特非那丁对豚鼠肺组织β—受体向下调节影响的实验研究

应用放射配基结合分析法，分别测定了空白对照、沙丁胺醇（沙）、特非那丁（特）以及沙丁胺醇＋特非那丁（沙＋特）组豚鼠肺组织中β肾上腺素受体的βmax和Kd结果显示：（1）沙和特皆分别使β受体发生明显的向下调节。（2）沙＋特组β受体亲和力升高，并加剧受体向下调节，使其明显受抑。     

中药外敷治疗哮喘对β受体的影响

目的:探讨中药外敷治疗哮喘的作用机制。方法:采用Hutson法豚鼠模型,治疗组致敏豚鼠隔日诱喘后用中药敷贴30min,对照组隔日诱喘后采用9 g·L~(-1)NS溶液浸润纱布敷贴,2 wk后处死豚鼠,取肺组织;哮喘患者30例,发作期16例,缓解期14例,治疗前后取外周血,用放射配基竞争结合法比较豚鼠肺组织及患者外周血淋巴细胞β受体表达状态。结果:中药透皮治疗能上调哮喘豚鼠肺组织及患者外周血淋巴细胞β受体含量。结论:上调β受体含量可能是中药循经敷贴治疗哮喘的重要机制之一。     

β-受体激动剂加重洋地黄类药物心脏毒性

肾上腺素能神经β-受体激动剂及甲基黄嘌呤类药物在医疗上用于扩张支气管。新近以豚鼠与兔的离体心肌试验表明,洋地黄与茶碱联用可产生有害的效应。茶碱可增强洋地黄诱发心律失常的作用,以及抑制其正性肌力效应。特布他林(间羟舒喘宁,terbutaline)本身并不诱发心律失常,但可促使洋地黄诱发心律失常。洋地黄可产生延迟性后去极化。特布他林兴奋β受体,从而触发延迟性后去极化     

中药循经敷贴抗豚鼠实验性哮喘的作用机理初探

目的：探讨中药循经敷贴治疗哮喘的作用机理。方法：采用Hutson法豚鼠模型,治疗组隔日诱喘后用中药敷贴30min,对照组诱喘后隔日采用0．9％氯化钠溶液浸润纱布敷贴,比较记录诱喘潜伏期时间。2周后处死,取肺组织,用放射配基竞争结合法比较β受体含量。结果：中药循经敷贴能显著延长哮喘豚鼠诱潜伏期,减轻发作程度,上调哮喘豚鼠肺组织β受体含量。结论：二次实验结果提示,提高β受体含量是中药循经敷贴治疗哮喘的重要机制之一。     

孟鲁司特钠联合硫酸特布他林对老年支气管哮喘诱导痰细胞因子水平的影响

目的：观察孟鲁司特钠联合硫酸特布他林对老年支气管哮喘患者诱导痰细胞因子水平的影响。方法：以 2017 年 4 月—2019 年 10 月本院诊治的 126 例老年支气管哮喘患者为观察对象，随机分为孟鲁司特钠组、硫酸特布他林组、联合组， 每组 42 例。三组患者均予以常规治疗，孟鲁司特钠组单用孟鲁司特钠片，硫酸特布他林组单用硫酸特布他林片，联合组 则予以孟鲁司特钠片联合硫酸特布他林片，均连续服药 3 周。比较三组疗效及肺功能指标一秒用力呼气量（FEV1）和呼 气峰流速值（PEF），并检测诱导痰炎性介质白介素 -5（IL-5）、转化生长因子（TGF-β1）表达水平。结果：治疗后，无 效病例孟鲁司特钠组、硫酸特布他林组分别为 7 例、8 例，联合组 2 例，联合组疗效显著优于单一用药组（P＜0.05）；联 合组 FEV1、PEF 变化差值均显著高于单一用药组（P＜0.05）；联合组 IL-5、TGF-β1 差值均显著高于单一用药组（P＜0.05）。 结论：孟鲁司特钠联合硫酸特布他林可有效改善老年支气管哮喘肺功能，同时抑制炎症反应，其效果优于单一用药，有 助于患者恢复健康。     

