噻托溴銨對煙霧吸入性損傷大鼠肺的保護作用
發(fā)布時間：2018-11-18 13:11
【摘要】：目的吸入性損傷是燒傷患者的頭號殺手,具有很高的發(fā)生率和死亡率。它會導(dǎo)致氣道梗阻、肺不張或肺萎陷,最終造成呼吸功能衰竭。噻托溴銨屬于高選擇性M1,M3受體長效拮抗藥,目前廣泛應(yīng)用于COPD和哮喘穩(wěn)定期治療,用以擴張支氣管,減少粘液分泌。它還對COPD氣道炎癥和重塑具有抑制作用。本實驗以煙霧吸入性損傷大鼠為模型,通過研究霧化吸入噻托溴銨后大鼠肺組織的病理變化、炎癥反應(yīng)以及氧化反應(yīng)的變化,來探討噻托溴銨對煙霧吸入性損傷后肺的保護作用。 方法將42只健康雄性SD大鼠隨機分成3組：假傷組(n=10,未損傷),治療組(n=16,傷后予噻托溴銨治療),對照組(n=16,損傷未予噻托溴銨治療),假傷組未予處理,對照組和治療組建立煙霧吸入性損傷模型,傷后1小時開始,治療組吸入噻托溴銨36微克(μg)/3ml生理鹽水,對照組吸入3m1生理鹽水,20分鐘吸完,每8小時重復(fù)給藥一次。于傷后24小時處死大鼠,腹主動脈取血,離心后測血清白介素(IL)-6、IL-10、腫瘤壞死因子(TNF)-α；剖胸取左肺,用10%甲醛固定,切片、染色后用光鏡進行病理形態(tài)學(xué)觀察；取右肺組織,用離心機制成勻漿,取上清液測髓過氧化物酶(MPO)、丙二醛(MDA)和超氧化物歧化酶(SOD)。對所得數(shù)據(jù)使用SPSS13.0統(tǒng)計軟件進行處理,各組均數(shù)采用單因素ANOVA進行分析。 結(jié)果1.一般情況觀察：致傷后大鼠出現(xiàn)精神萎靡,呼吸、心率加快的癥狀,將大鼠放在空曠區(qū)休息10分鐘,上述癥狀逐漸改善。 2.肺組織大體及光學(xué)顯微鏡觀察：假傷組大鼠肺組織呈粉紅色,無充血、水腫及出血。對照組可見充血、水腫,散在斑點狀出血,治療組充血、水腫及出血較對照組減輕。H.E染色顯示,假傷組肺泡腔清晰,結(jié)構(gòu)完整,肺泡壁光滑,間隔均勻一致,肺泡腔中無滲液及炎性細胞。損傷后肺組織明顯水腫、滲出及出血,肺泡組織破壞,出現(xiàn)局灶性肺不張及肺萎陷,肺泡壁明顯增厚,肺泡腔內(nèi)可見粘液分泌及炎細胞滲出。噻托溴銨治療組肺組織充血、水腫及出血有所減輕,肺泡壁稍有增厚,肺泡腔內(nèi)粘液分泌及炎細胞滲出減少。 3.各組大鼠血清TNF-α,IL-6及IL-10的比較：對照組和治療組血清TNF-α、IL-6、IL-10均高于假傷組(P0.01)。治療組IL-6、TNF-α低于對照組(P0.01)IL-10高于對照組(P0.01)。 4.各組大鼠肺組織MPO、MDA、SOD的比較：對照組和治療組肺勻漿MPO、MDA水平高于假傷組(P0.01),SOD水平低于假傷組(P0.01)。治療組MDA、MPO均低于對照組(P0.01),SOD高于對照組(P0.01)。 結(jié)論噻托溴銨可以減輕支氣管梗阻,降低肺不張和(或)肺萎陷的發(fā)生率；可以抑制促炎因子IL-6、TNF-α的釋放,促進抗炎因子IL-10的釋放,減輕過度炎癥反應(yīng)對機體的損傷；還可以降低損傷后肺組織MPO, MDA水平,提高SOD活性,具有抗氧化的作用。因此,噻托溴銨對煙霧吸入性損傷大鼠肺具有保護作用。
[Abstract]:Objective inhalation injury is the leading killer of burn patients with high incidence and mortality. It can lead to obstruction of the airway, atelectasis or collapse of the lung, leading to respiratory failure. Tiotropium bromide is a long-acting antagonist of highly selective M _ (1) N _ (3) receptor. It is widely used in the treatment of COPD and asthma stable period to dilate bronchi and reduce mucus secretion. It also inhibits airway inflammation and remodeling in COPD. In this study, the pathological changes of lung tissue, the inflammatory reaction and the oxidative reaction of the rats after inhalation of tiotropium bromide were studied by using smoke inhalation injury as the model. To investigate the protective effect of tiotropium bromide on lung after smoke inhalation injury. Methods Forty-two healthy male SD rats were randomly divided into three groups: sham injury group (n = 10, no injury), treatment group (n = 16, treated with tiotropium bromide after injury), control group (n = 16, injury was not treated with tiotropium bromide), and sham injury group, without treatment. Smoke inhalation injury model was established in the control group and the treatment group. Starting from 1 hour after injury, the treatment group inhaled 36 渭 g (渭 g) / 3ml normal saline of tiotropium bromide, while the control group inhaled 3m1 saline for 20 minutes, and repeated administration every 8 hours. The rats were sacrificed 24 hours after injury, blood was taken from abdominal aorta, serum interleukin (IL)-6 and tumor necrosis factor (TNF)-偽 were measured after centrifugation. The left lung was dissected and fixed with 10% formaldehyde. The right lung tissue was taken and made into homogenate by centrifuge. The supernatant was used to measure (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD).) in supernatant. The data were processed by SPSS13.0 software, and the mean of each group was analyzed by single factor ANOVA. Result 1. General observation: after injury, the rats developed symptoms of mental retardation, respiration, and accelerated heart rate. The rats were placed in an open area for 10 minutes to rest, and the above symptoms gradually improved. 