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The Mechanism Of Action About Propofol On Isolated Tracheal Smooth Muscle Of Rabbit

Posted on:2011-06-04Degree:MasterType:Thesis
Country:ChinaCandidate:Y G XuFull Text:PDF
GTID:2154360308974407Subject:Anesthesia
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Objectives:Propofol is most commonly used intravenous anesthetics, it has been widely applied in patients sedation in general anesthesia and ICU. In addition to anesthesia and sedative effects, propofol also has an effect of relaxing blood vessels and tracheal smooth muscle. Currently, the report about tension of airway smooth muscleshow that propofol has relaxing affects on airway smooth muscle both in vivo and vitro.Studies suggest that clinical concentrations of propofol, possibly relax bronchial smooth muscle indirectly by reducing the excitability of the vagus nerve, however, propofol of high concentrations can be a direct relaxation of bronchial smooth muscle. Airway smooth muscle usually be in a relatively quiescent state and only maintain a slight tension. This resting tension maintained by acetylcholine which was released by the nerve in airway smooth muscle. When the signals from extracellular biological and cell surface receptors were combined, it will start a specific signaling pathway to complete information transfer, causing contraction orrelaxation of smooth muscle. There have clinical trials show that in the process of induction of anesthesia and tracheal intubation, especially for certain special populations; such as asthma, airway hyper-responsiveness of patients and so on, propofol has certain protection role in airway, it can inhibit the anesthesia induction and bronchoconstriction caused by intubation. Caveolae is a specialized cell membrane structures, mainly composed of proteins and lipids, which participate in transmembrane transport, it was a hub rich in cell signaling molecules and signal transduction.Caveolin (caveolin-1) is the major elements in structural part and regulatory part. Recent studies have shown that caveolin play an important role in the contraction of airway smooth cells. At present, the mechanism of propofol causing airway relaxation, especially under the statement of inflammatory, is still being explored. This study through the use of isolated rabbit tracheal smooth muscle strips to explore the mechanism of high concentration of propofol in normal and inflammatory state whether by changing signal path to reduce the expression effect of caveolin (caveolin-1).Methods:Six healthy rabbits, rats were killed with air embolism, each rabbit tracheal smooth muscle strips in preparation 8, based on tracheal smooth muscle strips hanging in the nutrient solution in dealing with different factors to tracheal smooth muscle strips that were divided into 8 groups: group A (0umol / L), group B (propofol 300umol / L), group C (CD-β10mmol / L), group D (CD-β10mmol / L + propofol 300umol / L), group E (0umol / L), group F (propofol 300umol / L), group G (CD-β10mmol / L), group H (CD-β10mmol / L + propofol 300umol / L). E, F, G, H four tracheal smooth muscle strips immersed in pre-need with a good concentration of 50ng/mlTNF-a in solution, and pass with 95% O2 and 5% CO2 at 4℃refrigerator temperature for 12 hours for testing. Each tracheal strip to a second experiment, do not reuse, tracheal end fixed to the double-sandwich muscle isolated organ groove of the bottom of the thermostat, connect the other end of the transducer, the bath plus 5m1 Krebs-Henseleit nutrient solution (K-H solution) , and the tracheal rings connected by force - displacement transducers recorded tension changes in load balance and stability increase 1g 2h before you can experiment, given the concentration of 1μM / L acetylcholine (Ach) stimulated tracheal smooth muscle strips until the tension reached its peak when the value of tension values recorded in each group (T0 = 0s), then washed three times with KH medium to Ach clean, with different reagents, and recorded at different time points (T1 = 30s, T2 = 5min, T3 = 30min, T4 = 60min) the tension value. After the end of the experiment three times with KH solution flushing, testing samples with acetylcholine activity, no activity were abandoned. 10% of the final specimens were fixed in formalin, measured by immunohistochemistry the expression of caveolin-1 protein. Results:1. H-E staining showed that each group were relatively intact smooth muscle cells, spindle cell nucleus in blue, red extracellular matrix for the spindle, see Fig1-8.2. Group A of caveolin-1 protein expression as high (+++); Group B the expression of caveolin-1 protein, low expression (+); Groups C, D caveolin-1 protein expression (-).3. Group E caveolin-1 protein expression as high (+++); Group F low caveolin-1 protein expression (+); Groups G, H caveolin-1 expression was (-).1. Compared with A B, C, D group T1-4 time tension values decreased significantly (P <0.05); compared with B C, D T1-4 time points, two tension values high, the difference was statistically significant (P <0.05); compared with T0, B, C, D T1-4 three time points of tension values were reduced significantly (P <0.05).4. Compared with the E F, G, H group T1-4 time points, tension is reduced, the differences were statistically significant (P <0.05); compared with F G, H groups T1-4 time points of tension values high, the difference was statistically significant (P <0.05); compared with T0, F, G, H three time points T1-4 tension values were reduced significantly (P <0.05); F group than in the B Group T1-4 time points was significantly reduced tension, the difference was statistically significant (P <0.05).Conclusions: 1. Propofol obvious tracheal smooth muscle, the mechanism of inhibition of caveolin expression.2. Propofol on inflammatory status of the airway smooth muscle relaxation has a significant role.3.β-cyclodextrin (β-Cyclodextrin;β-CD) on tracheal smooth muscle relaxing effect is weak.
Keywords/Search Tags:Propofol, Tracheal smooth muscle, Caveolin-1, inflammation, Cyclodextrin
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