白三烯受体拮抗剂对哮喘模型肺组织VEGF表达水平的影响

目的　探讨白三烯受体拮抗剂对哮喘模型肺组织血管内皮生长因子 (VEGF)表达的影响及其对哮喘模型气道重塑的预防和治疗作用 ,提供哮喘防治新途径的可靠实验依据。方法　 10 8只健康雄性豚鼠随机分为 3组 :哮喘发作组、治疗组、对照组 ,每组 36只。以卵蛋白 (OVA)致敏和激发建立豚鼠哮喘模型。肺组织病理切片以SP法免疫组化标记VEGF ,图像分析VEGF表达水平。结果　OVA激发后 4周 ,哮喘发作组肺组织VEGF表达水平显著高于治疗组及对照组 (P <0 0 5 ) ,白三烯受体拮抗剂治疗哮喘使肺组织VEGF的表达水平降低。结论　白三烯受体拮抗剂可以降低哮喘豚鼠肺组织VEGF表达水平 ,从而减少血管增生 ,延缓哮喘气道重塑的发生。     

孟鲁司特与布地奈德治疗儿童咳嗽变异性哮喘的临床观察

目的 观察孟鲁司特与布地奈德治疗儿童咳嗽变异性哮喘(CVA)的临床疗效.方法 97例CVA患儿随机分为孟鲁司特组与布地奈德组.孟鲁司特组予孟鲁司特、特布他林片口服治疗,布地奈德组予布地奈德气雾剂、特布他林气雾剂治疗.结果 孟鲁司特组总有效率91.7%,布地奈德组总有效率95.9%,两组疗效比较无显著性差异.结论 孟鲁司...     

孟鲁司特片联合特布他林片佐治支原体肺炎30例

目的 观察孟鲁司特片联合特布他林片佐治支原体肺炎的疗效.方法 选取60例支原体肺炎患者,随机均分为两组,对照组采用常规治疗,治疗组在常规治疗基础上加用孟鲁司特片及特布他林片.结果 治疗组疗效明显优于对照组,两组比较有显著性差异(P<0.01).结论 孟鲁司特片联合特布他林片佐治支原体肺炎疗效肯定,值得临床推广.     

β肾上腺素对大鼠急性肺动脉梗塞时肺脏水清除率的影响

目的探讨β肾上腺素对大鼠急性肺动脉栓塞时急性肺损伤的肺脏水清除率的影响。方法 30只SPF级SD大鼠,随机分为对照组、急性肺动脉梗阻4 h和24 h组,每组10只,建立大鼠左肺的急性肺动脉阻塞模型。分别测定左右肺的肺水容量、肺水清除率(AFC),应用β肾上腺素受体激动剂和抑制剂进一步调节发生变化的AFC,Real-time PCR方法测定β2肾上腺受体蛋白mRNA在大鼠肺组织中的表达。结果急性肺动脉阻塞4 h和24 h组的左肺AFC明显升高,肺动脉阻塞24 h后,肺水容量上升。但保持血液灌流的右肺无明显变化。β肾上腺素激动剂Terbutaline调节阻塞的左肺,各组AFC升高不明显,但β肾上腺素抑制剂propranolol可降低各组已经升高的肺水清除率。Real time PCR证实,4 h组和24 h组左肺β肾上腺素受体的mRNA水平升高。结论急性肺动脉栓塞可以引起大鼠阻塞肺肺水清除率的变化,在4 h升至顶峰,24 h略有下降。AFC的升高可能与β肾上腺素受体激活有关。     

布地奈德与硫酸特布他林超声雾化吸入联合孟鲁司特钠治疗小儿毛细支气管炎效果观察

目的 观察布地奈德与硫酸特布他林超声雾化吸入联合孟鲁司特钠治疗小儿毛细支气管炎的效果.方法 88例小儿毛细支气管炎随机分为对照组和治疗组,每组44例.两组均给予吸入用布地奈德混悬液0.5~1.0 mg、硫酸特布他林雾化液 1~5 mg加入0.9%氯化钠注射液5 ml超声雾化吸入,2/d;治疗组加服孟鲁司特钠4 mg,每晚1次.两组疗程均为7 d.观察两组临床症状、体征改善时间及住院时间,比较两组临床疗效和不良反应.结果 治疗组临床症状、体征改善和住院时间均较对照组短,治疗组总有效率为97.73%,高于对照组的86.36%,差异均有统计学意义(P＜0.05).两组均未发生明显不良反应.结论 布地奈德与硫酸特布他林超声雾化吸入联合孟鲁司特钠治疗小儿毛细支气管炎安全有效.     

Effect of azelastine on the down regulation of beta-adrenoceptors in guinea pig lung.

