替米沙坦對(duì)大鼠機(jī)械通氣所致肺損傷保護(hù)作用的實(shí)驗(yàn)研究
發(fā)布時(shí)間：2019-05-03 19:01
【摘要】：目的：通過(guò)研究替米沙坦對(duì)機(jī)械通氣所致肺損傷(ventilator-induced lung injury,VILI)肺組織的病理改變和肺泡中炎性細(xì)胞因子水平的影響,探討替米沙坦對(duì)VILI的保護(hù)作用及可能的機(jī)制。 方法：采用大潮氣量-容量控制通氣(VCV)模式建立大鼠VILI動(dòng)物模型。40只成年健康雄性SD大鼠隨機(jī)均分為自主呼吸對(duì)照組(A組)、大潮氣量機(jī)械通氣組(B組)、機(jī)械通氣+小劑量(2.5mg/Kg)替米沙坦處理組(C組)、機(jī)械通氣+大劑量(5mg/kg)替米沙坦處理組(D組)。實(shí)驗(yàn)中4組大鼠均給予動(dòng)脈血?dú)夂脱鲃?dòng)力學(xué)監(jiān)測(cè), B、C、D組大鼠給予相同的通氣參數(shù)進(jìn)行容量控制通氣：潮氣量(Vt)為40ml/Kg；呼吸頻率為40次/分；吸氣/呼吸時(shí)間比值(I/E)為1：2；呼吸末正壓(PEEP)為0；吸入氣體為室內(nèi)空氣,實(shí)驗(yàn)時(shí)間為2小時(shí)。機(jī)械通氣前30min分別采用等量的替米沙坦(Telmisartan)溶液或PBS腹腔注射。實(shí)驗(yàn)至預(yù)定時(shí)間處死大鼠,光鏡下觀察肺病理改變并作Smith評(píng)分,免疫組織化學(xué)染色法檢測(cè)肺組織中AT1R和PPAR-γ蛋白的表達(dá),測(cè)定髓過(guò)氧化物酶(MPO)活性及肺濕干重比值(W/D),酶聯(lián)免疫吸附測(cè)定(ELISA)法測(cè)定支氣管肺泡灌洗液(BALF)中TNF-α及IL-8含量。 結(jié)果：未行機(jī)械通氣前,四組大鼠動(dòng)脈血PH值、平均動(dòng)脈壓(MAP)動(dòng)脈血二氧化碳分壓(PaCO2)及氧分壓(PO2)均無(wú)顯著性差異；實(shí)驗(yàn)中B、C、D組PH值呈升高趨勢(shì),MAP、PaCO2及PO：呈下降趨勢(shì)；通氣2小時(shí)后,與B組比較,C、D組MAP明顯降低(P0.05)；與A組比較,B、C、D組Smith評(píng)分、MPO活性、TNF-α和IL-8含量及W/D比值顯著升高(P0.05,P0.01),PPAR-γ蛋白表達(dá)顯著下降(P0.05,P0.01),AT1R蛋白表達(dá)顯著增加(P0.05,P0.01)；與B組比較,C、D組PPAR-γ蛋白表達(dá)顯著增加(P0.01),其余指標(biāo)明顯降低(P0.05,P0.01)；與C組比較,D組Smith評(píng)分、TNF-α及IL-8含量及AT1R蛋白表達(dá)顯著降低(P0.05),PPAR-γ蛋白表達(dá)顯著增加(P0.05)。 結(jié)論：預(yù)先應(yīng)用替米沙坦可顯著減輕機(jī)械通氣所致大鼠肺組織的損傷性改變。替米沙坦對(duì)VILI保護(hù)作用的機(jī)制可能是肺通過(guò)調(diào)節(jié)肺組織中PPAR-γ、 AT1R蛋白的表達(dá),抑制肺組織內(nèi)炎性細(xì)胞因子TNF-α與工L-8的合成與釋放,減少肺內(nèi)中性粒細(xì)胞的募集,從而減輕肺組織的損傷。
[Abstract]:Aim: to study the effect of telmisartan on the pathological changes of lung tissue and the level of inflammatory cytokines in alveolar tissue after mechanical ventilation-induced lung injury (ventilator-induced lung injury,VILI), and to explore the protective effect of telmisartan on VILI and its possible mechanism. Methods: 40 adult healthy male SD rats were randomly divided into control group (group A) and mechanical ventilation group (group B) with high tidal volume-volume controlled ventilation (VCV) model to establish VILI model of rats, and 40 healthy adult male SD rats were randomly divided into two groups: control group (group A) and mechanical ventilation group (group B). Low-dose mechanical ventilation (2.5mg/Kg) and telmisartan-treated group (group C) and high-dose mechanical ventilation (5mg/kg)-telmisartan-treated group (group D). Arterial blood gas and hemodynamics were monitored in all the four groups. Group B, C, D were given the same ventilation parameters for volume control ventilation: tidal volume (Vt) was 40 ml / kg, respiratory rate was 40 times / min (P < 0.01), and group B, C and D were given the same ventilation parameters for volume control ventilation. The inspiratory / respiratory time ratio (I / E) was 1-2; the positive end-breathing pressure (PEEP) was 0; the inhaled gas was indoor air and the experiment time was 2 hours. 30min was injected intraperitoneally with telmisartan (Telmisartan) solution or PBS before mechanical ventilation. The rats were killed at the scheduled time. The pathological changes and Smith score of lung were observed under light microscope. The expression of AT1R and PPAR- 緯 protein in lung tissue was detected by immunohistochemical staining. Myeloperoxidase (MPO) activity and lung wet-dry weight ratio (W / D) were measured. TNF- 偽 and IL-8 contents in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Results: before mechanical ventilation, there was no significant difference in arterial PH, mean arterial pressure (MAP), arterial partial pressure of carbon dioxide (PaCO2) and partial pressure of oxygen (PO2) among the four groups. After 2 hours of ventilation, MAP in group C and D was significantly lower than that in group B (P 0.05), but MAP,PaCO2 and PO: in group B, C, D were significantly lower than those in group B (P 0.05). Compared with group A, Smith score, MPO activity, content of TNF- 偽 and IL-8, and ratio of W / D were significantly increased in group B, C and D (P 0.05, P0.01), while expression of PPAR- 緯 protein was significantly decreased (P 0.05, P0.01), and that in group B, C, D was significantly higher than that in group A (P 0.05, P0.01). The expression of AT1R protein was significantly increased (P0.05, P0.01). Compared with group B, the expression of PPAR- 緯 protein in group C and D increased significantly (P0.01), while the other indexes decreased significantly (P0.05, P0.01). Compared with group C, Smith score, content of TNF- 偽 and IL-8 and expression of AT1R protein in group D were significantly lower than those in group C (P0.05), while expression of PPAR- 緯 protein was significantly increased (P0.05). Conclusion: telmisartan can relieve lung injury induced by mechanical ventilation in rats. The protective mechanism of telmisartan on VILI may be that lung reduces the recruitment of neutrophils by regulating the expression of PPAR- 緯 and AT1R proteins and inhibiting the synthesis and release of inflammatory cytokines TNF- 偽 and L-8 in lung tissue. In order to reduce the lung tissue damage.
