国际呼吸杂志
國際呼吸雜誌
국제호흡잡지
INTERNATIONAL JOURNAL OF RESPIRATION
2011年
9期
651-655
,共5页
哮喘%虫草%气道重塑%转化生长因子β1%腺甘A2a受体
哮喘%蟲草%氣道重塑%轉化生長因子β1%腺甘A2a受體
효천%충초%기도중소%전화생장인자β1%선감A2a수체
Asthma%Cordycepin%Airway remodeling%Transforming growth factor-β1%A2aadenosine receptor
目的 对虫草活力素(简称虫草)在大鼠支气管哮喘(简称哮喘)模型气道重塑中的作用及相关机制进行初步探讨.方法 50只Wister大鼠[6～8周龄,(200±20)g],随机数字表法分为阴性对照组(A)、慢性哮喘单纯模型组(B)(卵清白蛋白系统致敏和反复激发)、慢性哮喘+虫草50 mg/kg治疗8周组(C)、慢性哮喘+布地奈德(BUD)8周治疗组(D)及慢性哮喘+BUD联合虫草8周治疗组(E).肺组织切片HE染色观察病理变化并检测气道管壁厚度,采用免疫组织化学法检测气道转化生长因子β1(TGF-β1)表达水平,应用逆转录PCR法检测肺组织A2a腺苷受体(A2aAR)mRNA表达.数据统计采用ANOVA检验进行组间分析,Mann-Whitney检验进行组内两两比较,Spearman等级相关分析.结果①HE染色显示所有药物干预组较单纯模型组炎症细胞浸润、平滑肌肥厚及黏膜肺组织水肿等炎症表现明显减轻,以D和E组最为明显;②5组气道管壁厚度依次分别为(9.89±2.09)、(21.72±3.16)、(14.94±1.96)、(12.29±2.75)和(12.25±2.32)μm2/μm,F=31.37,P<0.000 1,所有药物干预组气道壁厚度均高于对照组(C组、D组和E组与A组比较后的P值分别为0.000 1,0.052 4、0.052 4).且低于单纯模型组(C组、D组和E组与B组比较后的P值均<0.000 1),差异有统计学意义,C组气道壁较D组和E组增厚,差异有统计学意义(P值分别为0.023 2和0.014 7);③5组TGF-β2表达强阳性率分别为(2.08±1.63)%、(29.37±5.08)%、(12.30±3.26)%、(10.78±3.35)%及(7.43±2.84)%,F=86.45,P<0.000 1,所有药物干预组TGF-β1蛋白表达均高于对照组(C组、D组和E组与A组比较后的P值均<0.000 1),且低于单纯模型组(C组、D组和E组与B组比较后的P值均<0.000 1),差异有统计学意义;E组较C组的蛋白表达有统计学意义下降(P=0.005 2);④5组肺组织A2aAR mRNA表达相对强度依次为(0.35±0.06)、(0.27±0.10)、(0.52±0.07)、(0.24±0.05)及(0.47±0.08),F=26.46,P<0.000 1,C组和E组A2aAR mRNA表达高于A组(P值分别为0.000 1及0.000 7)、B组(P值分别为0.000 2及0.000 3)和D组(P值均<0.000 1),差异有统计学意义.D组表达低于A组,差异有统汁学意义(P=0.000 3);⑤所有大鼠支气管壁厚度与气道TGF-β1蛋白表达存和正相关(r=0.80,P<0.01),而C组大鼠肺组织A2aAR mRNA表达和TGF-β1蛋白表达呈负相关(r=0.68,P=0.03).结论 虫草对哮喘模型的气道重塑具有一定的改善作用,其机制可能通过增加慢性哮喘模型大鼠肺组织A2aAR mRNA转录,抑制气道TGF-β1的生成,从而减轻气道重塑,且虫草与糖皮质激素联合应用对于降低TGF-β1的表达具有潜在协同作用.
