艾司洛尔对脓毒症大鼠肺脏和肠道保护作用的实验研究
发布时间：2018-08-06 19:00
【摘要】：目的(1)研究短效β1受体阻滞剂艾司洛尔对脓毒症大鼠肺损伤的保护作用,并探讨其机制;(2)研究短效β1受体阻滞剂艾司洛尔对脓毒症大鼠肠道损伤的保护作用。方法72只SD雄性大鼠,随机分为假手术组(Sham组)、脓毒症组(CLP组)和艾司洛尔组(ES组)。各组随机抽取6只大鼠观察7天生存情况,剩余18只大鼠又随机分为6h、12h和24h三个亚组,每个亚组6只。Sham组采用盲肠探查术,CLP和ES组均采用盲肠结扎穿孔(CLP)法建立脓毒症模型。造模成功后均行左侧颈内静脉置管,Sham和CLP组持续微量泵泵入生理盐水1ml/h,共计6h;ES组持续泵入艾司洛尔稀释液1ml/h(15mg/kg/h),共计6h。各亚组于造模成功后6h、12h及24h后处死大鼠采集标本,采用ELISA法检测血浆CA、TNF-α水平、肺组织NF-κB水平、肠道组织DAO、i-FABP水平。采用Western Blot法检测肺组织TLR4、NF-κB蛋白表达水平。测量肺组织湿干重比率、肺系数、水含量,行左肺肺泡灌洗,测定灌洗液中蛋白含量。光学显微镜下观察肺、肠道组织病理变化。结果(1)术后6h,CLP、ES组血清CA水平与Sham组相比明显升高,具有显著差异性(P0.05),且ES组CA水平比CLP组明显升高(P0.05)。术后12h,ES组CA水平与Sham组相比仍明显升高(P0.05);术后24h,ES组CA水平与CLP组相比明显升高(P0.05)。(2)术后6h、12h、24h,CLP、ES组肺组织NF-κB水平明显升高,与Sham组相比差异有统计学意义(P0.05),且各时间点ES组NF-κB水平也均比CLP组明显降低(P0.05)。(3)Western Blot结果显示,术后6h、12h、24h,CLP组、ES组TLR4、NF-κB蛋白表达明显增高,与Sham组相比差异有统计学意义(P0.05),且各时间点ES组TLR4、NF-κB蛋白表达均比CLP组明显降低(P0.05)。(4)术后6h、12h、24h,CLP、ES组血清TNF-ɑ水平与Sham组相比明显升高,具有显著差异性(P0.05),且各时间点ES组TNF-ɑ水平也均比CLP组明显降低(P0.05)。(5)术后6h、12h、24h,CLP组、ES组肺组织湿重/干重、肺系数、肺水含量、肺泡灌洗液蛋白含量水平与Sham组相比均明显升高(p0.05),且各时间点ES组肺组织湿重/干重、肺系数、肺水含量、肺泡灌洗液蛋白含量水平也均较CLP组明显降低(p0.05)。(6)术后6h、12h、24h,CLP、ES组肠道组织DAO水平明显降低,与Sham组相比差异有统计学意义(P0.05),且各时间点ES组DAO水平也均比CLP组明显升高(P0.05)。(7)术后6h、12h、24h,CLP、ES组肠道组织i-FABP水平明显降低,与Sham组相比差异有统计学意义(P0.05),且各时间点ES组i-FABP水平也均比CLP组明显升高(P0.05)。(8)肺组织病理形态学改变:Sham组病理损伤程度最轻,CLP组病理损伤程度最重,ES组各时间点病理损伤均较CLP组明显减轻,较Sham组明显加重。(9)肠道组织病理形态学改变:Sham组病理损伤最轻,CLP组病理损伤程度最重,ES组各时间点病理损伤均较CLP组明显减轻,较Sham组明显加重。(10)艾司洛尔能延长脓毒症大鼠生存时间。结论脓毒症早期机体交感神经兴奋,释放大量儿茶酚胺,激活炎症因子,导致肺脏、肠道损伤。艾司洛尔通过促进儿茶酚胺分泌,抑制炎症因子释放,降低肺脏及肠道的通透性,减轻肺水肿,保护肠粘膜屏障,进而起到保护肺脏和肠道的作用。其机制可能为艾司洛尔改善β受体对儿茶酚胺的反应性,通过抑制TLR4—NF-κB—TNF-α炎症信号通路来调节炎症因子水平,从而发挥对肺脏的保护作用。通过抑制炎症因子水平,从而发挥对肠道的保护作用。
[Abstract]:Objective (1) to study the protective effect of short effect beta 1 receptor blocker, esmolol, on pulmonary injury in septic rats and explore its mechanism. (2) study the protective effect of short effect beta 1 receptor blocker, esmolol, on the intestinal injury of sepsis rats. Methods 72 SD male rats were randomly divided into sham operation group (group Sham), sepsis group (group CLP) and esmolol. Group (group ES). 6 rats were randomly selected to observe 7 days of survival. The remaining 18 rats were randomly divided into 6h, 12h and 24h subgroups, 6.Sham groups in each subgroup were treated with cecum, and both CLP and ES groups were established by cecal ligation and perforation (CLP). The left internal jugular vein was performed after the model was successfully established. Sham and CLP groups continued. The micropump was pumped into the physiological saline 1ml/h, a total of 6h, and the ES group was pumped into the esmolol diluent 1ml/h (15mg/kg/h). All the subgroups of 6h. were executed after 6h, 12h and 24h were executed after the model success. The CA of plasma, the level of TNF- alpha, the level of lung tissue and the level of the intestinal tissue were detected by ELISA method. TLR4, NF- kappa B protein expression level. Measurement of wet dry weight ratio of lung tissue, lung coefficient, water content, left lung alveolar lavage, the determination of the protein content in the lavage fluid. The lung and intestinal histopathological changes were observed under optical microscope. Results (1) the serum CA level in 6h, CLP, ES group after operation was significantly higher than that of the Sham group, with significant difference (P0.05) and CA ES group CA. The level of CA in group 12h and ES after operation was significantly higher than that in group Sham (P0.05). 