中华结核和呼吸杂志
中華結覈和呼吸雜誌
중화결핵화호흡잡지
Chinese Journal of Tuberculosis and Respiratory Diseases
2009年
4期
282-286
,共5页
刘维佳%李万成%徐治波%冯玉麟
劉維佳%李萬成%徐治波%馮玉麟
류유가%리만성%서치파%풍옥린
丙烯醛%黏液%过氧化物酶体增殖物激活受体
丙烯醛%黏液%過氧化物酶體增殖物激活受體
병희철%점액%과양화물매체증식물격활수체
Acrolein%Mucus%Peroxisome proliferators-activated receptor
目的 探讨过氧化物酶体增殖物激活受体-γ(PPAR-γ)及其配体对气道黏液高分泌的作用及其机制.方法 应用随机数字表法将36只SD大鼠随机分为4组,其中生理盐水对照组(6只)雾化吸入生理盐水;罗格列酮对照组(6只)雾化吸入生理盐水,同时给予罗格列酮8 mg/kg灌胃;丙烯醛组(6只)雾化吸入丙烯醛3.0 mg/L,6 h/d,连续12 d;罗格列酮干预组根据不同剂量又分为低、中、高剂最组,每组各6只,在雾化吸入丙烯醛的同时分别给予2、4和8 mg/kg罗格列酮灌胃.采用HE染色及阿辛蓝-过碘酸雪夫染色法观察支气管肺组织的病理改变和气道黏液物质改变,应用实时荧光定量逆转录-PCR及免疫组织化学SP法检测黏蛋白5AC和PPAR-γ的表达水平.组间比较采用方差分析,两组比较采用q检验,相关性分析采用Pearson法.结果 丙烯醛组、生理盐水对照组及低、中、高剂量罗格列酮干预组气道黏液物质的相对着色而积分别为(60.2±9.3)%、(4.9±1.0)%、(53.3±8.5)%、(26.5±7.4)%和(12.5±3.7)%,组间比较差异有统计学意义(F=93.80,P＜0.01).黏蛋白5AC蛋白在丙烯醛组、生理盐水对照组及低、中、高剂量罗格列酮干预组表达的积分吸光度值分别为4339±453、1636±282、3996±346、3048±331和2376±343,组间比较差异有统计学意义(F=67.74,P＜0.01);PPAR-γ蛋白表达的积分吸光度值分别为1159±184、838±151、1272±189、1568±282和1872±270,组间比较差异有统计学意义(F=21.53,P＜0.01).丙烯醛组、生理盐水对照组及低、中、高剂量罗格列酮干预组黏蛋白5AC mRNA表达的相对拷贝数分别为35.3±10.0、2.2±0.7、30.5±10.2、18.6±5.3和10.8±2.6,组问比较差异有统计学意义(F=29.67,P＜0.01);PPAR-γ mRNA的相对拷贝数分别为7.8±1.9、2.0±0.6、9.8±2.8、18.6±5.3和31.6±8.9,组间比较差异有统计学意义(F=39.47,P＜0.01).丙烯醛组PPAR-γ蛋白水平与黏蛋白5AC mRNA表达呈负相关(r=-0.880,P＜0.01).结论 丙烯醛致气道黏液高分泌过程与PPAR-γ表达异常有关;PPAR-γ及其配体罗格列酮可以抑制丙烯醛诱导的气道黏液高分泌,其具体机制可能与下调黏蛋白5AC的表达有关.