The new antiallergic drug azelastine (E-0659, Azeptin; CAS 58581-89-8) is used in the treatment of rhinitis and bronchial asthma. In the present study, the effect of azelastine on the regulation of the beta-adrenoceptors and the down regulation of beta-adrenoceptors by terbutaline, a beta-agonist, was investigated using guinea pig lungs. Guinea pigs were divided into four groups; (1) the control (saline-treated) group, (2) the terbutaline-treated group, (3) the azelastine-treated group, (4) terbutaline plus azelastine-treated group. Guinea pigs intramuscularly injected with each agent three times a day for successive 7 days. In the terbutaline-treated group, a 26% reduction in the number of beta-adrenoceptors compared with those of the control group was observed. In the azelastine-treated group, the number of beta-adrenoceptors increased by 24% compared with those of the control group. The number of the beta-adrenoceptors in the terbutaline plus azelastine-treated group was significantly increased compared with that of the terbutaline-treated group. These results suggest that azelastine may prevent the down regulation observed during beta-agonist administration by increasing the number of beta-adrenoceptors.     

Regulation of beta-adrenoceptors in the guinea pig left ventricle and skeletal muscle following chronic agonist treatment

Pretreatment of guinea pigs with adrenaline, isoprenaline or terbutaline for 7 days significantly reduced the Bmax for the radioligand [125I]cyanopindolol (ICYP) in the gastrocnemius muscle (beta 2-adrenoceptors). Pretreatment of guinea pigs with terbutaline reduced the responsiveness of gastrocnemius muscle slices adenylate cyclase to isoprenaline (10(-4) M). In the left ventricle (predominantly beta 1-adrenoceptors) pretreatment of guinea pigs with isoprenaline or adrenaline for 7 days did not alter the Bmax for ICYP. The responsiveness of adenylate cyclase to isoprenaline (10(-4) M) in left ventricle slices was significantly reduced following isoprenaline pretreatment of the guinea pigs. Thus desensitisation of beta-adrenoceptors in left ventricle and skeletal muscle developed following chronic agonist pretreatment. Reduction of beta 2-adrenoceptors in the skeletal muscle could be responsible for the desensitisation of adenylate cyclase. In the left ventricle the receptors were resistant to agonist induced down-regulation. It is proposed that other mechanisms which are tissue- and species-specific independent of the receptor subtype can be responsible for agonist-induced desensitisation in the left ventricle of the guinea pig in vivo.     

Haemophilus influenzae induced loss of lung beta-adrenoceptor binding sites and modulation by changes in peripheral catecholaminergic input

Vaccination of guinea pigs with killed suspensions of Haemophilus influenzae, a bacterium often found in the deeper respiratory airways of asthmatic bronchitics, results in a number of effects suggesting an impairment of beta-adrenoceptor function. A [3H]dihydroalprenolol binding assay was used to determine the number of beta-adrenoceptors (Bmax) following H. influenzae vaccination. The Bmax declined significantly by 29% from 1240 +/- 80 to 880 +/- 70 fmol/mg protein, while the binding affinity of the sites was not changed. Specific binding in the presence of 1.8 nM [3H]DHA to tracheal longitudinal smooth muscle was also significantly lower in H. influenzae-vaccinated animals as compared to controls. Furthermore modulation of peripheral sympathetic input to lung beta-adrenoceptors was evaluated in our model. Pretreatment with Ro4-4602, an inhibitor of dopa-decarboxylase, increased the number of beta-adrenoceptors and prevented the H. influenzae-induced loss of beta-adrenoceptors. On the other hand repeated doses of the antidepressant desipramine mimicked the effect of H. influenzae vaccination i.e. a loss of beta-adrenoceptors. Desipramine and H. influenzae vaccination were not synergistic in their effects. The effects of H. influenzae and modulation of catecholaminergic input on guinea pig lung beta-adrenoceptors were compared with tracheal strip relaxation by isoproterenol, following similar treatments assessed in a superfusion model. Changes in lung beta-adrenoceptor number were almost identical with changes in tracheal strip relaxation. These results suggest that compensatory regulation adapts the number of respiratory beta-adrenoceptors to changes in sympathetic input. A similar mechanism may underlie the loss of beta-adrenoceptors following H. influenzae vaccination.     

鱼棉平喘方对哮喘豚鼠的平喘作用及血清总IgE含量的影响

采用观察各组豚鼠给药前、后的引喘潜伏期及血清总IgE含量变化的方法对鱼棉平喘方进行了研究.结果显示本方有明显的平喘作用.本方给药后各组豚鼠的引喘潜伏期比给药前及纯化水组均显著延长(P＜0.01),与蛤蚧定喘胶囊组比较无显著性差异(P＞0.05);本方治疗各组血清总IgE含量比模型组显著降低(P＜0.01),与正常组及蛤蚧定喘胶囊组无显著差异(P＞0.05),说明本方有明显的平喘作用,其平喘作用与降低哮喘模型豚鼠异常升高的血清IgE水平,参与机体的免疫调节作用有关.     