目的 對蟲草活力素(簡稱蟲草)在大鼠支氣管哮喘(簡稱哮喘)模型氣道重塑中的作用及相關機製進行初步探討.方法 50隻Wister大鼠[6～8週齡,(200±20)g],隨機數字錶法分為陰性對照組(A)、慢性哮喘單純模型組(B)(卵清白蛋白繫統緻敏和反複激髮)、慢性哮喘+蟲草50 mg/kg治療8週組(C)、慢性哮喘+佈地奈德(BUD)8週治療組(D)及慢性哮喘+BUD聯閤蟲草8週治療組(E).肺組織切片HE染色觀察病理變化併檢測氣道管壁厚度,採用免疫組織化學法檢測氣道轉化生長因子β1(TGF-β1)錶達水平,應用逆轉錄PCR法檢測肺組織A2a腺苷受體(A2aAR)mRNA錶達.數據統計採用ANOVA檢驗進行組間分析,Mann-Whitney檢驗進行組內兩兩比較,Spearman等級相關分析.結果①HE染色顯示所有藥物榦預組較單純模型組炎癥細胞浸潤、平滑肌肥厚及黏膜肺組織水腫等炎癥錶現明顯減輕,以D和E組最為明顯;②5組氣道管壁厚度依次分彆為(9.89±2.09)、(21.72±3.16)、(14.94±1.96)、(12.29±2.75)和(12.25±2.32)μm2/μm,F=31.37,P<0.000 1,所有藥物榦預組氣道壁厚度均高于對照組(C組、D組和E組與A組比較後的P值分彆為0.000 1,0.052 4、0.052 4).且低于單純模型組(C組、D組和E組與B組比較後的P值均<0.000 1),差異有統計學意義,C組氣道壁較D組和E組增厚,差異有統計學意義(P值分彆為0.023 2和0.014 7);③5組TGF-β2錶達彊暘性率分彆為(2.08±1.63)%、(29.37±5.08)%、(12.30±3.26)%、(10.78±3.35)%及(7.43±2.84)%,F=86.45,P<0.000 1,所有藥物榦預組TGF-β1蛋白錶達均高于對照組(C組、D組和E組與A組比較後的P值均<0.000 1),且低于單純模型組(C組、D組和E組與B組比較後的P值均<0.000 1),差異有統計學意義;E組較C組的蛋白錶達有統計學意義下降(P=0.005 2);④5組肺組織A2aAR mRNA錶達相對彊度依次為(0.35±0.06)、(0.27±0.10)、(0.52±0.07)、(0.24±0.05)及(0.47±0.08),F=26.46,P<0.000 1,C組和E組A2aAR mRNA錶達高于A組(P值分彆為0.000 1及0.000 7)、B組(P值分彆為0.000 2及0.000 3)和D組(P值均<0.000 1),差異有統計學意義.D組錶達低于A組,差異有統汁學意義(P=0.000 3);⑤所有大鼠支氣管壁厚度與氣道TGF-β1蛋白錶達存和正相關(r=0.80,P<0.01),而C組大鼠肺組織A2aAR mRNA錶達和TGF-β1蛋白錶達呈負相關(r=0.68,P=0.03).結論 蟲草對哮喘模型的氣道重塑具有一定的改善作用,其機製可能通過增加慢性哮喘模型大鼠肺組織A2aAR mRNA轉錄,抑製氣道TGF-β1的生成,從而減輕氣道重塑,且蟲草與糖皮質激素聯閤應用對于降低TGF-β1的錶達具有潛在協同作用.
목적 대충초활력소(간칭충초)재대서지기관효천(간칭효천)모형기도중소중적작용급상관궤제진행초보탐토.방법 50지Wister대서[6～8주령,(200±20)g],수궤수자표법분위음성대조조(A)、만성효천단순모형조(B)(란청백단백계통치민화반복격발)、만성효천+충초50 mg/kg치료8주조(C)、만성효천+포지내덕(BUD)8주치료조(D)급만성효천+BUD연합충초8주치료조(E).폐조직절편HE염색관찰병리변화병검측기도관벽후도,채용면역조직화학법검측기도전화생장인자β1(TGF-β1)표체수평,응용역전록PCR법검측폐조직A2a선감수체(A2aAR)mRNA표체.수거통계채용ANOVA검험진행조간분석,Mann-Whitney검험진행조내량량비교,Spearman등급상관분석.결과①HE염색현시소유약물간예조교단순모형조염증세포침윤、평활기비후급점막폐조직수종등염증표현명현감경,이D화E조최위명현;②5조기도관벽후도의차분별위(9.89±2.09)、(21.72±3.16)、(14.94±1.96)、(12.29±2.75)화(12.25±2.32)μm2/μm,F=31.37,P<0.000 1,소유약물간예조기도벽후도균고우대조조(C조、D조화E조여A조비교후적P치분별위0.000 1,0.052 4、0.052 4).차저우단순모형조(C조、D조화E조여B조비교후적P치균<0.000 1),차이유통계학의의,C조기도벽교D조화E조증후,차이유통계학의의(P치분별위0.023 2화0.014 7);③5조TGF-β2표체강양성솔분별위(2.08±1.63)%、(29.37±5.08)%、(12.30±3.26)%、(10.78±3.35)%급(7.43±2.84)%,F=86.45,P<0.000 1,소유약물간예조TGF-β1단백표체균고우대조조(C조、D조화E조여A조비교후적P치균<0.000 1),차저우단순모형조(C조、D조화E조여B조비교후적P치균<0.000 1),차이유통계학의의;E조교C조적단백표체유통계학의의하강(P=0.005 2);④5조폐조직A2aAR mRNA표체상대강도의차위(0.35±0.06)、(0.27±0.10)、(0.52±0.07)、(0.24±0.05)급(0.47±0.08),F=26.46,P<0.000 1,C조화E조A2aAR mRNA표체고우A조(P치분별위0.000 1급0.000 7)、B조(P치분별위0.000 2급0.000 3)화D조(P치균<0.000 1),차이유통계학의의.D조표체저우A조,차이유통즙학의의(P=0.000 3);⑤소유대서지기관벽후도여기도TGF-β1단백표체존화정상관(r=0.80,P<0.01),이C조대서폐조직A2aAR mRNA표체화TGF-β1단백표체정부상관(r=0.68,P=0.03).결론 충초대효천모형적기도중소구유일정적개선작용,기궤제가능통과증가만성효천모형대서폐조직A2aAR mRNA전록,억제기도TGF-β1적생성,종이감경기도중소,차충초여당피질격소연합응용대우강저TGF-β1적표체구유잠재협동작용.
