右美托咪定對大鼠急性肺損傷時肺組織NF-κB活性及細(xì)胞因子的影響
發(fā)布時間：2019-04-15 11:51
【摘要】：目的:觀察右美托咪定對大鼠急性肺損傷(ALI)時肺組織中NF-κB活性及細(xì)胞因子的影響。為臨床有效預(yù)防和治療ALI提供理論參考。方法:通過采用不同劑量右美托咪定(DEX)進(jìn)行預(yù)處理,觀察肺組織NF-κB的活化和表達(dá)、肺濕/干重(W/D)比值以及細(xì)胞因子含量的變化,探討Dex對ALI的肺保護(hù)作用及可能機(jī)制。健康SD大鼠72只,體重250~300g,隨機(jī)分為6組(n=12):對照組(C組);ALI組(A組);低、中、大劑量(0.5μg/kg、1.5μg/kg、4.5μg/kg)Dex組(D1、D2、D3組),NF-κB特異性抑制劑PDTC組(P組)。C組為假手術(shù)組,僅作動、靜脈穿刺,其余各組均行動、靜脈穿刺置管用于放血、回輸血液、監(jiān)測血壓和給藥,在10min內(nèi)股動脈放血至平均動脈壓(MAP)35~45mmHg,通過調(diào)節(jié)放血和回輸血液的速度和容量維持此MAP水平1h,建立ALI模型,然后回輸全部失血及等容生理鹽水。D1、D2、D3組于放血前30min分別靜脈注射Dex0.5μg/kg、1.5μg/kg、4.5μg/kg。P組于放血前30min腹腔注射PDTC200mg/kg。建模后6小時處死大鼠取肺組織、支氣管肺泡灌洗液(BALF),HE染色觀察病理改變情況,稱重測量肺組織濕/干重(W/D)比值,酶聯(lián)免疫吸附法(ELISA)檢測支氣管肺泡灌洗液中的IL-6、il-10和tnf-α濃度,采用免疫組化(sabc)法觀察肺組織nf-κb的表達(dá)。結(jié)果:①病理學(xué)觀察:c組大鼠肺組織鏡下結(jié)構(gòu)完整,肺間質(zhì)無水腫,無炎性細(xì)胞侵潤;a組大鼠肺組織結(jié)構(gòu)破壞嚴(yán)重,肺間質(zhì)水腫明顯,可見大量炎性細(xì)胞侵潤,肺泡內(nèi)可見大量漏出紅細(xì)胞;d1組、d2組和d3組大鼠肺組織結(jié)構(gòu)破壞程度、肺間質(zhì)水腫、炎性細(xì)胞侵潤方面較a組有不同程度減輕,且隨著右美托咪定劑量的增加肺損傷減輕越明顯;p組肺損傷程度較a組有顯著減輕,與d3組無明顯差異。②肺組織nf-κb表達(dá):c組大鼠肺組織中可見少量nf-κb陽性細(xì)胞;a組大鼠肺組織中nf-κb陽性細(xì)胞較c組明顯增多(p0.01);d1組大鼠肺組織中nf-κb陽性細(xì)胞與a組無明顯差異(p0.05);d2組和d3組大鼠肺組織中nf-κb陽性細(xì)胞較a組顯著減少(p0.01),且隨著右美托咪定劑量的增大nf-κb陽性細(xì)胞減少越明顯;p組大鼠肺組織中nf-κb陽性細(xì)胞均少于d1組、d2組和d3組(p0.01或p0.05)。③支氣管肺泡灌洗液中細(xì)胞因子含量:與c組比較,a組il-6、il-10和tnf-α含量明顯升高(p0.01);與a組比較,d1組il-6、il-10和tnf-α含量降低不明顯(p0.05),但d2組和d3組均顯著下降(p0.01),且隨著右美托咪定劑量的增大下降幅度越大;與p組比較,d1組il-6、il-10和tnf-α含量明顯升高(p0.01),d2組il-6含量無明顯差異(p0.05),但il-10和tnf-α含量顯著升高(p0.01)。④肺組織w/d比值:與c組比較,a組和d1組肺組織w/d比值明顯升高(p0.01);與a組比較,d2組、d3組和p組肺組織w/d比值均明顯降低(p0.01);與p組比較,D1組肺組織W/D比值明顯升高(p0.01)。結(jié)論:①右美托咪定預(yù)處理對大鼠急性肺損傷有一定保護(hù)作用;②右美托咪定的肺保護(hù)作用可能與其抑制NF-κB活化以及炎性細(xì)胞因子的生成有關(guān)。
[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- 偽 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- 偽 were significantly increased (p0.01). Compared with group a, the contents of il-6,il-10 and tnf- 偽 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- 偽 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- 偽 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.
【學(xué)位授予單位】：四川醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R614
本文編號：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- 偽 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- 偽 were significantly increased (p0.01). Compared with group a, the contents of il-6,il-10 and tnf- 偽 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- 偽 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- 偽 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.
【學(xué)位授予單位】：四川醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R614
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 郭偉;王奇;陳云波;;細(xì)胞核因子κB信號轉(zhuǎn)導(dǎo)途徑內(nèi)的活化與調(diào)節(jié)機(jī)制研究進(jìn)展[J];實(shí)用醫(yī)學(xué)雜志;2006年11期
2 ;急性肺損傷/急性呼吸窘迫綜合征診斷與治療指南(2006)[J];中華內(nèi)科雜志;2007年05期
，本文編號：2458122
本文鏈接：http://sikaile.net/yixuelunwen/waikelunwen/2458122.html
最近更新
教材專著
