右美托咪定对大鼠急性肺损伤时肺组织NF-κB活性及细胞因子的影响
发布时间：2019-04-15 11:51
【摘要】：目的:观察右美托咪定对大鼠急性肺损伤(ALI)时肺组织中NF-κB活性及细胞因子的影响。为临床有效预防和治疗ALI提供理论参考。方法:通过采用不同剂量右美托咪定(DEX)进行预处理,观察肺组织NF-κB的活化和表达、肺湿/干重(W/D)比值以及细胞因子含量的变化,探讨Dex对ALI的肺保护作用及可能机制。健康SD大鼠72只,体重250~300g,随机分为6组(n=12):对照组(C组);ALI组(A组);低、中、大剂量(0.5μg/kg、1.5μg/kg、4.5μg/kg)Dex组(D1、D2、D3组),NF-κB特异性抑制剂PDTC组(P组)。C组为假手术组,仅作动、静脉穿刺,其余各组均行动、静脉穿刺置管用于放血、回输血液、监测血压和给药,在10min内股动脉放血至平均动脉压(MAP)35~45mmHg,通过调节放血和回输血液的速度和容量维持此MAP水平1h,建立ALI模型,然后回输全部失血及等容生理盐水。D1、D2、D3组于放血前30min分别静脉注射Dex0.5μg/kg、1.5μg/kg、4.5μg/kg。P组于放血前30min腹腔注射PDTC200mg/kg。建模后6小时处死大鼠取肺组织、支气管肺泡灌洗液(BALF),HE染色观察病理改变情况,称重测量肺组织湿/干重(W/D)比值,酶联免疫吸附法(ELISA)检测支气管肺泡灌洗液中的IL-6、il-10和tnf-α浓度,采用免疫组化(sabc)法观察肺组织nf-κb的表达。结果:①病理学观察:c组大鼠肺组织镜下结构完整,肺间质无水肿,无炎性细胞侵润;a组大鼠肺组织结构破坏严重,肺间质水肿明显,可见大量炎性细胞侵润,肺泡内可见大量漏出红细胞;d1组、d2组和d3组大鼠肺组织结构破坏程度、肺间质水肿、炎性细胞侵润方面较a组有不同程度减轻,且随着右美托咪定剂量的增加肺损伤减轻越明显;p组肺损伤程度较a组有显著减轻,与d3组无明显差异。②肺组织nf-κb表达:c组大鼠肺组织中可见少量nf-κb阳性细胞;a组大鼠肺组织中nf-κb阳性细胞较c组明显增多(p0.01);d1组大鼠肺组织中nf-κb阳性细胞与a组无明显差异(p0.05);d2组和d3组大鼠肺组织中nf-κb阳性细胞较a组显著减少(p0.01),且随着右美托咪定剂量的增大nf-κb阳性细胞减少越明显;p组大鼠肺组织中nf-κb阳性细胞均少于d1组、d2组和d3组(p0.01或p0.05)。③支气管肺泡灌洗液中细胞因子含量:与c组比较,a组il-6、il-10和tnf-α含量明显升高(p0.01);与a组比较,d1组il-6、il-10和tnf-α含量降低不明显(p0.05),但d2组和d3组均显著下降(p0.01),且随着右美托咪定剂量的增大下降幅度越大;与p组比较,d1组il-6、il-10和tnf-α含量明显升高(p0.01),d2组il-6含量无明显差异(p0.05),但il-10和tnf-α含量显著升高(p0.01)。④肺组织w/d比值:与c组比较,a组和d1组肺组织w/d比值明显升高(p0.01);与a组比较,d2组、d3组和p组肺组织w/d比值均明显降低(p0.01);与p组比较,D1组肺组织W/D比值明显升高(p0.01)。结论:①右美托咪定预处理对大鼠急性肺损伤有一定保护作用;②右美托咪定的肺保护作用可能与其抑制NF-κB活化以及炎性细胞因子的生成有关。
[Abstract]:Aim: to observe the effect of right metomide on the activity of NF- kappa B and cytokines in lung tissue of rats with acute lung injury (ALI). To provide a theoretical reference for the clinical effective prevention and treatment of ALI. Methods: the activation and expression of NF- 魏 B, the ratio of wet / dry weight (W / D) and the content of cytokines in lung tissue were observed by pretreatment with different doses of right metametrimidine (DEX). To investigate the pulmonary protective effect of Dex on ALI and its possible mechanism. 72 healthy SD rats, weighing 250 to 300 g, were randomly divided into 6 groups (n = 12): control group (group C,); ALI, group A); Low, middle, high dose (0.5 渭 g / kg, 1.5 渭 g / kg, 4.5 渭 g / kg) Dex group), NF- kappa B specific inhibitor PDTC group (P group). C group: sham-operated group, operation only, venipuncture, D _ 1, D _ 2, D _ 3 group). The other groups were treated with intravenous catheterization for bleeding, blood transfusion, blood pressure monitoring and drug administration. The internal femoral artery in 10min was released to the mean arterial pressure of (MAP) 35 to 45 mm Hg, and the MAP level was maintained for 1 hour by regulating the speed and volume of bleeding and blood transfusion. The model of ALI was established, and then all blood loss and isocapillary saline were injected intraperitoneally in group D _ 1, D _ 2, D _ 3 before 30min was injected intravenously with PDTC200mg/kg. (0.5 渭 g / kg, 1.5 渭 g / kg, 4.5 渭 g / kg.P) before bleeding in group D _ 1 and D _ 2, group D _ 3 were injected intraperitoneally with PDTC200mg/kg. before bleeding. The lung tissue was taken from the rats at 6 hours after modeling, the pathological changes were observed by (BALF), HE staining in bronchoalveolar lavage fluid, and the wet / dry weight (W / D) ratio of lung tissue was measured. The concentration of IL-6,il-10 and tnf- 伪 in bronchoalveolar lavage fluid was measured