本文選題：早產(chǎn)大鼠 + 肺液轉(zhuǎn)運(yùn)　； 參考：《山西醫(yī)科大學(xué)》2012年碩士論文

【摘要】：研究背景 孕產(chǎn)婦高齡、異常胎盤(胎盤早剝、前置)、出血、感染、先兆子癇、宮內(nèi)生長遲緩、異常的產(chǎn)前征象、胎兒腦積水等諸多因素均可導(dǎo)致早產(chǎn)兒出生率明顯增高。近年來,早產(chǎn)兒的病死率和患病率明顯高于足月兒,而呼吸道疾病是較為常見的并發(fā)癥。因此,治療及預(yù)防早產(chǎn)兒呼吸系統(tǒng)疾病已經(jīng)成為臨床上需要解決的主要問題之一。 1966年,Avery首次報(bào)道：早產(chǎn)兒肺液吸收延遲可導(dǎo)致早產(chǎn)兒濕肺或早產(chǎn)兒呼吸窘迫綜合征,主要表現(xiàn)為出生后氣促、呼吸困難甚至呼吸衰竭。胎兒時期肺泡內(nèi)充滿液體,在正常生產(chǎn)過程中需要通過狹窄的產(chǎn)道,當(dāng)頭部娩出而胸廓受擠壓時約有1/2-2/3的肺泡液經(jīng)口、鼻排出體外,其余部分由肺間質(zhì)毛細(xì)血管和淋巴管吸收自行吸收。然而,近年來隨著孕婦孕產(chǎn)期合并癥的增加,使胎兒未足月行剖宮產(chǎn)娩出大量增多,生后肺泡內(nèi)及間質(zhì)內(nèi)液體過多,吸收延遲,或有液體運(yùn)轉(zhuǎn)困難,以致出生24小時內(nèi)肺泡存留較多液體而影響氣體交換,這就使呼吸窘迫綜合征的發(fā)生率大大增加。 臨床上早已在產(chǎn)前使用地塞米松來預(yù)防早產(chǎn)兒呼吸窘迫綜合征的發(fā)生。然而,經(jīng)產(chǎn)前地塞米松治療雖然在很大程度上達(dá)到預(yù)防呼吸窘迫綜合征的目的,但尚不能完全預(yù)防,且可能對胎兒會產(chǎn)生遠(yuǎn)期影響。因此還需尋求更積極的方法來預(yù)防早產(chǎn)兒的呼吸系統(tǒng)疾病。 由于β2-AR激動劑能特異性興奮p2-AR,發(fā)揮松弛氣道平滑肌、降低氣道阻力、增強(qiáng)黏液纖毛清除、抑制氣道神經(jīng)、降低血管通透性、抑制肥大細(xì)胞、炎性細(xì)胞釋放介質(zhì)。目前,臨床上主要聯(lián)合吸入皮質(zhì)激素與β2-腎上腺素受體(β2-Adrenergic receptor, β2-AR)激動劑治療小兒呼吸道與肺部疾病。已有研究發(fā)現(xiàn)：硫酸特布他林可增強(qiáng)急性肺損傷后大鼠肺泡上皮液體清除功能,減輕肺水腫,從而改善氣體交換功能。然而,產(chǎn)前使用硫酸特布他林是否可以促進(jìn)早產(chǎn)兒肺液吸收并不清楚。 目的 觀察β2-AR激動劑硫酸特布他林對早產(chǎn)新生大鼠肺液吸收的影響,并分析其作用機(jī)制。 方法 本研究將孕鼠隨機(jī)分為以下5組：受孕后第16天開始干預(yù),藥物均采用灌胃方法,1日2次,連用3天。大鼠孕19天殺鼠取材,每組取新生鼠10只,進(jìn)行肺組織濕重/干重之比、Na+,K+-ATP酶活性和環(huán)磷酸腺苷(cAMP)濃度測定。 結(jié)果 1.硫酸特布他林促進(jìn)大鼠肺組織濕重/干重比值降低 本研究發(fā)現(xiàn)：單純早產(chǎn)組大鼠肺組織濕重/干重比值高于正常對照組(4.12±0.75vs.2.47±0.16,P0.01),提示單純早產(chǎn)組肺液吸收延遲；0.013mg/kg硫酸特布他林可以降低早產(chǎn)大鼠肺組織濕重/干重比值(3.71±0.31vs.4.12±0.75,P0.01)；0.025mg/kg硫酸特布他林使得大鼠肺組織濕重/干重比值低于0.013mg/kg劑量組(2.50±0.09vs.3.71±0.31,P0.01),且與正常對照組相比無顯著性差異(2.50±0.09vs.2.47±0.16,P0.05)；與地塞米松組(0.03mg/kg)相比,0.025mg/kg硫酸特布他林的效果略好(2.50±0.09vs.3.61±0.24,P0.01)。以上結(jié)果提示：硫酸特布他林可以促進(jìn)早產(chǎn)大鼠肺液吸收延遲,且效果可能略優(yōu)于地塞米松(見表1)。 2.硫酸特布他林促進(jìn)大鼠肺組織Na+,K+-ATP酶活性增加 本研究發(fā)現(xiàn)：單純早產(chǎn)大鼠肺組織中的Na+,K+-ATP酶活性顯著低于正常對照組(61.45±6.02vs.103.58±10.47,P0.01)；0.013mg/kg硫酸特布他林可以增加早產(chǎn)大鼠肺組織Na+,K+-ATP酶活性(71.0±4.22vs.61.45±6.02,P0.01)；0.025mg/kg硫酸特布他林可使早產(chǎn)大鼠肺組織Na+,K+-ATP酶活性與正常對照組之間無統(tǒng)計(jì)學(xué)差異(103.58±10.47vs.103.58±10.47,P0.05),表明硫酸特布他林組2(0.025mg/kg) Na+, K+-ATP酶活性已接近正常；與地塞米松組(100.06±10.78)相比,0.025mg/kg硫酸特布他林增加早產(chǎn)大鼠肺組織中Na+,K--ATP酶活力的能力略強(qiáng)(110.9±11.60vs.100.06±10.78,P0.05)。以上結(jié)果提示：硫酸特布他林可能通過增加大鼠肺組織中Na+,K+-ATP酶活性來促進(jìn)大鼠肺組織濕重/干重比值降低(見表2)。 3.硫酸特布他林促進(jìn)大鼠肺組織cAMP濃度增加 本研究通過觀察硫酸特布他林是否通過增加早產(chǎn)大鼠肺組織中cAMP濃度來激活Na+,K+-ATP酶活性。