2. Gross and optical microscope observation of lung tissue: the pulmonary tissue of sham injury group was pink, without hyperemia, edema and haemorrhage. Hyperemia, edema and speckle hemorrhage were observed in the control group. The congestion, edema and bleeding in the treatment group were less than those in the control group. The alveolar cavity was clear, the structure was intact, the alveolar wall was smooth and the interval was uniform in the sham injury group. No exudate or inflammatory cells were found in the alveolar cavity. After injury, there were obvious edema, exudation and hemorrhage of lung tissue, destruction of alveolar tissue, focal atelectasis and collapse of lung, obvious thickening of alveolar wall, mucus secretion and inflammatory cell exudation in alveolar cavity. The hyperemia, edema and hemorrhage of lung tissue were alleviated, alveolar wall was slightly thickened, mucus secretion and inflammatory cell exudation were decreased in tiotropium treatment group. 3. Comparison of serum TNF- 偽, IL-6 and IL-10: serum TNF- 偽 and IL-6,IL-10 in control group and treatment group were higher than those in sham injury group (P0.01). The IL-6,TNF- 偽 in the treatment group was lower than that in the control group (P 0.01) and the IL-10 was higher in the treatment group than in the control group (P 0.01). 4. Comparison of MPO,MDA,SOD in lung tissue of rats in each group: the level of MPO,MDA in lung homogenate of control group and treatment group was higher than that of sham injury group (P0.01), SOD level was lower than that of sham injury group (P0.01). The MDA,MPO of the treatment group was lower than that of the control group (P0.01), SOD was higher than that of the control group (P0.01). Conclusion Tiotropium bromide can relieve bronchial obstruction and reduce the incidence of atelectasis and / or pulmonary collapse. It can inhibit the release of pro-inflammatory factor IL-6,TNF- 偽, promote the release of anti-inflammatory factor IL-10, and alleviate the damage caused by excessive inflammatory reaction. It can also reduce the level of MPO, MDA and increase the activity of SOD after injury. Therefore, tiotropium bromide has protective effect on lung injury induced by smoke inhalation in rats.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R644
本文編號：2340121
[Abstract]:Objective inhalation injury is the leading killer of burn patients with high incidence and mortality. It can lead to obstruction of the airway, atelectasis or collapse of the lung, leading to respiratory failure. Tiotropium bromide is a long-acting antagonist of highly selective M _ (1) N _ (3) receptor. It is widely used in the treatment of COPD and asthma stable period to dilate bronchi and reduce mucus secretion. It also inhibits airway inflammation and remodeling in COPD. In this study, the pathological changes of lung tissue, the inflammatory reaction and the oxidative reaction of the rats after inhalation of tiotropium bromide were studied by using smoke inhalation injury as the model. To investigate the protective effect of tiotropium bromide on lung after smoke inhalation injury. Methods Forty-two healthy male SD rats were randomly divided into three groups: sham injury group (n = 10, no injury), treatment group (n = 16, treated with tiotropium bromide after injury), control group (n = 16, injury was not treated with tiotropium