气道高反应性测定用于咳嗽变异型哮喘诊断

目的 探讨气道高反应性测定在咳嗽变异型哮喘诊断中的临床价值。方法 78例以咳嗽及无明显原因胸闷为主要临床表现疑诊支气管哮喘患者,吸入组胺做支气管激发试验,测定其气道反应性。结果 78例患者中组胺支气管激发试验阳性46例,阳性率58．97％。46例气道高反应性患者中重度3例,占6．52％;中度8例,占17．39％;轻度18例,占39．13％;极轻度17例,占36．96％。结论 通过气道高反应性测定可对咳嗽变异型哮喘作出早期诊断,气道高反应性是诊断哮喘的必备条件。     

6%氯化钠用于支气管高反应性测定的临床观察

气管高反应性是哮喘的特征 ,测定支气管高反应性对哮喘的诊断十分重要。以往药物激发试验广泛应用于支气管高反应性测定 ,但对大量人群调查结果显示 ,组胺、乙酰胆碱激发试验特异性低 ,用高渗盐水吸入激发不仅特异性高 ,而且敏感性也令人满意[1] 。我科于 1997年 1月至 1999年 6月应用 6%氯化钠对轻、中度支气管哮喘病人和健康志愿者各 40例进行支气管反应测定 ,效果满意 ,报告如下。1　资料与方法1 1　病例选择　哮喘组 (观察组 )和健康志愿者组 (对照组 )各 40例 ,两组男女比例分别为 2 6∶14和 2 8∶12 ;年龄分别为3 3± 15岁和 3 1± 12…     

小剂量罗红霉素对支气管哮喘患者气道高反应性的影响

目的:观察小剂量罗红霉素对支气管哮喘患者气道高反应性的影响。方法:48例支气管哮喘患者按随机数字表法分为观察组(22例)和对照组(26例)。两组患者均给予吸入用布地奈德混悬液0.25 mg,bid;吸入用硫酸沙丁胺醇溶液200μg,bid;氨茶碱0.25 g加入5%葡萄糖注射液250 ml中静脉滴注,bid。连用3 d后,根据症状改善情况,对照组患者停用氨茶碱,并按需要调整布地奈德混悬液和硫酸沙丁胺醇溶液的剂量;观察组患者停用氨茶碱,加服罗红霉素100 mg,bid。两组患者疗程均为15 d。观察两组患者治疗前后第1秒用力呼气量(FEV1)、FEV1占预计值的百分率(FEV1%)、最大呼气流速(PEF)、白介素(IL)-2、IL-4、IL-5、干扰素(INF)-γ、1型辅助T细胞(Th1)、2型辅助T细胞(Th2)、Th1/Th2及不良反应发生情况。结果:治疗前两组患者肺功能指标、炎性因子水平、Th1、Th2、Th1/Th2比较,差异均无统计学意义(P>0.05)。治疗后两组患者肺功能指标、IL-2、INF-γ、Th1、Th1/Th2均显著高于同组治疗前,且观察组显著高于对照组;IL-4、IL-5、Th2均显著低于同组治疗前,且观察组显著低于对照组,差异均有统计学意义(P<0.05)。两组不良反应发生率比较差异无统计学意义(P>0.05)。结论:小剂量罗红霉素能改善支气管哮喘患者肺通气功能,缓解气道高反应性,且安全性较好。     

甘草酸协同麻黄碱的平喘作用机制研究

目的：探讨甘草酸协同麻黄碱的平喘作用机制。方法：利用基于CHO细胞的β2肾上腺素受体（β2-AR）激动药活性评价体系,豚鼠离体气管收缩和组胺引喘的活体动物模型观察甘草酸和麻黄碱联用的协同平喘效果。结果：甘草酸自身不能引起离体气管平滑肌舒张,平喘效果也不显著,但与麻黄碱联用可以通过提高β2-AR的激动效果,明显增强平喘效果。结论：甘草酸通过调节β2-AR信号通路增强麻黄碱的作用效果,两者联用有良好的协同作用。     

