CAJ | 학술논문

目的探讨罗格列酮早期干预对野百合碱诱导动脉型肺动脉高压大鼠肺血管病变的作用及机制.方法 32只SD大鼠随机分为对照组、模型组及罗格列酮高、低剂量干预组,每组8只.对照组大鼠皮下注射生理盐水后常规饲养,模型组及罗格列酮高、低剂量干预组大鼠皮下注射野百合碱60 mg/kg,注射当日起分别以生理盐水(1.5 ml/d)、罗格列酮(5 mg/kg及2.5 mg/kg)每日1次灌胃.21 d后测定各组大鼠肺动脉平均压(mPAP),取肺组织观察肺小动脉周围炎症评分,测定肺小动脉管壁中膜厚度占管壁外径百分比(WT％),酶联免疫吸附(ELISA)法测定肺组织匀浆白细胞分素6(IL-6)、肿瘤坏死因子α(TNF-α)和单核细胞趋化蛋白1(MCP-1)水平.结果罗格列酮高、低剂量干预组mPAP[ (27±4)、(28 ±4) mm Hg(1 mm Hg =0.133 kPa)]和WT％(13.1％±3.9％、16.7％±1.7％)较模型组[(37±5) mm Hg和45.5％±5.5％]明显低(P＜0.01),但仍高于对照组[(17±3)mm Hg和8.9％±2.3％](P＜0.05和P＜0.01)；罗格列酮高、低剂量干预组肺小动脉周围炎症评分、肺组织匀浆IL-6、TNF-α及MCP-1水平均明显低于模型组(均P＜0.01)；罗格列酮高剂量干预组各项指标较低剂量干预组有降低趋势(P＞0.05).结论罗格列酮早期应用可延缓野百合碱诱导的大鼠动脉型肺动脉高压形成及肺血管重构,该作用可能与其抗炎作用有关,其对肺血管的保护作用与剂量有关.
목적 탐토라격렬동조기간예대야백합감유도동맥형폐동맥고압대서폐혈관병변적작용급궤제.방법 32지SD대서수궤분위대조조、모형조급라격렬동고、저제량간예조,매조8지.대조조대서피하주사생리염수후상규사양,모형조급라격렬동고、저제량간예조대서피하주사야백합감60 mg/kg,주사당일기분별이생리염수(1.5 ml/d)、라격렬동(5 mg/kg급2.5 mg/kg)매일1차관위.21 d후측정각조대서폐동맥평균압(mPAP),취폐조직관찰폐소동맥주위염증평분,측정폐소동맥관벽중막후도점관벽외경백분비(WT％),매련면역흡부(ELISA)법측정폐조직균장백세포분소6(IL-6)、종류배사인자α(TNF-α)화단핵세포추화단백1(MCP-1)수평.결과 라격렬동고、저제량간예조mPAP[ (27±4)、(28 ±4) mm Hg(1 mm Hg =0.133 kPa)]화WT％(13.1％±3.9％、16.7％±1.7％)교모형조[(37±5) mm Hg화45.5％±5.5％]명현저(P＜0.01),단잉고우대조조[(17±3)mm Hg화8.9％±2.3％](P＜0.05화P＜0.01)；라격렬동고、저제량간예조폐소동맥주위염증평분、폐조직균장IL-6、TNF-α급MCP-1수평균명현저우모형조(균P＜0.01)；라격렬동고제량간예조각항지표교저제량간예조유강저추세(P＞0.05).결론 라격렬동조기응용가연완야백합감유도적대서동맥형폐동맥고압형성급폐혈관중구,해작용가능여기항염작용유관,기대폐혈관적보호작용여제량유관.
Objective To investigate the protective effects of rosiglitazone intervention on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and the possible mechanisms.Methods Thirty-two Sprague-Dawley rats were randomly divided into 4 groups:control group with a subcutaneous injection of normal saline.PAH group,high-dose and low-dose rosiglitazone intervention groups all with a subcutaneous injection of MCT and then gastric infusion of normal saline ( 1.5 ml/d),rosiglitazone (5,2.5 mg· kg-1 · d-1).At Day 21,the mean pulmonary arterial pressure (mPAP) was detected by right heart catheter. Then rats were sacrificed and their lungs extracted. Perivascular inflammation was scored with the subjective scale of 0 to 4.The tunica media thickness percentage of small pulmonary arteries ( WT％ ) of rats was calculated.Interleukin 6 ( IL-6),tumor necrosis factor alpha ( TNF-α) and monocyte chemotactic protein 1 (MCP-1) of lung tissue were detected by enzyme-linked immunosorbent assay (ELISA).Results Compared with the PAH group ( ( 37 ± 5 ) mm Hg ( 1 mm Hg =0.133 kPa),45.5％ ±5.5％),the mPAP and WT％ of the high-dose ((27 ±4) mm Hg,13.1％ ±3.9％ ) and low-dose ( ( 28 ± 4 ) mm Hg, 16.7％ ± 1.7％ ) rosiglitazone intervention group were significantly lower ( P ＜ 0.01 ),but were still higher than those of the control group ( ( 17 ± 3 ) mm Hg,8.9％ ± 2.3％ ) ( P ＜ 0.05 or P ＜ 0.01 ).The perivascular inflammation score and levels of IL-6,TNF-α,MCP-1 of high-dose and low-dose rosiglitazone intervention groups were significantly lower than those of the PAH group (P ＜0.01 ).Compared with the low-dose rosiglitazone intervention group,all the above indices of the high-dose rosiglitazone intervention group appeared much lower (P ＞ 0.05 ).Conclusion The protective effects of rosiglitazone against MCT-induced PH are correlated with drug dose and may be due to the inhibition of inflammation.