by enzyme linked immunosorbent assay (ELISA), and the expression of nf- kappa b in lung tissue was detected by immunohistochemical (sabc) method. Results: (1) pathological observation: in group C, the structure of lung tissue was intact under microscope, and there was no edema in lung interstitial matter and no inflammatory cell invasion in group C; In group a, the lung tissue structure was destroyed seriously, pulmonary interstitial edema was obvious, a large number of inflammatory cells were infiltrated and a large number of red blood cells were leaking out of the alveoli. The degree of lung tissue structure damage, pulmonary interstitial edema and inflammatory cell invasion in D1, D2 and d3 groups were significantly lower than those in group a, and the lung injury was alleviated more obviously with the increase of right metametomidine dose as well as the degree of pulmonary interstitial edema and inflammatory cell invasion in d1, d2 and d3 groups were significantly lower than that in group a. (2) the expression of nf- 魏 b in lung tissue: in group C, a few nf- 魏 b positive cells were found in lung tissue of group C, and there was no significant difference in the degree of lung injury between group a and group a, and there was no significant difference in expression of nf- 魏 b between group P and group a. The number of nf- 魏 b positive cells in lung tissue in group a was significantly higher than that in group c (p0.01), but there was no significant difference in nf- 魏 b positive cells between group a and group a (p0.05). The number of nf- 魏 b positive cells in lung tissue of d2 and d3 groups was significantly lower than that of a group (p0.01), and the decrease of nf- 魏 b positive cells was more obvious with the increase of right metametramine dose. The number of nf- 魏 b positive cells in lung tissue of group P was lower than that of group 1, group 2 and group 3 (p0.01 or p0.05). Cytokine content in bronchoalveolar lavage fluid of 3 groups: compared with group c, il-6, in group a was significantly lower than that in group C (p0.01 or p0.05). The contents of il-10 and tnf- 伪 were significantly increased (p0.01). Compared with group a, the contents of il-6,il-10 and tnf- 伪 in day 1 group did not decrease significantly (p0.05), but those in day 2 and day 3 groups decreased significantly (p0.01), and the decrease increased with the increase of the dose of right metametramine. Compared with p group, the contents of il-6,il-10 and tnf- 伪 in day 1 group were significantly higher than those in p group (p0.01), but there was no significant difference in il-6 content between day 2 group and control group (p0.05). However, the contents of il-10 and tnf- 伪 were significantly increased (p0.01). (4) the w / d ratio of lung tissue was significantly higher in group a and d 1 than that in group c (p0.01), and that in group a and d 1 was significantly higher than that in group C (p0.01). Compared with group a, the w / d ratio of lung tissue in group D 2, group 3 and group p was significantly lower than that in group a (p0.01), and the ratio of W / D in group D 1 was significantly higher than that in group P (p 0.01). Conclusion: 1 the pretreatment with right metometrimidine has a protective effect on acute lung injury in rats, and the pulmonary protective effect of right metomidine may be related to its inhibition of the activation of NF- 魏 B and the production of inflammatory cytokines.
