| BackgroundsPremature birth rate increased significantly as a result of advanced maternal age, abnormal placenta (placental abruption, lead), bleeding, infection, preeclampsia, intrauterine growth retardation, abnormal prenatal findings, fetal hydrocephalus and many other factors. In recent years, it has been widely reported that premature morbidity and mortality rate are dramaticlly higher than that of full-term infants, and complicated respiratory disorders are the main reason. Therefore, treatment and prevention of preterm infants with respiratory diseases have become more and more urgent clinically.In1966, it was first reported by Avery that the delay of premature lung liquid absorption could lead to premature or wet lung in premature infants with respiratory distress syndrome, the symptom of which mainly includes shortness of breath after the birth, breathing difficulties and even respiratory failure. In normal conditions, although the alveoli is filled with liquid in the fetal period, when the head and thorax was squeezed through the narrow canal in the normal production process,, about1/2～2/3of the alveolar fluid is forced out through the mouth, and the rest is self-absorbed by interstitial pulmonary capillaries and lymphatic absorption. In recent years, however, with the increase of pregnant women during pregnancy complications and increase of fetal preterm cesarean delivery, the incidence of the respiratory distress increased remarkably owing to postnatal alveolar and interstitial fluid overload, delayed absorption, liquid transport disability. In these pathological conditions, the first24hours of alveolar liquid transport was retained and then gas exchange function was significantly impaired, which makes At present, the main method of intervention was application of dexamethasone through antenatal to promote lung liquid absorption. However, recent studies have found that long term effects of dexamethasone on the fetus is still unclear, which makes it impendent to explore new prevention methods for premature infants with the respiratory system diseases.It has been well known that β2-AR agonist could specifically excite pVAR. and play a role in relaxation of airway smooth muscle, reducing airway resistance, enhancing mucociliary clearance, inhibition of airway nerves, reducing vascular permeability, inhibition of mast cells and promoting inflammatory cells to release mediators. At present. β2-AR agonist, combined with inhaled corticosteroids. are used mainly for the treatment of respiratory tract and lung disease. Studies have found that terbutaline sulfate, a member of β2-AR agonist, could enhance alveolar epithelial fluid clearance in rat after acute lung injury and attenuate pulmonary edema with the result of improved gas exchange function. However, it is not clear yet so far whether the prenatal use of terbutaline sulfate could facilitate premature lung liquid absorption.PurposeTo observe the effects of terbutaline sulfate, a member of β2-AR agoniston lung liquid absorption in premature newborn rats, and analye its mechanism.MethodsPregnant rats were randomly divided into the following five groups in the study: pregnant sixteenth days after the start of drug intervention, by gavage for two times per day, once every3days. Rat pregnancy19days were taken from each group rats, newborn rats10, lung wet-to-dry weight ratio, Na+, K+-ATP enzyme activity and cyclic adenosine monophosphate (cAMP) concentration determination.Results1. Terbutaline sulfate decreased lung wet-to-dry weight ratio in ratThis study found that: simple premature rat lung wet-to-dry weight ratio was higher than that in normal controls (4.12±0.75vs.2.47±0.16, P<0.01), suggestive of herpes preterm group lung liquid absorption delay;0.013mg/kg terbutaline sulfate can reduce premature rat lung wet weight/dry weight ratio of (3.71±0.31vs.4.12±0.75, PO.01);0.025mg/kg terbutaline sulfate in the rat lung wet-to-dry weight ratio is lower than0.013mg/kg dose group (2.50±0.09v5.3.71±0.31, P<0.01), and compared with the normal control group without significant differences (2.50±0.09w.2.47±0.16, P>0.05); and the dexamethasone group (0.03mg/kg),0.025mg/kg terbutaline sulfate results slightly better (2.50±0.09vs.3.61±0.24. P<0.01). The results indicated terbutaline sulfate could promote the premature rat lung liquid absorption delay, and the effect may be slightly better than dexamethasone (Table1).2. Terbutaline sulfate increased Na, K+-ATP enzyme activity7of lung tissue in ratThis study found that simple in premature rat lung in Na+. K+-ATP activity was significantly lower than that in control group (61.45±6.02vs.103.58±10.47. P<0.01);0.013mg/kg terbutaline sulfate can be increased in premature rat lung tissues of Na+, K+-ATP enzyme activity (71±4.22vs.61.45±6.02. P<0.01);0.025mg/kg terbutaline sulfate can lead to premature rat lung tissues of Na+. K+-ATP enzyme activity compared with the normal control group showed no significant difference (103.58±10.47vs.103.58±10.47. P>0.05). indicating terbutaline sulfate group 2(0.025mg/kg), Na+, K+-ATP enzyme activity was close to normal; and dexamethasone group (100.06±10.78),0.025mg/kg terbutaline sulfate increased prematurity in lung tissue of rats with Na+, K+-ATP enzyme activity ability slightly stronger (110.9±11.60vs.100.06±10.78, P<0.05). The results indicated terbutaline sulfate may through increases in lung tissue of rats with Na+, K+-ATP enzyme activity to promote rat lung wet-to-dry weight ratio was lower (Table2).3. Determination of the cAMP concentration of lung in ratsThis research through observation of terbutaline sulfate is through increases in premature rat lung tissue cAMP concentrations to the activation of Na+, K+-ATP enzyme activity. Results: simple premature lung tissue were cAMP concentration was significantly lower than that in normal control group (1.87±0.09w.6.11±0.32, PO.01); O.OlBmg/kg terbutaline sulfate can be increased in premature rat lung tissues of Na+, K+-ATP enzyme activity (3.07±0.09vs.6.11±0.32, P<0.01);0.025mg/kg terbutaline could make pulmonary tissue cAMP concentrations compared with the normal control group showed no significant difference (6.11±0.32vs.6.20±0.11, P>0.05); and the dexamethasone group (0.03mg/kg),0.025mg/kg terbutaline sulfate increased prematurity in lung of rats with cAMP concentrations of capacity (6.11±0.32v5.4.45±0.18). The results indicated terbutaline sulfate may be achieved by adding a premature cAMP concentrations of rat lung tissue to the activation of Na+. K+-ATP enzyme activity.ConclusionIt was demonstrated in this study that the prenatal use of pVAR agonist, terbutaline sulfate, reduced the lung wet-to-dry weight ratio in premature newborn rat by promoting the lung liquid absorption in premature newborn rat. The effect of terbutaline sulfate is presumably braught about via elevated cAMP concentration and furthermore, increased Na+, K+-ATP enzyme activityin lung. The results of this study may provides new clues and novel experimental data for prevention and treatment of the liquid absorption delay in clinical practice. |
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