結(jié)果發(fā)現(xiàn)：單純早產(chǎn)組肺組織cAMP濃度明顯低于正常對照組(1.87±0.09vs.6.11±0.32, P0.01):0.013mg/kg硫酸特布他林可以增加早產(chǎn)大鼠肺組織Na+,K+-ATP酶活性(3.07±0.09vs.6.11±0.32,P0.01)；0.025mg/kg特布他林可使肺組織cAMP濃度與正常對照組相比無統(tǒng)計(jì)學(xué)差異(6.11±0.32vs.6.20±0.11,P0.05)；與地塞米松組(0.03mg/kg)相比,0.025mg/kg硫酸特布他林增加早產(chǎn)大鼠肺組織中cAMP濃度的能力更強(qiáng)(6.110.32vs.4.45±0.18)。以上結(jié)果提示：硫酸特布他林可能通過增加早產(chǎn)大鼠肺組織中cAMP濃度來激活Na+,K+-ATP酶活性。 結(jié)論 本研究發(fā)現(xiàn)：產(chǎn)前使用β2-AR激動劑硫酸特布他林,可以降低早產(chǎn)新生大鼠肺組織濕重/干重之比,即促進(jìn)早產(chǎn)新生大鼠肺液吸收；該效應(yīng)可能是硫酸特布他林通過升高肺組織中cAMP濃度進(jìn)而增加Na+,K+-ATP酶活性引起的。這一研究結(jié)果為臨床預(yù)防早產(chǎn)兒發(fā)生肺液吸收延遲提供了新的思路和實(shí)驗(yàn)依據(jù)。
[Abstract]:Research background
Maternal age, abnormal placenta (placenta abruption, preposition), bleeding, infection, preeclampsia, intrauterine growth retardation, abnormal antenatal signs, fetal hydrocephalus and many other factors can lead to a significant increase in the birth rate of preterm infants. In recent years, the mortality and prevalence of premature infants are significantly higher than those in the full-term infants, and respiratory diseases are more common complications. Therefore, the treatment and prevention of respiratory diseases in premature infants has become one of the major problems that need to be solved clinically.
In 1966, Avery first reported that the delayed absorption of pulmonary fluid in preterm infants could lead to premature infant wet lung or premature infant respiratory distress syndrome, mainly manifested in postnatal, respiratory and respiratory failure. In the fetal period, the alveoli are filled with liquid and need to pass through a narrow birth canal in normal production, when the head is delivered and the chest is squeezed. About 1/2-2/3 of the alveolar fluid is passed through the mouth, the nose is discharged from the body, the rest is absorbed by the pulmonary capillary capillary and the lymphatic vessels. However, in recent years, with the increase of pregnancy and birth complications in pregnant women, there is a large increase in the childbirth of the fetus without full term cesarean section, excessive fluid in the alveoli and interstitial fluid after birth, delayed absorption, or difficult fluid operation. That is to say, the presence of more fluid in alveoli and gas exchange during the 24 hours of birth will increase the incidence of respiratory distress syndrome.
Dexamethasone has long been used to prevent the occurrence of premature infant respiratory distress syndrome. However, prepartum dexamethasone is not fully prevented and may have a long effect on the fetus, although it is to a large extent the purpose of preventing respiratory distress syndrome. Prevention of respiratory diseases in preterm infants.
