硫化氢供体对急性支气管哮喘大鼠尾加压素Ⅱ表达的影响

目的: 探讨应用外源性硫氢化钠(NaHS,H₂S供体)处理对卵白蛋白(OVA)诱导的大鼠急性支气管哮喘(简称哮喘)模型大鼠尾加压素Ⅱ(U-Ⅱ)表达的影响。方法: 24只SPF级健康SD大鼠随机数字表法分为对照组、哮喘组和NaHS干预组,每组8只。致敏后28 d测定所有大鼠肺功能。观察大鼠支气管周围病理炎症细胞浸润程度并进行评分;采用放射免疫法分别测定大鼠血浆、肺组织及肺泡灌洗液的U-Ⅱ含量。 结果: (1)对照组、哮喘组和NaHS干预组大鼠最大呼气峰流速(PEF)分别为(6.5±0.1)L/s、(2.9±0.7)L/s及(5.7±0.5)L/s, 3组间差异显著(F=112.129,P< 0.01);(2)血浆U-Ⅱ含量分别为(45.3±18.1)ng/L、(61.5±27.2)ng/L、(47.3±11.8)ng/L,3组间无显著差异(F= 1.546, P> 0.05);(3)大鼠肺组织及肺泡灌洗液U-Ⅱ含量对照组分别为(16.6±3.4)ng/L及(26.3±7.8)ng/L,哮喘组分别为(43.8±2.0)ng/L及(58.0±12.3)ng/L,NaHS干预组分别为(14.0±1.9)ng/L及(20.2±6.7)ng/L,3组间差异显著(F=337.68、F=38.433, 均P< 0.01); (4)光镜下支气管周围炎症细胞浸润程度评分 ,对照组为1 (0-1)分,哮喘组为3 (2-4)分,NaHS干预组1(1-2)分,3组间差异显著(H=16.925, P< 0.01);(5)大鼠肺组织及肺泡灌洗液U-Ⅱ含量与光镜下支气管周围炎症细胞浸润程度评分均呈正相关(r=0.746、r=0.714, P< 0.01),与PEF均呈负相关(r=-0.911、r=-0.767,均P<0.01)。结论: 哮喘急性发作时气道U-Ⅱ分泌增加,U-Ⅱ可能以旁/自分泌的方式参与哮喘的发病;而H₂S外源性供给可通过抑制U-Ⅱ合成/分泌,减轻哮喘急性发作时的气道炎症,对哮喘急性发病起到防治作用。

Effects of hydrogen sulfide on expression of urotensin II in acute asthmatic rats

AIM: To explore the effects of exogenously applied hydrogen sulfide (H₂S)on expression of urotensin II (U-II)in rats with ovalbumin-induced acute asthma. METHODS: Twenty-four male SD rats were randomly divided into control group, asthma group and NaHS treatment group (all n=8). At the 28th day after ovalbumin sensitization, the pulmonary function was measured. The pathological changes in the lung tissues were observed. The contents of U-II in plasma, lung tissues and bronchoalveolar lavage fluid (BALF)was also detected.RESULTS: The peak expiratory flow (PEF) was(6.5±0.1)L/s,(2.9±0.7)L/s and(5.7±0.5)L/s in control group, asthma group and NaHS treatment group, respectively. No statistical difference of the plasma U-II levels was observed among the three groups. In asthma group, the content of U-II in lung tissues was(43.8±2.0)ng/L and that in BALF was(58.0±12.3)ng/L, both of which were significantly higher than those in control group . In NaHS treatment group, the content of U-II in lung tissues was(14.0±1.9)ng/L and that in BALF was(20.2±6.7)ng/L, both of which were significantly lower than those in asthma grou p (F=337.68 and F=38.433, respectiuely, both P<0.01). The pathological score of the lung tissues in asthma group was 3(2-4), significantly higher than that in control group and NaHS treatment group . The positive correlations between the contents of U-II in lung tissues or BALF and the pathological scores were observed (r=0.746,r=0.714, respectively, both P<0.01). Significantly negative correlations between the contents of U-II in lung tissues or BALF and PEF were also found (r=-0.911 and r=-0.767, respectively, both P<0.01).CONCLUSION: U-II, a mediator acting via the way of paracrine or autocrine, may play a role in the pathogenesis of asthma in this animal model. The exogenous application of H₂S may play a regulatory role in asthma through inhibiting U-II to attenuate the inflammatory responses in asthma and exert protective effect on the pulmonary functions.