β2-AR27位点基因多态性对气道高反应性的保护性作用研究

目的 探讨β2-AR 27位点基因多态性与哮喘的关系及其对气道高反应性的保护作用.方法 采用多聚酶链反应（PCR）-等位基因扩增法,对149例具有气道高反应性的咳嗽变异型哮喘患者进行β2-AR 27位点基因多态性分析检测,同时追踪2年,观察其发展成典型哮喘的比率,并与90名健康对照者进行比较.结果 （1）中国南方汉族人群β2-AR 27位点基因多态性分布以杂合子所占比例较高（57%）,突变型纯合子比率较小（20%）;（2）哮喘组β2-AR 27位点谷氨酸/谷氨酸基因型频率,明显低于健康对照组（9%VS20%）,OR为0.4（P＜0.05）,95%CI为（0.2～0.9）,谷氨酸等位基因频率与对照组差异无统计学意义（P＞0.05）;（3）β2-AR 27位点基因多态性在典型哮喘组谷氨酸/谷氨酸基因型分布频率明显低于哮喘稳定组（P＜0.05）.结论 中国南方汉族人群中27位点基因多态性与哮喘关联,Glu27可能具有气道保护作用.     

注射用甘草酸单铵S细菌内毒素检测方法的研究

目的建立复方甘草酸单铵S的细菌内毒素检查方法。方法参照《中国药典》2005年版(二部)细菌内毒素检查法进行试验。结果样品浓度为0.07mg.mL-1,不干扰细菌内毒素试验。结论该产品采用细菌内毒素检查是可行的。     

观察复方甘草酸单铵联合抗组织胺药物治疗慢性荨麻疹的效果

目的:探讨对慢性荨麻疹患者采用复方甘草酸苷单铵联合抗组胺药物进行治疗后的效果.方法:选取在我院进行治疗的慢性荨麻疹患者82例,就诊时间位于2018年12月-2020年6月,按照治疗方案的不同将其分为两组,选取对照组41例患者采用盐酸西替利嗪片进行治疗与选取观察组41例患者采用复方甘草酸单铵与枸地氯雷他定进行治疗,就两组...     

吸入呋塞米对支气管哮喘病人气道反应性的影响

目的 :探讨吸入呋塞米对支气管哮喘 (哮喘 )病人气道反应性的影响。方法 :缓解期哮喘病人4 0例 ,随机分为A ,B 2组 ,每组各 2 0例。试验分 2次隔日交叉吸入 0 .9%氯化钠注射液 4mL或呋塞米 4 0mg后予组胺吸入激发试验。结果 :2组病人吸入 0 .9%氯化钠注射液后的组胺PC2 0 FEV1差异无显著意义 (P >0 .0 5) ;吸入呋塞米后的组胺PC2 0 FEV1差异亦无显著意义 (P >0 .0 5) ;但 2组病人吸入呋塞米后的组胺PC2 0 FEV1均显著高于其吸入0 .9%氯化钠注射液后的组胺PC2 0 FEV1(均P <0 .0 5)。结论 :吸入呋塞米可抑制哮喘病人的气道高反应性。     

观察复方甘草酸苷、甘草酸二铵、异甘草酸镁3种甘草酸制剂治疗病毒性肝炎合并高胆红素血症的临床疗效

目的分析研究复方甘草酸苷、甘草酸二铵、异甘草酸镁3种甘草酸制剂治疗病毒性肝炎合并高胆红素血症的临床疗效。方法在本院2015年4月至2017年4月间收治的病毒性肝炎合并高胆红素血症患者中选择90例作为此次研究对象,将90例患者随机分为3组,1组为A组采取甘草酸二铵治疗,1组为B组采取复方甘草酸苷治疗,1组为C组采取异甘草酸镁进行治疗,各30例。结果 C组患者的肝功能指标较之A组及B组改善效果更为显著,与A组比较,B组的改善效果更佳(P<0.05)。对比临床治疗效果,提示C组最高,B组其次,A组最低(P<0.05)。结论 3种甘草酸制剂中异甘草酸镁治疗病毒性肝炎合并高胆红素血症的效果最为理想,临床可优先选择该制剂进行治疗。     

米帕林对β－肾上腺素能受体的作用

米帕林对β－肾上腺素能受体的作用邢成，季少平，王鲁明，吕宝璋（北京军事医学科学院基础医学研究所，北京１００８５０）米帕林（ｍｅｐａｃｒｉｎｅ，Ｍｅｐ）是磷脂酶Ａ，及磷脂酶Ｃ的抑制剂，也是一种膜稳定剂［１］．我们曾证实它在磷脂代谢和对β－肾上腺素能受体...     

