布地奈德对哮喘大鼠内源性H_2S、CSE、CBS体系的调节机制

Regulative mechanism of budesonide on endogenous hydrogen sulfide,cystathionine-γ-lyase and cystathionine-β-synthase system in asthmatic rats

目的观察布地奈德对哮喘大鼠血浆硫化氢(H2S)含量和胱硫醚-γ-裂解酶(CSE)、胱硫醚-β-合成酶(CBS)mRNA的表达,探讨内源性H2S、CSE、CBS体系在哮喘发病机制中的作用。方法 Sprague-Dawley大鼠30只随机分成对照组、哮喘组、布地奈德组,每组10只。用鸡卵白蛋白(OVA)致敏与激发建立大鼠哮喘模型。分光光度法测定血浆H2S的含量,RT-PCR法测定肺组织CSE、CBSmRNA的表达水平。结果哮喘组血浆H2S的含量(61±16μmol/L)显著低于对照组(84±15μmol/L)(P<0.01),布地奈德组(71±14μmol/L)与哮喘组和对照组相比差异无统计学意义(P>0.05)。哮喘组肺组织CSEmRNA和CBSmRNA的表达水平显著低于对照组(P<0.01),布地奈德组CSEmRNA和CBSmRNA表达显著低于对照组但高于哮喘组(均P<0.01)。相关性分析结果显示血浆H2S含量和支气管肺泡灌洗液(BALF)中炎症细胞总数表达呈显著负相关(n=30,r=-0.549,P<0.01)。结论哮喘大鼠H2S、CSE、CBS的表达下降,它们的表达下降可能促进了炎症细胞在气道中的聚集,布地奈德改善哮喘炎症的机制可能部分通过内源性H2S、CSE、CBS体系起作用。

Objective To investigate plasma hydrogen sulfide（H2S）levels and cystathionine-γ-lyase（CSE）and cystathionine-β-synthase（CBS）mRNA expression in the lung tissues in asthmatic rats and to explore the roles of endogenous H2S,CSE and CBS system in the pathogenesis of asthma.Methods Thirty male Sprague-Dawley rats（age 5 to 7 weeks）were randomly divided into three groups：control,asthma and budesonide treatment（n=10 each）.The asthma model was established by ovalbumin（OVA）sensitization and challenge.The budesonide treatment group received inhaled budesonide before challenge.The contents of plasma H2S were measured by spectrophotometry.The levels of CSE and CBS mRNA in the lung tissues were examined by reverse transcriptase polymerase chain reaction（RT-PCR）.Results The contents of plasma H2S in the asthma group（61±16 μmol/L）were significantly lower than those in the control group（84±15 μmol/L）（P〈0.01）.The contents of plasma H2S in the budesonide treatment group（71±14 μmol/L）were not statistically different from those in the control and asthma groups.CSE mRNA and CBE mRNA expression in the asthma group were significantly lower than those in the control group（P〈0.01）.The budesonide treatment group had a decreased CSE mRNA expression and CBE mRNA expression compared with the control group,but had significantly increased CSE and CBE mRNA expression compared with the asthma group（P〈0.01）.There was a significantly negative correlation between H2S contents in plasma and total inflammatory cells in bronchoalveolar lavage fluid（n=30,r=-0.549,P〈0.01）.Conclusions Plasma H2S levels and CSE and CBS expression in the lung decrease in asthmatic rats,which possibly promotes inflammatory cell aggregation to the airway.Budesonide may alleviate airway inflammation in asthmatic rats possibly through the system of endogenous H2S,CSE and CBS.