【学位授予单位】：四川医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R614
本文编号：2458122
[Abstract]:Aim: to observe the effect of right metomide on the activity of NF- kappa B and cytokines in lung tissue of rats with acute lung injury (ALI). To provide a theoretical reference for the clinical effective prevention and treatment of ALI. Methods: the activation and expression of NF- 魏 B, the ratio of wet / dry weight (W / D) and the content of cytokines in lung tissue were observed by pretreatment with different doses of right metametrimidine (DEX). To investigate the pulmonary protective effect of Dex on ALI and its possible mechanism. 72 healthy SD rats, weighing 250 to 300 g, were randomly divided into 6 groups (n = 12): control group (group C,); ALI, group A); Low, middle, high dose (0.5 渭 g / kg, 1.5 渭 g / kg, 4.5 渭 g / kg) Dex group), NF- kappa B specific inhibitor PDTC group (P group). C group: sham-operated group, operation only, venipuncture, D _ 1, D _ 2, D _ 3 group). The other groups were treated with intravenous catheterization for bleeding, blood transfusion, blood pressure monitoring and drug administration. The internal femoral artery in 10min was released to the mean arterial pressure of (MAP) 35 to 45 mm Hg, and the MAP level was maintained for 1 hour by regulating the speed and volume of bleeding and blood transfusion. The model of ALI was established, and then all blood loss and isocapillary saline were injected intraperitoneally in group D _ 1, D _ 2, D _ 3 before 30min was injected intravenously with PDTC200mg/kg. (0.5 渭 g / kg, 1.5 渭 g / kg, 4.5 渭 g / kg.P) before bleeding in group D _ 1 and D _ 2, group D _ 3 were injected intraperitoneally with PDTC200mg/kg. before bleeding. The lung tissue was taken from the rats at 6 hours after modeling, the pathological changes were observed by (BALF), HE staining in bronchoalveolar lavage fluid, and the wet / dry weight (W / D) ratio of lung tissue was measured. The concentration of IL-6,il-10 and tnf- 伪 in bronchoalveolar lavage fluid was measured by enzyme linked immunosorbent assay (ELISA), and the expression of nf- kappa b in lung tissue was detected by immunohistochemical (sabc) method. Results: (1) pathological observation: in group C, the structure of lung tissue was intact under microscope, and there was no edema in lung interstitial matter and no inflammatory cell invasion in group C; In group a, the lung tissue structure was destroyed seriously, pulmonary interstitial edema was obvious, a large number of inflammatory cells were infiltrated and a large number of red blood cells were leaking out of the alveoli. The degree of lung tissue structure damage, pulmonary interstitial edema and inflammatory cell invasion in D1, D2 and d3 groups were significantly lower than those in group a, and the lung injury was alleviated more obviously with the increase of right metametomidine dose as well as the degree of pulmonary interstitial edema and inflammatory cell invasion in d1, d2 and d3 groups were significantly lower than that in group a. (2) the expression of nf- 魏 b in lung tissue: in group C, a few nf- 魏 b positive cells were found in lung tissue of group C, and there was no significant difference in the degree of lung injury between group a and group a, and there was no significant difference in expression of nf- 魏 b between group P and group a. The number of nf- 魏 b positive cells in lung tissue in group a was significantly higher than that in group c (p0.01), but there was no significant difference in nf- 魏 b positive cells between group a and group a (p0.05). The number of nf- 魏 b positive cells in lung tissue of d2 and d3 groups was significantly lower than that of a group (p0.01), and the decrease of nf- 魏 b positive cells was more obvious with the increase of right metametramine dose. The number of nf- 魏 b positive cells in lung tissue of group P was lower than that of group 1, group 2 and group 3 (p0.01 or p0.05). Cytokine content in bronchoalveolar lavage fluid of 3 groups: compared with group c, il-6, in group a was significantly lower than that in group C (p0.01 or p0.05). The contents of il-10 and tnf- 伪 were significantly increased (p0.01). Compared with group a, the contents of il-6,il-10 and tnf- 伪 in day 1 group did not decrease significantly (p0.05), but those in day 2 and day 3 groups decreased significantly (p0.01), and the decrease increased with the increase of the dose of right metametramine. Compared with p group, the contents of il-6,il-10 and tnf- 伪 in day 1 group were significantly higher than those in p group (p0.01), but there was no significant difference in il-6 content between day 2 group and control group (p0.05). However, the contents of il-10 and tnf- 伪 were significantly increased (p0.01). (4) the w / d ratio of lung tissue was significantly higher in group a and d 1 than that in group c (p0.01), and that in group a and d 1 was significantly higher than that in group C (p0.01). Compared with group a, the w / d ratio of lung tissue in group D 2, group 3 and group p was significantly lower than that in group a (p0.01), and the ratio of W / D in group D 1 was significantly higher than that in group P (p 0.01). Conclusion: 1 the pretreatment with right metometrimidine has a protective effect on acute lung injury in rats, and the pulmonary protective effect of right metomidine may be related to its inhibition of the activation of NF- 魏 B and the production of inflammatory cytokines.
【学位授予单位】：四川医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R614
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相关期刊论文 前2条
1 郭伟;王奇;陈云波;;细胞核因子κB信号转导途径内的活化与调节机制研究进展[J];实用医学杂志;2006年11期
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