Protective Effection And Mechanism Of Dexmedetomidine On Acute Lung Injury In Rats

OBJECTIVE:To observe protective effect of Dexmedetomidine on acute lung injury in rats and explore its possible mechanisms.METHODS:Rats were randomly divided into 6 groups:normal control group(NS group,0.5 ml), LPS model group(LPS group,4 mg/kg), high-,meddle-, low-does Dex group (4.5μg/kg,1.5 u g/kg,0.5μg/kg)and YHB antergic group (YHB group,0.1 mg/kg), which 8 in each group. After an intraperitoneal injection of pentobarbital sodium (30 mg/kg), the rats were performed tracheostomy and reserved spontaneously breathing. The right femoral veins were incise and placed a cannula to administer drug. Each Dex groups were given intravenous Dex followed preceding does(4.5 u g/kg,1.5μg/kg,0.5 u g/kg). Except for NS group, other groups were all administered 4 mg/kg LPS which were dissolved into 0.5 ml NS. YHB group were injected Yohimbine 0.1 mg/kg additionally. The rats were killed after 6 hour. Their lungs were separated and weighed to calculate organ/body coefficients of lung tissue, photographed the appearance. The low right lungs were separated, recorded the wet weight, then placed in a drying baker. After 72 hour, the lung were taken out and recorded the dry weight to determine the wet/dry ratios. The right middle lungs were disassociated to make the 10% homogenate with NS,then collected the clear supernatant liquid. The concentration of TNF-a, IL-1βand IL-6 inflammatory factor were measured by Elisa. The right upper were segregated and placed in the 10% formalin in 24 hour. Then the lungs were embedded in paraffin, cutted, stained with haematoxylin-eosin(HE) for histological observation by light microscopy, meanwhile, detected the expression of NF-κB by immunohisto-chemisty. The left lungs were separated to measured expression of the TLR4 mRNA by RT-PCR.RESULTS:(1) Observing each group's lung tissues, the appearance in NS group was smooth, pink, flexible,no edema and infarction;Lung in LPS group was crimson, in-flexible, found lots of hyperemia and bleeding point. Each Dex group'lung was red, had hyperemia and bleeding point, but not much as LPS group. We could found that the degree of ALI was alleviative with increasing does in Dex.(2)Compared with rats in NS group, the organ/body coefficients and wet/dry ratios in LPS group were evidently increased(P＜0.01); Compared with LPS group, the organ/body coefficients and wet/dry ratios in high-, middle-does Dex group were evidently decreased (P＜0.05 or P＜0.01).(3)Compared with rats in NS group, the concentration of TNF-a,IL-1βand IL-6 inflammatory factor in LPS group were obviously increased(P＜0.01); Compared with LPS group, the concentration of TNF-α, IL-1βand IL-6 inflammatory factor in high-, middle-does Dex group were obviously decreased (p＜0.05 or P＜0.01). The concentration of IL-1βand IL-6 inflammatory factor in YHB group were obviously decreased (p＜0.01) except for TNF-α.Compared with rats in YHB group, the concentration of inflammatory factor in high-and middle-does were obviously decreased (p＜0.01).(4) Under light microscope, the histological damage occurred in LPS group characterized by alveolar haemorrhage, interstitial oedema, alveolar collapse and inflammatory cells infiltration. Compared with LPS group, the destruction occurred in Dex groups were relieved in alveolar haemorrhage,interstitial oedema, alveolar collapse and inflammatory cells infiltration, especially in high-does Dex group, the degree of damage was the slightest.(5)The immunohistochemistry result showed that there were littles of NF-κB positive karyoplast in the airway tunica mucosa and interstitial lung in NS group, but the number of positive karyoplas were greatly increase in airway tunica mucos, interstitial lung, alveolar spaces and vascular endothelial cell after induced by LPS. With the increasing therapeutic Dex-does, the quantity of NF-κB positive karyoplas were obviously decrease compared with LPS group. The semiquantitative result also showed that the gray scale in high-and middle-does group were obvious decreased (p＜0.01), compared with LPS group.(6) The RT-PCR results showed that the quantity of expression with TLR4 mRNA were obviously increased in LPS group (P<0.01). Compared with LPS groups, the level of mRNA were obviously decreased in high-and middle-does groups (P＜0.05 or P＜0.01). Compared with YHB group, the level of mRNA were obviously decreased in high-does groups(P<0.01).Conclusion:Using high-and middle-does Dex can make the the organ/body coefficients and wet/dry ratios of decrease, protect the alveolar, relieve the interstitial edema and inflammatory cell infiltrate, down-regulate the IL-1β, IL-6 inflammatory factor, decrease the quaitity of expression in NF-κB protein and TLR4 mRNA, which can relieve the degree of ALI, having the effection of protecting lung.