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The Protective Effect of N-acetylcysteine (NAC) in Acute Lung Injury Induced by Hydrochloric Acid Aspiration in Rabbits

Author: LiuShuo
Tutor: WangChunTing
School: Zhengzhou University
Course: Anesthesiology
Keywords: N-acetylcysteine Aspiration Lung injury Nuclear factor-κB p38MAPK Glutathione Tumor necrosis factor-α Interleukin-6
CLC: R614
Type: Master's thesis
Year: 2002
Downloads: 51
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Abstract

Objective: Aspiration of gastric contents into the lung is a fatal complicationin clinical anesthesia, but there has not been an effective strategy to treat it yet. Therefore, prevention and cure of reflu and aspiration has always been a major research subject in the field of clinical anesthesia. The previous studies on the animal models established by aspirating hydrochloric acid(HCl), the main ingradients of gastric juice, revealed that the later phase induced by HC1 pathologically resembles acute respiratory distress syndrome (ARDS). The occurrence of ARDS is due to the unbalance of cytokines network, in which proinflammatory factors express excessively, thus activating a great number of polymorphonuclear neutrophils (PMN). It is these PMNs that aggregate in the inflammatory sites, release reactive oxygen species (ROS) and protease which result in lung tissue injury ultimately. Therefore, the cytokines and ROS are thought to play a pivotal role in the pathogenesis of HCl aspiration induced-lung injury. N-acetylcysteine(NAC) is an dftttbxidant, which can not only eliminate oxygen free radicals(OFR), but also can inhibit the actiyjtionfef Nuclear factor- KB (NF- K. B) and p38 Mitogen-activated protein kinase(MAPK). Recent studies revealed that NF- K B and pSSMAPK participated in the regulation of various proinflammatory factors, such as TNF- a , IL-6, IL-8, ICAM-1, so they were expected to become the main target in the treatment of acute lung injury. Although there has not been any report on NAC in the treatment of HC1 aspiration -induced lung injury, based on the previous research, it is reasonable to believe that NAC is an promising medicine to treat the disease attributed to its multi-aspects interference with the pathological process. By investigating the effect of NAC on PaCh, plasma IL-6, TNF- a and MDA, protein contents in BALF, GSH contents of lung tissue and so on, this study aim to observe the effects of NAC on the treatment of HCl aspiration-induced lung injury and explore its mechanisms tentatively, so as to provide theoretical bases for clinical application of this medicine to treate the complication.Method:Divided 30 of Japan long-ear rabbits into three groups randomly, with 10 in each group: A was injured group. After their tracheas had been cut open, the rabbits were instillated intratracheally with HCl (pH=1.5, 2ml/kg); B was treated group. After being administered with HCl in the same way as Group A, the rabbits were injected with NAC (150mg/kg) intravenously as treatment; C was controlled group. The same amount of Normal Saline was injected into the trachea, without applying any treatment. With continuous mechanical ventilation at 100% oxygen concentration, blood sample was taken in turn through the artery cannula before and Ih, 2h, 3h, 4h, 5h after the injury to measure PaO2, the contents of plasma IL-6, TNF- a , and MDA. Five hours later, the rabbits were killed. The right lungswere lavaged through the right main bronchus to obstain BALF, and then the number of leukocyte, the ratio of PMN to the total cells and the protein contents in BALF were calculated. The W/D ratio of the left upper lobe of lung is measured and then 0.5g tissue of the lower lobe was homogenated to measure the contents of GSH. The remaining parts were used to histopathologjc study. Results:1) Changes of PaO2: Ih after aspiration, PaCh in Group A and B decreased dramatically, thereafter, Group A remained at a low level to the end of the observation period; Group B began to restore 3h after the injury ( P<0.01), but failed to return to the baseline in the end (P<0.05).2) Changes of plasma MDA: Compared with the baseline, plasma MDA of Group A elevated dramatically Ih (P<0.01) and reached its summit 3h after the aspiration (P<0.01), thereafter remained at the high level until the end of the experiment. MDA of Group B was obviously inhibited by NAC and was significantly lower than that of Group A at different corresponding time points from 2h after the injury on (P<0.01). MDA of Group C di

The Protective Effect of N-acetylcysteine (NAC) in Acute Lung Injury Induced by Hydrochloric Acid Aspiration in Rabbits

Abstract

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