COMBINED BRONCHODILATOR PROTECTION AGAINST HISTAMINE-INDUCED BRONCHOCONSTRICTION IN MAN

Sixteen stable asthmatics had the protective effects of inhaled fenoterol (200 micrograms) and inhaled ipratropium bromide (60 micrograms) against standardized histamine inhalation tests at 1 h examined in a randomized double blind fashion. There was no significant difference in the baseline forced expired volume in 1 s (FEV1) for the two study days (P greater than 0.05). There was an increase in FEV1 at 1 h on the fenoterol and ipratropium day compared with the fenoterol day (0.26 versus 0.17 l; P less than 0.05). The geometric mean provocative concentration of histamine to cause a 20% fall in FEV1 (PC20) was 6.31 mg/ml after fenoterol and 8.51 mg/ml after fenoterol and ipratropium (P = 0.038). There was no significant relationship between bronchodilator effect of the bronchodilators and the increase in PC20 from pre-study values, r = 0.307 (P = 0.25) for fenoterol alone and r = 0.195 (P = 0.47) for fenoterol and ipratropium. The relationship between pre-study histamine responsiveness and the increase in PC20 caused by the bronchodilators just failed to reach statistical significance, r = -0.441 (P = 0.09) for fenoterol alone and r = -0.47 (P = 0.06) for fenoterol and ipratropium. The study has shown a greater right shift of histamine responsiveness for combined inhaled fenoterol and ipratropium compared with inhaled fenoterol alone in this group of asthmatics.     

Airborne fine particulate matter causes murine bronchial hyperreactivity via MAPK pathway‐mediated M3 muscarinic receptor upregulation

Regarding the human health effects, airborne fine particulate matter 2.5 (PM_2.5) is an important environmental risk factor. However, the underlying molecular mechanisms are largely unknown. The present study examined the hypothesis that PM_2.5 causes bronchial hyperreactivity by upregulated muscarinic receptors via the mitogen‐activated protein kinase (MAPK) pathway. The isolated rat bronchi segments were cultured with different concentration of PM_2.5 for different time. The contractile response of the bronchi segments were recorded by a sensitive myograph. The mRNA and protein expression levels of M₃ muscarinic receptors were studied by quantitative real‐time PCR and immunohistochemistry, respectively. The muscarinic receptors agonist, carbachol induced a remarkable contractile response on fresh and DMSO cultured bronchial segments. Compared with the fresh or DMSO culture groups, 1.0 µg/mL of PM_2.5 cultured for 24 h significantly enhanced muscarinic receptor‐mediated contractile responses in bronchi with a markedly increased maximal contraction. In addition, the expression levels of mRNA and protein for M₃ muscarinic receptors in bronchi of PM_2.5 group were higher than that of fresh or DMSO culture groups. SB203580 (p38 inhibitor) and U0126 (MEK1/2 inhibitor) significantly inhibited the PM_2.5‐induced enhanced contraction and increased mRNA and protein expression of muscarinic receptors. However, JNK inhibitor SP600125 had no effect on PM_2.5‐induced muscarinic receptor upregulation and bronchial hyperreactivity. In conclusion, airborne PM_2.5 upregulates muscarinic receptors, which causes subsequently bronchial hyperreactivity shown as enhanced contractility in bronchi. This process may be mediated by p38 and MEK1/2 MAPK pathways. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 371–381, 2017.     

降气平喘中药对哮喘患者可溶性IL-2受体表达及气道高反应性的影响

目的：观察降气平喘中药对哮喘患者可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）表达及气道高反应性的影响。方法：６０例缓解期哮喘患者分为中药组、强的松组、β２受体组,分别于服药前后抽血,采用双抗体夹心ＥＬＡＳＡ测定ｓＩＬ－２Ｒ,采用乙酰甲胆碱吸入法测定气道反应性。结果：中药组与强的松组ｓＩＬ－２Ｒ与气道高反应性明显降低,治疗前后有非常显著性差异（Ｐ〈０．０１）。两组治疗后相比无统计学意义（Ｐ〉０．０５）。     