【學(xué)位授予單位】：桂林醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R563.8
本文編號(hào)：2469188
[Abstract]:Aim: to study the effect of telmisartan on the pathological changes of lung tissue and the level of inflammatory cytokines in alveolar tissue after mechanical ventilation-induced lung injury (ventilator-induced lung injury,VILI), and to explore the protective effect of telmisartan on VILI and its possible mechanism. Methods: 40 adult healthy male SD rats were randomly divided into control group (group A) and mechanical ventilation group (group B) with high tidal volume-volume controlled ventilation (VCV) model to establish VILI model of rats, and 40 healthy adult male SD rats were randomly divided into two groups: control group (group A) and mechanical ventilation group (group B). Low-dose mechanical ventilation (2.5mg/Kg) and telmisartan-treated group (group C) and high-dose mechanical ventilation (5mg/kg)-telmisartan-treated group (group D). Arterial blood gas and hemodynamics were monitored in all the four groups. Group B, C, D were given the same ventilation parameters for volume control ventilation: tidal volume (Vt) was 40 ml / kg, respiratory rate was 40 times / min (P < 0.01), and group B, C and D were given the same ventilation parameters for volume control ventilation. The inspiratory / respiratory time ratio (I / E) was 1-2; the positive end-breathing pressure (PEEP) was 0; the inhaled gas was indoor air and the experiment time was 2 hours. 30min was injected intraperitoneally with telmisartan (Telmisartan) solution or PBS before mechanical ventilation. The rats were killed at the scheduled time. The pathological changes and Smith score of lung were observed under light microscope. The expression of AT1R and PPAR- 緯 protein in lung tissue was detected by immunohistochemical staining. Myeloperoxidase (MPO) activity and lung wet-dry weight ratio (W / D) were measured. TNF- 偽 and IL-8 contents in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Results: before mechanical ventilation, there was no significant difference in arterial PH, mean arterial pressure (MAP), arterial partial pressure of carbon dioxide (PaCO2) and partial pressure of oxygen (PO2) among the four groups. After 2 hours of ventilation, MAP in group C and D was significantly lower than that in group B (P 0.05), but MAP,PaCO2 and PO: in group B, C, D were significantly lower than those in group B (P 0.05). Compared with group A, Smith score, MPO activity, content of TNF- 偽 and IL-8, and ratio of W / D were significantly increased in group B, C and D (P 0.05, P0.01), while expression of PPAR- 緯 protein was significantly decreased (P 0.05, P0.01), and that in group B, C, D was significantly higher than that in group A (P 0.05, P0.01). The expression of AT1R protein was significantly increased (P0.05, P0.01). Compared with group B, the expression of PPAR- 緯 protein in group C and D increased significantly (P0.01), while the other indexes decreased significantly (P0.05, P0.01). Compared with group C, Smith score, content of TNF- 偽 and IL-8 and expression of AT1R protein in group D were significantly lower than those in group C (P0.05), while expression of PPAR- 緯 protein was significantly increased (P0.05). Conclusion: telmisartan can relieve lung injury induced by mechanical ventilation in rats. The protective mechanism of telmisartan on VILI may be that lung reduces the recruitment of neutrophils by regulating the expression of PPAR- 緯 and AT1R proteins and inhibiting the synthesis and release of inflammatory cytokines TNF- 偽 and L-8 in lung tissue. In order to reduce the lung tissue damage.
【學(xué)位授予單位】：桂林醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R563.8
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 王建春;姜鵬;黃建;錢桂生;;急性肺損傷大鼠肺組織PPAR-γ表達(dá)的研究[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2008年06期
2 馮丹;姚尚龍;尚游;武慶平;王立奎;;血管緊張素Ⅱ受體阻斷劑對(duì)大鼠機(jī)械通氣所致肺損傷的保護(hù)作用[J];中華急診醫(yī)學(xué)雜志;2007年09期
，本文編號(hào)：2469188
本文鏈接：http://sikaile.net/yixuelunwen/huxijib/2469188.html
最近更新
教材專著