Objective To investigate the potential suppression role of cordycepin in airway remodeling by observing the expression of transforming growth factor-β1 (TGF-β1 ) and A2a adenosine receptor (A2aAR) on a rat model of chronic bronchial asthma (asthma). Methods 50 rats were randomized into control group (A), asthma group (B), 50 mg/kg cordycepin treatment group (C),budesonide (BUD) treatment group (D) and combination treatment group (BUD + cordycepin 50 mg/kg) (E). After 8 weeks therapy on ovalbumin challenged asthma model, histologic examination were performed to observe the general pathologic alteration and analyze the thickness of airway wall. The protein expressions of TGF-β1 were calculated by immunohistochemistry, and the transcriptions of A2aAR mRNA in the lung tissues were measured by reverse transcriptase-polymerase chain reaction (RT-PCR).Data were evaluated using One-way ANOVA followed by Turkey's test and Mann-Whitney test. Results inflammatory ceils infiltration, heavier smooth muscle hypertrophy and mucous membrane hyperemia in (14.94±1.96),(12.29±2.75) and (12.25±2.32) μm2/μm respectively, F=31.37, P<0.000 1,airway thickness in group C, D and E were all significantly higher than group A ( P =0. 000 1,0. 052 4and 0.052 4 respectively), and lower than group B ( P < 0. 000 1). Airway in group C also showed TGF-β1, in eaehgroupwas (2. 08±1. 63) %,(29.37±5.08) %,(12.30±3.26)%,(10.78±3.35)and (7.43 ±2.84) % respectivcly, F= 86.45, P < 0. 000 1, protein expressions in group C, D and E were all higher than group A ( P <0. 000 1 ,<0. 000 1 and =0. 000 1 respectively) ,and lower than group B significantly ( P <0. 000 1), expression in group E also decreased remarkably than group C ( P=(0.52± 0. 07), (0.24 ±0.05 ) and (0.47 ± 0.08 ), respectively, F = 26.46, P < 0. 000 1. Compared to Group A, B and D, the levels of A2aAR mRNA in group C and E were significantly higher( P <0. 001),levels of TGF-β1 were positively correlated with airway thickness in all rats ( r =0. 80, P <0.01) ,while negative correlation were detected with thranseription of A2aAR in group C ( r =-0.68, P =0. 03).Conclusions Cordycepin may potentially inhabit the airway remodeling of asthma by up regulating the thranscription of A2aAR mRNA and down regulating the synthesis of TGF-β1, and may have synergistic effect in inhibiting the synthesis of TGF-β1 with corticosteroid.