目的 探討過氧化物酶體增殖物激活受體-γ(PPAR-γ)及其配體對氣道黏液高分泌的作用及其機製.方法 應用隨機數字錶法將36隻SD大鼠隨機分為4組,其中生理鹽水對照組(6隻)霧化吸入生理鹽水;囉格列酮對照組(6隻)霧化吸入生理鹽水,同時給予囉格列酮8 mg/kg灌胃;丙烯醛組(6隻)霧化吸入丙烯醛3.0 mg/L,6 h/d,連續12 d;囉格列酮榦預組根據不同劑量又分為低、中、高劑最組,每組各6隻,在霧化吸入丙烯醛的同時分彆給予2、4和8 mg/kg囉格列酮灌胃.採用HE染色及阿辛藍-過碘痠雪伕染色法觀察支氣管肺組織的病理改變和氣道黏液物質改變,應用實時熒光定量逆轉錄-PCR及免疫組織化學SP法檢測黏蛋白5AC和PPAR-γ的錶達水平.組間比較採用方差分析,兩組比較採用q檢驗,相關性分析採用Pearson法.結果 丙烯醛組、生理鹽水對照組及低、中、高劑量囉格列酮榦預組氣道黏液物質的相對著色而積分彆為(60.2±9.3)%、(4.9±1.0)%、(53.3±8.5)%、(26.5±7.4)%和(12.5±3.7)%,組間比較差異有統計學意義(F=93.80,P＜0.01).黏蛋白5AC蛋白在丙烯醛組、生理鹽水對照組及低、中、高劑量囉格列酮榦預組錶達的積分吸光度值分彆為4339±453、1636±282、3996±346、3048±331和2376±343,組間比較差異有統計學意義(F=67.74,P＜0.01);PPAR-γ蛋白錶達的積分吸光度值分彆為1159±184、838±151、1272±189、1568±282和1872±270,組間比較差異有統計學意義(F=21.53,P＜0.01).丙烯醛組、生理鹽水對照組及低、中、高劑量囉格列酮榦預組黏蛋白5AC mRNA錶達的相對拷貝數分彆為35.3±10.0、2.2±0.7、30.5±10.2、18.6±5.3和10.8±2.6,組問比較差異有統計學意義(F=29.67,P＜0.01);PPAR-γ mRNA的相對拷貝數分彆為7.8±1.9、2.0±0.6、9.8±2.8、18.6±5.3和31.6±8.9,組間比較差異有統計學意義(F=39.47,P＜0.01).丙烯醛組PPAR-γ蛋白水平與黏蛋白5AC mRNA錶達呈負相關(r=-0.880,P＜0.01).結論 丙烯醛緻氣道黏液高分泌過程與PPAR-γ錶達異常有關;PPAR-γ及其配體囉格列酮可以抑製丙烯醛誘導的氣道黏液高分泌,其具體機製可能與下調黏蛋白5AC的錶達有關.
목적 탐토과양화물매체증식물격활수체-γ(PPAR-γ)급기배체대기도점액고분비적작용급기궤제.방법 응용수궤수자표법장36지SD대서수궤분위4조,기중생리염수대조조(6지)무화흡입생리염수;라격렬동대조조(6지)무화흡입생리염수,동시급여라격렬동8 mg/kg관위;병희철조(6지)무화흡입병희철3.0 mg/L,6 h/d,련속12 d;라격렬동간예조근거불동제량우분위저、중、고제최조,매조각6지,재무화흡입병희철적동시분별급여2、4화8 mg/kg라격렬동관위.채용HE염색급아신람-과전산설부염색법관찰지기관폐조직적병리개변화기도점액물질개변,응용실시형광정량역전록-PCR급면역조직화학SP법검측점단백5AC화PPAR-γ적표체수평.조간비교채용방차분석,량조비교채용q검험,상관성분석채용Pearson법.결과 병희철조、생리염수대조조급저、중、고제량라격렬동간예조기도점액물질적상대착색이적분별위(60.2±9.3)%、(4.9±1.0)%、(53.3±8.5)%、(26.5±7.4)%화(12.5±3.7)%,조간비교차이유통계학의의(F=93.80,P＜0.01).점단백5AC단백재병희철조、생리염수대조조급저、중、고제량라격렬동간예조표체적적분흡광도치분별위4339±453、1636±282、3996±346、3048±331화2376±343,조간비교차이유통계학의의(F=67.74,P＜0.01);PPAR-γ단백표체적적분흡광도치분별위1159±184、838±151、1272±189、1568±282화1872±270,조간비교차이유통계학의의(F=21.53,P＜0.01).병희철조、생리염수대조조급저、중、고제량라격렬동간예조점단백5AC mRNA표체적상대고패수분별위35.3±10.0、2.2±0.7、30.5±10.2、18.6±5.3화10.8±2.6,조문비교차이유통계학의의(F=29.67,P＜0.01);PPAR-γ mRNA적상대고패수분별위7.8±1.9、2.0±0.6、9.8±2.8、18.6±5.3화31.6±8.9,조간비교차이유통계학의의(F=39.47,P＜0.01).병희철조PPAR-γ단백수평여점단백5AC mRNA표체정부상관(r=-0.880,P＜0.01).결론 병희철치기도점액고분비과정여PPAR-γ표체이상유관;PPAR-γ급기배체라격렬동가이억제병희철유도적기도점액고분비,기구체궤제가능여하조점단백5AC적표체유관.