Study of the interaction of glutamatergic and nitrergic signalling in conditions of the experimental airways hyperreactivity

BackgroundGlutamatergic and nitrergic system participate in the control of respiratory system functions. It is only little information regarding a possible interaction of both systems in the airways hyperractivity. We investigated the effect of agents modulating the activity of these systems on the experimental ovalbumin-induced airways hyperreactivity as well as on the changes of exhaled nitric oxide (eNO) levels.MethodsWe used the agonists of NMDA receptors – N-methyl-D-aspartic acid (NMDA) and monosodium glutamate (MSG), selective competitive antagonist (DL-2-amino-5-phosphonovaleric acid – AP-5) and selective non-competitive antagonist (dizocilpine – MK-801) of these receptors. We used also non-specific inhibitor of NO synthases N^ω-nitro-L-arginine methyl ester (L-NAME). The airways responsiveness to histamine or acetylcholine was evaluated under in vitro conditions.ResultsNMDA administration caused the increase of tracheal smooth muscle response in ovalbumin-induced hyperreactivity to acetylcholine. The effect of MSG was less pronounced. MK-801 as well as AP-5 provoked the decrease of reactivity mainly to acetylcholine in tracheal smooth muscle. We recorded the changes in eNO levels. The activation of NMDA receptor with NMDA or MSG increased eNO levels. The inhibition of NO synthase with L-NAME caused the fall of eNO levels. MK-801 shows (within the group) the more expressive effect in the eNO levels during sensitization than AP-5 group.ConclusionThe results confirm the possibility of NMDA receptors participation in the experimental airways hyperreactivity.     

老年大鼠心脏肾上腺素受体亚型的改变(英文)

目的:研究老年心脏肾上腺素受体亚型的改变.方法:制备3月龄与25月龄Wistar大鼠心脏膜标本,分别采用~(125)I-BE2254与~(125)I-Pindold作放射配基结合分析,测定α_1与β-肾上腺素受体.结果:老年大鼠心脏的α_1与β-肾上腺受体密度分别由年轻大鼠的119±4与45.9±1.9pmol/g下降至70±6与36.4±1.6 pmol/g(P<0.01),α_1-AR降低的幅度大于β-AR.此外α_(1A)与α_(1B)亚型之比由年轻大鼠的39:61下降至26:74(P<0.05).结论:老年大鼠心脏肾上腺素受体减少,且不同亚型减少的程度不同.     

去甲乌药碱的药理作用与心脏β－AR关系的初步研究

附子有效成分去甲乌药碱（ＤＭＣ）的药理作用以及与肾上腺素能β受体（β－ＡＲ）的关系的研究表明，０．５ｍｇ·ｋｇ－１的ＤＭＣ可使正常小鼠心肌β－ＡＲ轻度上调，与异丙肾上腺素（ＩＳＯ）相比，ＤＭＣ能轻度激动ｃＡＭＰ，使其血浆含量升高，升高的峰值时间在１０ｍｉｎ左右。ＤＭＣ的最小激动量为０．５ｍｇ·ｋｇ－１，最大激动量为５ｍｇ·ｋｇ－１。ＤＭＣ对１２５Ｉ－ＰＩＮ的竞争抑制实验表明，在１×１０－６～１×１０－５ｍｏｌ·Ｌ－１时，ＤＭＣ可抑制１２５Ｉ－ＰＩＮ与β－ＡＲ结合，与心得安比较抑制浓度大４～５个数量级。与ＩＳＯ合并用药观察血浆ｃＡＭＰ浓度变化提示，０．５ｍｇ·ｋｇ－１ＤＭＣ与小剂量（０．１ｍｇ·ｋｇ－１）和较大剂量（１ｍｇ·ｋｇ－１）的ＩＳＯ合用时，既无协同作用，也未见拮抗作用。     

Non-bronchodilating mechanisms of tiotropium prevent airway hyperreactivity in a guinea-pig model of allergic asthma

BACKGROUND AND PURPOSE

Asthma is characterized by reversible bronchoconstriction and airway hyperreactivity. Although M₃ muscarinic receptors mediate bronchoconstriction, non-selective muscarinic receptor antagonists are not currently recommended for chronic control of asthma. We tested whether selective blockade of M₃ receptors, at the time of antigen challenge, blocks subsequent development of airway hyperreactivity in antigen-challenged guinea-pigs.