Due to the specific excitatory effect of beta 2-AR agonist on p2-AR, it relaxes airway smooth muscle, reduces airway resistance, enhances mucociliary clearance, inhibits airway nerve, reduces vascular permeability, inhibits mast cells, and releases mediators of inflammatory cells. At present, the main clinical combination of inhaled skin hormone and beta 2- adrenergic receptor (Beta 2-Adrenergic receptor) Beta 2-AR) agonists have been used to treat respiratory and pulmonary diseases in children. It has been found that terbutaline sulfate can enhance the fluid clearance function of alveolar epithelium in rats after acute lung injury, reduce pulmonary edema, and improve gas exchange function. However, it is not clear whether prenatal use of terbutaline can promote the absorption of pulmonary fluid in premature infants.
objective
To observe the effect of terbutaline sulfate, a beta 2-AR agonist, on the absorption of pulmonary fluid in preterm newborn rats and analyze its mechanism.
Method
In this study, pregnant rats were randomly divided into 5 groups: the intervention of sixteenth days after pregnancy and the use of gavage, 1 days 2 times and 3 days. The rats were selected for 19 days of pregnancy and 10 newborn rats in each group were selected, and the ratio of wet weight / dry weight of lung tissue, the activity of Na+, K+-ATP enzyme and the concentration of cAMP were measured.
Result
1. terbutaline sulfate increased the ratio of wet weight to dry weight of lung tissue in rats.
The study found that the ratio of wet weight / dry weight of lung tissue in preterm preterm rats was higher than that of normal control group (4.12 + 0.75vs.2.47 + 0.16, P0.01), suggesting that pulmonary fluid absorption delayed in preterm labor group; 0.013mg/kg sulfate terbutaline could reduce the ratio of wet weight / dry weight (3.71 + 0.31vs.4.12 + 0.75, P0.01) in preterm rats and 0.025mg/kg sulphate. The ratio of wet weight / dry weight of rat lung tissue was lower than that of 0.013mg/kg dose group (2.50 + 0.09vs.3.71 + 0.31, P0.01), and there was no significant difference compared with the normal control group (2.50 + 0.09vs.2.47 + 0.16, P0.05). Compared with dexamethasone group (0.03mg/kg), the effect of 0.025mg/kg terbutaline was slightly better than that of 0.025mg/kg (2.50 + 0.09vs.3.61 + 0.24, P0.01). The results suggest that terbutaline sulfate can promote the delayed absorption of lung fluid in premature rats, and the effect may be slightly better than that of dexamethasone (see Table 1).
2. terbutaline sulfate increased the activity of Na+ and K+-ATP in lung tissue of rats.
This study found that the Na+, K+-ATP enzyme activity in the lung tissue of preterm rats was significantly lower than that in the normal control group (61.45 + 6.02vs.103.58 + 10.47, P0.01); 0.013mg/kg sulfate terbutaline could increase the Na+, K+-ATP enzyme activity (71 + 4.22vs.61.45 + 6.02, P0.01) of the lung tissue of preterm rats; 0.025mg/kg sulfate terbutaline could make the lung of premature rats lung There was no statistical difference between the tissue Na+, K+-ATP enzyme activity and normal control group (103.58 + 10.47vs.103.58 + 10.47, P0.05), indicating that the activity of 2 (0.025mg/kg) Na+, K+-ATP enzyme activity of the terbutaline sulfate group was close to normal; compared with the dexamethasone group (100.06 + 10.78), 0.025mg/ kg sulfate terbutaline increased Na+, K--ATP enzyme activity in the lung tissue of preterm rats The ability of force was slightly stronger (110.9 + 11.60vs.100.06 + 10.78, P0.05). The above results suggest that terbutaline sulfate may promote the decrease of wet weight / dry weight ratio of lung tissue in rat lung by increasing the activity of Na+ and K+-ATP in rat lung tissue (see Table 2).
3. terbutaline sulfate increased cAMP concentration in lung tissue of rats
The purpose of this study was to observe whether terbutaline sulfate activated Na+ and K+-ATP enzyme activity by increasing the concentration of cAMP in the lung tissue of preterm rats. The results showed that the concentration of cAMP in the lung tissue in the simple preterm group was significantly lower than that of the normal control group (1.87 + 0.09vs.6.11 + 0.32, P0.01): 0.013mg/kg sulfate terbutaline could increase the Na+ of the lung tissue of the preterm rats, K+-AT The activity of P enzyme (3.07 + 0.09vs.6.11 + 0.32, P0.01); 0.025mg/kg in terbutaline could make the cAMP concentration of lung tissue have no statistical difference (6.11 + 0.32vs.6.20 + 0.11, P0.05). Compared with dexamethasone group (0.03mg/kg), 0.025mg/kg sulfate terbutaline increased the ability of cAMP concentration in the lung tissue of premature rats (6.110.32vs.4) .45 + 0.18). These results suggest that terbutaline sulfate may activate Na+ and K+-ATP enzyme activities by increasing the cAMP concentration in the lung tissue of premature rats.
conclusion
This study found that prenatal use of terbutaline, a beta 2-AR agonist, can reduce the ratio of wet weight / dry weight of lung tissue in premature newborn rats, that is, promoting pulmonary fluid absorption in premature newborn rats; this effect may be caused by the increase of the concentration of cAMP in the lung tissue by terbutaline sulfate and the increase of the activity of Na+ and K+-ATP enzyme. It provides a new idea and experimental basis for clinical prevention of premature pulmonary fluid absorption delay.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R722.6

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