24h, CA levels in group ES increased significantly after operation (P0.05). (2) after operation, the level of lung tissue was significantly higher than that in CLP group (2) (3) the results of Western Blot showed that the expression of 6h, 12h, 24h, CLP, ES group TLR4, NF- kappa B protein increased significantly after the operation, and there was a significant difference in the expression of NF- kappa B protein. (4) the expression of kappa protein was significantly lower than that of the group. (4) after the operation Compared with the Sham group, there was a significant difference (P0.05), and the level of TNF- in ES group was significantly lower than that of the CLP group (P0.05). (5) the postoperative wet weight / dry weight of lung tissue in 6h, 12h, 24h, CLP, ES group, lung coefficient, lung water content, and alveolar lavage fluid protein levels were significantly higher than those of the Sham group. The level of tissue wet weight / dry weight, lung coefficient, lung water content and alveolar lavage fluid protein content were also significantly lower than that of the CLP group (P0.05). (6) the level of DAO in 6h, 12h, 24h, CLP, ES group decreased significantly after operation, and the difference was statistically significant compared with the Sham group (P0.05), and the DAO level in the ES group was also significantly higher than that in the group (P0.05). (7) 1 after the operation, 1 The i-FABP level of intestinal tissue in group 2h, 24h, CLP, ES was significantly lower than that of Sham group (P0.05), and the i-FABP level of ES group in each time point was also significantly higher than that of CLP group (P0.05). (8) pathological changes in lung tissue: the pathological damage degree of the Sham group was the lightest, the pathological damage of the group was the heaviest, and the pathological damage of each time point in each group was all Compared with group CLP, compared with group Sham, the pathological changes in the intestinal tissue: the pathological changes in the Sham group were the lightest, the pathological damage in the group CLP was the heaviest, and the pathological damage of the group ES was significantly reduced in the ES group than that in the CLP group. (10) esmolol could prolong the survival time of the sepsis rats. Conclusion the early body of sepsis was given. Excitement, releasing a large number of catecholamines, activating inflammatory factors, causing lung and intestinal damage. Esmolol can protect the lungs and intestines by promoting the secretion of catecholamine, inhibiting the release of inflammatory factors, reducing the permeability of the lungs and intestines, reducing the pulmonary edema and protecting the intestinal mucosal barrier. The mechanism may be esmolol To improve the responsiveness of beta receptor to catecholamine and to regulate the level of inflammatory factors by inhibiting the TLR4 - NF- kappa B - TNF- - alpha inflammatory signaling pathway, the protection of the lung is played by inhibiting the level of inflammatory factors to protect the intestinal tract.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R459.7
[Abstract]:Objective (1) to study the protective effect of short effect beta 1 receptor blocker, esmolol, on pulmonary injury in septic rats and explore its mechanism. (2) study the protective effect of short effect beta 1 receptor blocker, esmolol, on the intestinal injury of sepsis rats. Methods 72 SD male rats were randomly divided into sham operation group (group Sham), sepsis group (group CLP) and esmolol. Group (group ES). 6 rats were randomly selected to observe 7 days of survival. The remaining 18 rats were randomly divided into 6h, 12h and 24h subgroups, 6.Sham groups in each subgroup were treated with cecum, and both CLP and ES groups were established by cecal ligation and perforation (CLP). The left internal jugular vein was performed after the model was successfully established. Sham and CLP groups continued. The micropump was pumped into the physiological saline 1ml/h, a total of 6h, and the ES group was pumped into the esmolol diluent 1ml/h (15mg/kg/h). All the subgroups of 6h. were executed after 6h, 12h and 24h were executed after the model success. The CA of plasma, the level of TNF- alpha, the