EXPERIMENTAL APPROACH

Ovalbumin-sensitized guinea-pigs were pretreated with 1 µg·kg⁻¹ of a kinetically selective M₃ receptor antagonist, tiotropium, or 1 mg·kg⁻¹ of a non-selective muscarinic receptor antagonist, atropine, and challenged with inhaled ovalbumin. Animals were anaesthetized, paralyzed, ventilated and vagotomized 24 h later. We measured vagally mediated bronchoconstriction and i.v. ACh-induced bronchoconstriction.

KEY RESULTS

Electrical stimulation of both vagus nerves induced frequency-dependent bronchoconstriction in sensitized animals that was significantly increased after antigen challenge. Antigen-induced hyperreactivity was completely blocked by tiotropium pretreatment but only partially blocked by atropine pretreatment. Surprisingly, although tiotropium blocked bronchoconstriction induced by i.v. ACh, it did not inhibit vagally-induced bronchoconstriction in sensitized controls, suggesting that tiotropium does not block hyperreactivity by blocking receptors for vagally released ACh. Rather, tiotropium may have worked through an anti-inflammatory mechanism, since it inhibited eosinophil accumulation in the lungs and around nerves.

CONCLUSIONS AND IMPLICATIONS

These data confirm that testing M₃ receptor blockade with exogenous ACh does not predict vagal blockade. Our data also suggest that selective blockade of M₃ receptors may be effective in asthma via mechanisms that are separate from inhibition of bronchoconstriction.     

Effect of histamine on human bronchial arteries in vitro

Summary Histamine caused a concentration-dependent relaxation at lower concentrations (1 pmol/1–1 mol/l) and contraction at higher concentrations (0.01–1 mmol/l) of isolated precontracted human bronchial arteries. In the vessels at resting tension only concentration-dependent contraction was evoked by histamine (0.01–1 mmol/l). Both the contractile and relaxant responses were significantly antagonised by mepyramine (1 gmol/l), with an estimated pK_B value of 8.4, but not by cimetidine (100 mol/l). Our results indicate that histamine induces biphasic effects on human bronchial arteries via H₁-re-ceptors. Send offprint requests to P. J. Barnes at the above address     

丙泊酚静脉注射对大鼠心室功能及心肌β肾上腺素受体的影响

目的研究丙泊酚静脉注射对大鼠心室功能及心肌β肾上腺素受体密度及亲和力的影响。方法24只清洁级雄性Wistar大鼠随机分为3组,每组8只:对照组、丙泊酚5 mg·kg~(-1)组及丙泊酚10 mg·kg~(-1)组。记录丙泊酚给药前及给药后30 min内所有动物的心率(HR)、左室收缩压(LVSP)及左室内压力变化最大速率(+dp/dt_(max)、-dp/dt_(max)),并采用放免法测定给药后30 min时心肌β肾上腺素受体密度(B_(max))及亲和力(K_d)。结果(1)HR、LVSP、+dp/df_(max)及-dP/dt_(max)分别在丙泊酚5 mg·kg~(-1)静脉给药后9、5、30及9 min内明显低于给药前值;并在给药后9、7、7及9 min内分别明显低于对照组(P<0.05或0.01)。HR、LVSP、+dp/dt_(max)及-dp/df_(max)分别在丙泊酚10 mg·kg~(-1)静脉给药后25、5、30及8 min内明显低于给药前值;并在给药后8、7、7及8 min内分别明显低于对照组(P<0.05或0.01)。丙泊酚2组间比较无明显差异(P>0.05)。(2)丙泊酚5 mg·kg~(-1)组及10 mg·kg~(-1)组B_(max)明显高于对照组(P<0.01);丙泊酚10 mg·kg~(-1)组K_d值明显高于对照组及丙泊酚5 mg·kg~(-1)组(P<0.05);其余各组间比较无明显差异(P>0.05)。结论丙泊酚可引起给药后30 min内心室功能抑制,5 mg·kg~(-1)及10 mg·kg~(-1)上调给药后30 min心肌β肾上腺素受体密度。