Alloimmunization-induced changes in beta-adrenoceptor expression and cAMP on B lymphocytes

In this report we have examined the effect of alloimmunization on beta-adrenergic expression in lymphocytes. We have observed a variation in the number of beta-adrenoceptors (Bmax) according to the degree of immunization without modifications in their affinity (Kd). This phenomenon was accompanied with parallel variations of intracellular cAMP levels. A decrease in Bmax values was observed during the first and second immunizations. Then the Bmax began to increase, exceeding control values up to the fourth and fifth immunizations, and remaining constant at the sixth immunizations. Only B cell-enriched populations showed variation in Bmax values of beta-adrenoceptors with alloimmunization. In contrast, the Bmax values of T cell-enriched populations did not change. Kd values were similar in all cell types tested. The number of binding sites was not dependent on the animal's age. Modifications in cAMP levels of B cell-enriched populations were correlated with changes in beta-adrenoceptor expression. These results suggest that beta-adrenoceptor expression and cAMP intracellular levels in B cell-enriched populations vary with the number of alloimmunizations. In addition, the antibody synthesis induced by allogenic stimulus was inversely proportional to the number of beta-adrenoceptors expressed on B cells. Perhaps these findings are evidence of a control mechanism that regulates antibody synthesis during the immune response.     

Concomitant glucocorticoid treatment prevents the development of beta-adrenoceptor desensitization in the guinea pig lung

The aim of the present study was to investigate, whether concomitant administration of the synthetic glucocorticoid betamethasone (BM), theophylline (THEO), or the muscarinic antagonist ipratropium bromide (IPRA) could influence the desensitization-associated decrease of beta-adrenoceptors in the guinea pig lung during prolonged in vivo treatment with the beta 2-agonist terbutaline (TER). The animals were sacrificed 20 hrs after the last drug dosage and the lung membrane homogenates were prepared for 3H-dihydroalprenolol (3H-DHA) binding in vitro. Treatment with TER 200 micrograms/kg subcutaneously twice a day for five days decreased by 22% the maximum number of binding sites (Bmax) at saturation in comparison with the saline-treated controls. Concomitant administration of BM 2 mg/kg intraperitoneally abolished this effect of TER, whereas THEO 20 mg/kg or IPRA 5 micrograms/kg failed to modify it. None of the in vivo treatments affected the binding affinity of 3H-DHA. In vitro, TER inhibited in a concentration-dependent manner 3H-DHA binding to the lung membranes of untreated guinea pigs. At high concentrations IPRA, but not THEO or BM, showed some binding to the beta-receptors as well. Thus, it is concluded that glucocorticoids may prevent beta-adrenoceptor desensitization in the lungs via an indirect mechanism, e.g. inhibition of phospholipase A2 enzyme.     

火把花根片对哮喘豚鼠抗炎机制及其对肺泡灌洗液IL-5受体mRNA表达的影响

目的　探讨火把花根片对哮喘豚鼠抗炎作用机制及其对肺泡灌洗液 (BALF)白介素 5(IL 5)受体mRNA表达的影响。方法　 3 2只健康豚鼠随机分为 4组 :正常对照组 ,哮喘组 ,地塞米松治疗组 ,火把花根片治疗组。后 3组制作成哮喘豚鼠模型 ,再激发用药。测定肺泡灌洗液的细胞总数和细胞分类 ,观察肺组织的病理改变 ,进行BALF的IL 5受体mRNART PCR半定量分析。结果　火把花根片治疗组BALF的嗜酸性粒细胞 (Eos)数较正常组和哮喘组 ,差异均有显著性 ,分别为P <0 0 5和P <0 0 1。肺组织病理切片 ,火把花根片组充血水肿明显 ,但Eos肺组织浸润较哮喘组有明显减少。BALF的IL 5受体mRNART PCR半定量分析显示 ,火把花根片治疗组与地塞米松治疗组差异无显著性 ,P >0 0 5,但和正常组与哮喘组比较差异有显著性 ,P <0 0 1。结论　火把花根片能抑制哮喘豚鼠的气道炎症 ,为临床治疗哮喘提供初步的理论基础     

Effects of chemical sympathectomy with 6-hydroxydopamine on alpha- and beta-adrenoceptors and muscarinic cholinoceptors in rat kidney