Objective To explore the effect and the molecular mechanisms of peroxisome proliferators activated receptor gamma(PPAR-γ)and its ligand on airway mucus hypersecretion.Methods Thirty-six Sprague-Dawley rats were randomized into the following groups:(1)Rats in the saline control group(n=6)received normal saline inhalation;(2)Rats in the rosiglitazone control group(n=6)received inhaled saline and oral rosiglitazone 8 mg/kg simultaneously;(3)Rats in the acrolein group(n=6)received inhaled acroline 3.0 mg/L,6 h/day,for 12 days;(4)Rats in the rosiglitazone intervention group(n=18)received inhaled acrolein and oral rosiglitazone 2 mg/kg,4 mg/kg,8 mg/kg,respectively,as the low dose,the moderate dose and the high dose intervention groups(n=6 each).The lung tissue sections were stained with HE for histopathological examination.The changes of airway mucus were examined with AB-PAS.Expressions of MUC5AC and PPAR-γ protein in the bronchial epithelium were detected by immunohistochemistry.The expression of mRNA was measured with real time RT-PCR.The data were analyzed with SPSS 10.0 software.Variables were compared with One-Way ANOVA and q test.The correlations between variables were analyzed using Pearson's correlation coefficient.Results The levels of airway mucus were(60.2±9.3)%,(4.9±1.0)%,(53.3±8.5)%,(26.5±7.4)%,(12.5±3.7)% respectively in the acrolein group,the saline control group,the low dose rosiglitazone intervention group,the moderate dose rosiglitazone intervention group,and the high dose rosiglitazone intervention group,the difference being significant among groups(F=93.80,P＜0.01).The protein expressions of MUC5AC in the bronchial epithelium examined by immunohistochemistry were 4339±453,1636±282,3996±346,3048±331,2376±343 respectively in the acrolein group,the saline control group,the low dose msiglitazone intervention group,the moderate dose rosiglitazone intervention group,and the high dose rosiglitazone intervention group,the difference being significant among groups(F=67.74,P＜0.01).The protein expressions of PPAR-γ were 1159±184,838±151,1272±189,1568±282,1872±270 respectively in the acrolein group,the saline control group,the low dose rosiglitazone intervention group,the moderate dose rosiglitazone intervention group,and the high dose rosiglitazone intervention group,the difference being significant among groups(F=21.53,P＜0.01).The mRNA expressions of MUC5AC(the relative copies)were 35.3±10.0,2.2±0.7,30.5±10.2,18.6±5.3,10.8±2.6 respectively in the acrolein group,the saline control group,the low dose rosiglitazone intervention group,the moderate dose rosiglitazone intervention group,and the high dose rosiglitazone intervention group,the difference being significant among groups(F=29.67,P＜0.01).The mRNA expressions of PPAR-γ(the relative copies)were 7.8±1.9.2.0±0.6.9.8±2.8,18.6±5.3,31.6±8.9 in the acrolein group,the saline control group,the low dose rosiglitazone intervention group,the moderate dose rosiglitazone intervention group,and the high dose rosiglitazone intervention group,the difference being significant among groups(F=39.47,P＜0.01).The expression of MUC5AC mRNA was negatively correlated with the protein expression of PPAR-γ in the acrolein group(r=-0.880,P＜0.01).Conclusions PPAR-γ was involved in airway mucus hypersecretion induced by acrolein.PPAR-γ and its ligand rosiglitazone inhibited acrolein-induced airway mucus hypersecretion,possibly through downregulation of MUC5AC.
