratio (WR) and pathological changes of lung tissue were also detected. Results:. 1Compared with the normal control group, the SD rats had different degrees of restlessness, shortness of breath, decreased activity, slow response and so on at 1 hour after LPS4mg/kg injection. After 2 hours, the lung W- / D increased, pulmonary interstitial edema and neutrophil infiltration were observed in SD rats. Diffuse capillary dilatation, alveolar cavity hemorrhage, partial alveolar collapse or pulmonary consolidation, emphysema and other acute inflammatory pathological changes of lung tissue, which indicated that the animal model of ALI was successfully reproduced by LPS. 2. The changes of blood glucose and C-peptide levels in the model group showed the same trend, and reached the highest at 2 h after LPS injection, then decreased significantly but still significantly higher than normal, suggesting that ALI induced by LPS had insulin resistance. 3. The TNF- 伪 level of lung homogenate in the model group began to increase at 2 h after injection of LPS and reached the peak at 6 h. After 24 hours, the expression of MMP-9 and TIMP-1 in the lung tissue of the control group was still higher than that of the normal control group, and the expression of MMP-9 and TIMP-1 in the lung tissue increased at 12 h and reached the peak at 12 h, but was still higher than that of the normal control group at 24 h, but still higher than that of the normal control group. 4Compared with the model group, the severity of the disease and the degree of pathological injury of lung tissue in the treatment group were obviously alleviated, the levels of blood glucose and C-peptide were decreased, and the expression of TNF- 伪 and MMP-9 in the lung homogenate was significantly decreased in the treatment group. However, the ratio of MMP-9 / TIMP-1 decreased when the expression of TIMP-1 in lung tissue increased. Conclusion:. 1) Insulin resistance was found in acute lung injury induced by lipopolysaccharide in rats. 2) Insulin therapy can alleviate acute lung injury induced by lipopolysaccharide, and its mechanism may be related to its resistance to insulin resistance, decrease of TNF- 伪 level, decrease of MMP-9 expression, increase of TIMP-1 expression, and balance of MMP-9/TIMP-1 system.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R563.8

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