The autonomic receptors in the rat kidney were characterized using the radioligands [3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol (DHA) and [3H]quinuclidinyl benzilate (QNB). The specific binding of [3H]prazosin, [3H]clonidine, [3H]DHA and [3H]QNB to rat kidney membranes was saturable and of high affinity, and showed a pharmacological specificity as well as stereospecificity which characterized renal alpha 1-, alpha 2- and beta-adrenoceptors and muscarinic cholinoceptors, respectively. There was a relatively greater density of alpha-adrenoceptors than beta-adrenoceptors or muscarinic cholinoceptors in the rat kidney. Chemical sympathectomy of rats with 6-hydroxydopamine X HBr (6-OHDA, 50 X 2 mg/kg i.v., 24 h interval) caused a significant increase (21-56%) in the Bmax values for renal [3H]prazosin, [3H]clonidine and [3H]DHA binding at 1 and 2 weeks following the treatment, without a change in the Kd values. 6-OHDA treatment had no significant effect on the Kd and Bmax values for [3H]QNB binding at 1-3 weeks after the treatment. The norepinephrine (NE) concentration was reduced (68-76%) in the 6-OHDA-treated rat kidney. In conclusion, the present study provides biochemical evidence for the possible localization of postsynaptic alpha 1-, alpha 2- and beta-adrenoceptors and muscarinic cholinoceptors in the rat kidney and also for the regulation of these adrenoceptors by the sympathetic nervous system.     

Histoautoradiographic localization of (-)-3H-dihydroalprenolol in rabbit aorta

The distribution pattern of (-)-3H-dihydroalprenolol (3H-DHA) binding sites within the thoracic and abdominal aorta was studied using a histoautoradiographic technique. Frozen sections of rabbit aorta were incubated with 3H-DHA in the presence or absence of 1 mumol/l (-)-propranolol and of increasing concentrations of various adrenergic agents. After washing, the same secretions were placed in scintillation vials and counted to evaluate the pharmacological characteristics of 3H-DHA binding or processed for histoautoradiography. 3H-DHA was bound by sections of the rabbit aorta in a manner consistent with the presence of beta-adrenoceptors. The binding was reversible, saturable and of high affinity, with a dissociation constant Kd of 1.0 nmol/l and a maximum binding capacity Bmax of 17 fmol/mg tissue (wet weight). It was inhibited only by beta-adrenoceptor blocking drugs. Histoautoradiographic studies revealed that beta-adrenoceptors are located primarily in the media and then in the intima. The lowest density of 3H-DHA was found in the adventitia. The distribution pattern of beta-adrenoceptors in the media suggests the possible existence of two groups of beta-adrenoceptors within this layer of the aorta. The first group was found in the outer portions of the media and may be controlled by the adrenergic nerves that supply the artery. The second group was found in the portions of the media closest to the intima and is likely under the control of catecholamines coming from the lumen of the aorta.     

Regulation of beta 1- and beta 2-adrenoceptors following chronic treatment with beta-adrenoceptor antagonists

The effect of chronic pretreatment of guinea pigs with various beta-adrenoceptor antagonists on the binding characteristics of the radioligand 125I-cyanopindolol (ICYP) and responsiveness of adenylate cyclase to isoprenaline in the gastrocnemius muscle (beta 2-adrenoceptors) and the left ventricle (beta 1-adrenoceptors) were compared. Pretreatment of guinea pigs with propranolol or ICI 118,551 for one week significantly increased the density of the beta 2-adrenoceptors in the gastrocnemius muscle. Atenolol pretreatment for one week did not affect the density of the receptors. Pretreatment of the animals with pindolol for one week reduced the density of beta 2-adrenoceptors in skeletal muscle. In the left ventricle pretreatment of the guinea pigs with any of the antagonists did not alter either the density or the KD of beta 1-adrenoceptors. The responsiveness of adenylate cyclase to isoprenaline (10(-4) M) in the left ventricle or skeletal muscle was not affected when the guinea pigs were pretreated with propranolol. Pretreatment of the guinea pigs with reserpine (0.5 mg.kg-1) intraperitoneally for one week, to deplete catecholamines did not affect beta-adrenoceptor density or KD in the left ventricle or skeletal muscle. We conclude that the regulation of beta-adrenoceptors by the antagonist may not be caused by the prevention of the access of endogenous agonists to beta-adrenoceptors and it is dependent on the selectivity of the antagonist and on the susceptibility of the receptors to regulation.