艾司洛爾對(duì)膿毒癥大鼠肺臟和腸道保護(hù)作用的實(shí)驗(yàn)研究
發(fā)布時(shí)間：2018-08-06 19:00
【摘要】：目的(1)研究短效β1受體阻滯劑艾司洛爾對(duì)膿毒癥大鼠肺損傷的保護(hù)作用,并探討其機(jī)制;(2)研究短效β1受體阻滯劑艾司洛爾對(duì)膿毒癥大鼠腸道損傷的保護(hù)作用。方法72只SD雄性大鼠,隨機(jī)分為假手術(shù)組(Sham組)、膿毒癥組(CLP組)和艾司洛爾組(ES組)。各組隨機(jī)抽取6只大鼠觀察7天生存情況,剩余18只大鼠又隨機(jī)分為6h、12h和24h三個(gè)亞組,每個(gè)亞組6只。Sham組采用盲腸探查術(shù),CLP和ES組均采用盲腸結(jié)扎穿孔(CLP)法建立膿毒癥模型。造模成功后均行左側(cè)頸內(nèi)靜脈置管,Sham和CLP組持續(xù)微量泵泵入生理鹽水1ml/h,共計(jì)6h;ES組持續(xù)泵入艾司洛爾稀釋液1ml/h(15mg/kg/h),共計(jì)6h。各亞組于造模成功后6h、12h及24h后處死大鼠采集標(biāo)本,采用ELISA法檢測(cè)血漿CA、TNF-α水平、肺組織NF-κB水平、腸道組織DAO、i-FABP水平。采用Western Blot法檢測(cè)肺組織TLR4、NF-κB蛋白表達(dá)水平。測(cè)量肺組織濕干重比率、肺系數(shù)、水含量,行左肺肺泡灌洗,測(cè)定灌洗液中蛋白含量。光學(xué)顯微鏡下觀察肺、腸道組織病理變化。結(jié)果(1)術(shù)后6h,CLP、ES組血清CA水平與Sham組相比明顯升高,具有顯著差異性(P0.05),且ES組CA水平比CLP組明顯升高(P0.05)。術(shù)后12h,ES組CA水平與Sham組相比仍明顯升高(P0.05);術(shù)后24h,ES組CA水平與CLP組相比明顯升高(P0.05)。(2)術(shù)后6h、12h、24h,CLP、ES組肺組織NF-κB水平明顯升高,與Sham組相比差異有統(tǒng)計(jì)學(xué)意義(P0.05),且各時(shí)間點(diǎn)ES組NF-κB水平也均比CLP組明顯降低(P0.05)。(3)Western Blot結(jié)果顯示,術(shù)后6h、12h、24h,CLP組、ES組TLR4、NF-κB蛋白表達(dá)明顯增高,與Sham組相比差異有統(tǒng)計(jì)學(xué)意義(P0.05),且各時(shí)間點(diǎn)ES組TLR4、NF-κB蛋白表達(dá)均比CLP組明顯降低(P0.05)。(4)術(shù)后6h、12h、24h,CLP、ES組血清TNF-ɑ水平與Sham組相比明顯升高,具有顯著差異性(P0.05),且各時(shí)間點(diǎn)ES組TNF-ɑ水平也均比CLP組明顯降低(P0.05)。(5)術(shù)后6h、12h、24h,CLP組、ES組肺組織濕重/干重、肺系數(shù)、肺水含量、肺泡灌洗液蛋白含量水平與Sham組相比均明顯升高(p0.05),且各時(shí)間點(diǎn)ES組肺組織濕重/干重、肺系數(shù)、肺水含量、肺泡灌洗液蛋白含量水平也均較CLP組明顯降低(p0.05)。(6)術(shù)后6h、12h、24h,CLP、ES組腸道組織DAO水平明顯降低,與Sham組相比差異有統(tǒng)計(jì)學(xué)意義(P0.05),且各時(shí)間點(diǎn)ES組DAO水平也均比CLP組明顯升高(P0.05)。(7)術(shù)后6h、12h、24h,CLP、ES組腸道組織i-FABP水平明顯降低,與Sham組相比差異有統(tǒng)計(jì)學(xué)意義(P0.05),且各時(shí)間點(diǎn)ES組i-FABP水平也均比CLP組明顯升高(P0.05)。(8)肺組織病理形態(tài)學(xué)改變:Sham組病理?yè)p傷程度最輕,CLP組病理?yè)p傷程度最重,ES組各時(shí)間點(diǎn)病理?yè)p傷均較CLP組明顯減輕,較Sham組明顯加重。(9)腸道組織病理形態(tài)學(xué)改變:Sham組病理?yè)p傷最輕,CLP組病理?yè)p傷程度最重,ES組各時(shí)間點(diǎn)病理?yè)p傷均較CLP組明顯減輕,較Sham組明顯加重。(10)艾司洛爾能延長(zhǎng)膿毒癥大鼠生存時(shí)間。結(jié)論膿毒癥早期機(jī)體交感神經(jīng)興奮,釋放大量?jī)翰璺影?激活炎癥因子,導(dǎo)致肺臟、腸道損傷。艾司洛爾通過(guò)促進(jìn)兒茶酚胺分泌,抑制炎癥因子釋放,降低肺臟及腸道的通透性,減輕肺水腫,保護(hù)腸粘膜屏障,進(jìn)而起到保護(hù)肺臟和腸道的作用。其機(jī)制可能為艾司洛爾改善β受體對(duì)兒茶酚胺的反應(yīng)性,通過(guò)抑制TLR4—NF-κB—TNF-α炎癥信號(hào)通路來(lái)調(diào)節(jié)炎癥因子水平,從而發(fā)揮對(duì)肺臟的保護(hù)作用。通過(guò)抑制炎癥因子水平,從而發(fā)揮對(duì)腸道的保護(hù)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.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：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.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R459.7
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