level of lung tissue and the level of the intestinal tissue were detected by ELISA method. TLR4, NF- kappa B protein expression level. Measurement of wet dry weight ratio of lung tissue, lung coefficient, water content, left lung alveolar lavage, the determination of the protein content in the lavage fluid. The lung and intestinal histopathological changes were observed under optical microscope. Results (1) the serum CA level in 6h, CLP, ES group after operation was significantly higher than that of the Sham group, with significant difference (P0.05) and CA ES group CA. The level of CA in group 12h and ES after operation was significantly higher than that in group Sham (P0.05). 24h, CA levels in group ES increased significantly after operation (P0.05). (2) after operation, the level of lung tissue was significantly higher than that in CLP group (2) (3) the results of Western Blot showed that the expression of 6h, 12h, 24h, CLP, ES group TLR4, NF- kappa B protein increased significantly after the operation, and there was a significant difference in the expression of NF- kappa B protein. (4) the expression of kappa protein was significantly lower than that of the group. (4) after the operation Compared with the Sham group, there was a significant difference (P0.05), and the level of TNF- in ES group was significantly lower than that of the CLP group (P0.05). (5) the postoperative wet weight / dry weight of lung tissue in 6h, 12h, 24h, CLP, ES group, lung coefficient, lung water content, and alveolar lavage fluid protein levels were significantly higher than those of the Sham group. The level of tissue wet weight / dry weight, lung coefficient, lung water content and alveolar lavage fluid protein content were also significantly lower than that of the CLP group (P0.05). (6) the level of DAO in 6h, 12h, 24h, CLP, ES group decreased significantly after operation, and the difference was statistically significant compared with the Sham group (P0.05), and the DAO level in the ES group was also significantly higher than that in the group (P0.05). (7) 1 after the operation, 1 The i-FABP level of intestinal tissue in group 2h, 24h, CLP, ES was significantly lower than that of Sham group (P0.05), and the i-FABP level of ES group in each time point was also significantly higher than that of CLP group (P0.05). (8) pathological changes in lung tissue: the pathological damage degree of the Sham group was the lightest, the pathological damage of the group was the heaviest, and the pathological damage of each time point in each group was all Compared with group CLP, compared with group Sham, the pathological changes in the intestinal tissue: the pathological changes in the Sham group were the lightest, the pathological damage in the group CLP was the heaviest, and the pathological damage of the group ES was significantly reduced in the ES group than that in the CLP group. (10) esmolol could prolong the survival time of the sepsis rats. Conclusion the early body of sepsis was given. Excitement, releasing a large number of catecholamines, activating inflammatory factors, causing lung and intestinal damage. Esmolol can protect the lungs and intestines by promoting the secretion of catecholamine, inhibiting the release of inflammatory factors, reducing the permeability of the lungs and intestines, reducing the pulmonary edema and protecting the intestinal mucosal barrier. The mechanism may be esmolol To improve the responsiveness of beta receptor to catecholamine and to regulate the level of inflammatory factors by inhibiting the TLR4 - NF- kappa B - TNF- - alpha inflammatory signaling pathway, the protection of the lung is played by inhibiting the level of inflammatory factors to protect the intestinal tract.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R459.7
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