bromide), and sham injury group, without treatment. Smoke inhalation injury model was established in the control group and the treatment group. Starting from 1 hour after injury, the treatment group inhaled 36 渭 g (渭 g) / 3ml normal saline of tiotropium bromide, while the control group inhaled 3m1 saline for 20 minutes, and repeated administration every 8 hours. The rats were sacrificed 24 hours after injury, blood was taken from abdominal aorta, serum interleukin (IL)-6 and tumor necrosis factor (TNF)-偽 were measured after centrifugation. The left lung was dissected and fixed with 10% formaldehyde. The right lung tissue was taken and made into homogenate by centrifuge. The supernatant was used to measure (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD).) in supernatant. The data were processed by SPSS13.0 software, and the mean of each group was analyzed by single factor ANOVA. Result 1. General observation: after injury, the rats developed symptoms of mental retardation, respiration, and accelerated heart rate. The rats were placed in an open area for 10 minutes to rest, and the above symptoms gradually improved. 2. Gross and optical microscope observation of lung tissue: the pulmonary tissue of sham injury group was pink, without hyperemia, edema and haemorrhage. Hyperemia, edema and speckle hemorrhage were observed in the control group. The congestion, edema and bleeding in the treatment group were less than those in the control group. The alveolar cavity was clear, the structure was intact, the alveolar wall was smooth and the interval was uniform in the sham injury group. No exudate or inflammatory cells were found in the alveolar cavity. After injury, there were obvious edema, exudation and hemorrhage of lung tissue, destruction of alveolar tissue, focal atelectasis and collapse of lung, obvious thickening of alveolar wall, mucus secretion and inflammatory cell exudation in alveolar cavity. The hyperemia, edema and hemorrhage of lung tissue were alleviated, alveolar wall was slightly thickened, mucus secretion and inflammatory cell exudation were decreased in tiotropium treatment group. 3. Comparison of serum TNF- 偽, IL-6 and IL-10: serum TNF- 偽 and IL-6,IL-10 in control group and treatment group were higher than those in sham injury group (P0.01). The IL-6,TNF- 偽 in the treatment group was lower than that in the control group (P 0.01) and the IL-10 was higher in the treatment group than in the control group (P 0.01). 4. Comparison of MPO,MDA,SOD in lung tissue of rats in each group: the level of MPO,MDA in lung homogenate of control group and treatment group was higher than that of sham injury group (P0.01), SOD level was lower than that of sham injury group (P0.01). The MDA,MPO of the treatment group was lower than that of the control group (P0.01), SOD was higher than that of the control group (P0.01). Conclusion Tiotropium bromide can relieve bronchial obstruction and reduce the incidence of atelectasis and / or pulmonary collapse. It can inhibit the release of pro-inflammatory factor IL-6,TNF- 偽, promote the release of anti-inflammatory factor IL-10, and alleviate the damage caused by excessive inflammatory reaction. It can also reduce the level of MPO, MDA and increase the activity of SOD after injury. Therefore, tiotropium bromide has protective effect on lung injury induced by smoke inhalation in rats.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R644
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