CAJ | 학술논문

目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)及其配体对野百合碱诱导的肺动脉高压大鼠肺血管病变的作用及机制.方法将40只SD大鼠随机分为4组:正常对照组、罗格列酮对照组、野百合碱组和罗格列酮干预组.野百合碱组和罗格列酮干预组给予野百合碱60 mg/kg皮下注射;2个对照组给予等体积生理盐水皮下注射.罗格列酮对照组和罗格列酮干预组自注射生理盐水或野百合碱后,给予罗格列酮生理盐水混悬液(4.0 mg· kg-1·d-1)灌胃,正常对照组和野百合碱组每日给予等体积生理盐水灌胃,共4周.以右心导管测定右室收缩压(RVSP)和肺动脉平均压(mPAP),计算右心肥厚指数(RVHI)作为评价右心室肥厚的指标;ELISA法测定血浆NO和内皮素-1(ET-1)水平;采用HE及ElastinVan Gieson染色法观察各级肺动脉的病理改变,测定并计算中膜厚度百分比(WT％)评价血管重塑程度;免疫组织化学法观察PPARγ的表达情况.结果罗格列酮干预组mPAP(28.2±5.3) mmHg、RVHI(0.35±0.05)和WT％ (27.7±7.2)％较野百合碱组明显改善,但仍高于正常对照组.与野百合碱组比较,罗格列酮干预组可升高血浆NO水平(t=2.363,P＜0.05)、降低ET-1水平(t=3.522,P＜0.01),并抑制肺小血管壁的增厚(t=5.192,P＜0.01).结论罗格列酮可通过激活PPARγ改善野百合碱诱导的肺动脉高压大鼠肺血管重塑,并延缓肺动脉高压的进展.
목적 탐토과양화물매체증식물격활수체γ(PPARγ)급기배체대야백합감유도적폐동맥고압대서폐혈관병변적작용급궤제.방법 장40지SD대서수궤분위4조:정상대조조、라격렬동대조조、야백합감조화라격렬동간예조.야백합감조화라격렬동간예조급여야백합감60 mg/kg피하주사;2개대조조급여등체적생리염수피하주사.라격렬동대조조화라격렬동간예조자주사생리염수혹야백합감후,급여라격렬동생리염수혼현액(4.0 mg· kg-1·d-1)관위,정상대조조화야백합감조매일급여등체적생리염수관위,공4주.이우심도관측정우실수축압(RVSP)화폐동맥평균압(mPAP),계산우심비후지수(RVHI)작위평개우심실비후적지표;ELISA법측정혈장NO화내피소-1(ET-1)수평;채용HE급ElastinVan Gieson염색법관찰각급폐동맥적병리개변,측정병계산중막후도백분비(WT％)평개혈관중소정도;면역조직화학법관찰PPARγ적표체정황.결과 라격렬동간예조mPAP(28.2±5.3) mmHg、RVHI(0.35±0.05)화WT％ (27.7±7.2)％교야백합감조명현개선,단잉고우정상대조조.여야백합감조비교,라격렬동간예조가승고혈장NO수평(t=2.363,P＜0.05)、강저ET-1수평(t=3.522,P＜0.01),병억제폐소혈관벽적증후(t=5.192,P＜0.01).결론 라격렬동가통과격활PPARγ개선야백합감유도적폐동맥고압대서폐혈관중소,병연완폐동맥고압적진전.
Objective To investigate the protective effects of peroxisome proliferator-activated receptor gamma (PPARγ) and its agonist on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and the possible molecular mechanisms.Methods Forty Sprague-Dawley (SD) rats were randomly divided into a control group,a rosiglitazone control group,a monocrotaline group and a rosiglitazone intervention group.The rat models of pulmonary hypertension were replicated by subcutaneous injection of monocrotaline (60 mg/kg) by one time in the monocrotaline group and the rosiglitazone intervention group,the other groups were treated with subcutaneous injection of saline.And then rosiglitazone (4.0 mg/kg) was administered by gastric tube in the rosiglitazone control group and rosiglitazone intervention group once daily,at the same time,the control group and monocrotaline group were only administered saline by gastric tube.After 4 weeks,the right ventricular systolic pressure (RVSP) and mean pulmonary aterial pressure (mPAP) were detected by right heart catheter.Right ventricular hypertrophy index (RVHI) was calculated for the assessment of right ventricular hypertrophy.The blood was took from the abdominal aorta for detection of NO and ET-1 levels byELISA and then the lung tissue sections were stained with HE and elastin-van Gieson for histopathological examination and the calculation of tunica media thickness percentage (WT％).Expressions of PPARγ were detected by immunohistochemistry.Results Compared with the monocrotaline group,the mPAP,RVHI and WT％ of rats in rosiglitazone treatment group [(28.2 ± 5.3) mmHg,(0.35 ± 0.05) and (27.7±7.2)％] decreased significantly,but still higher than those of the control group.Rosiglitazone intervention also decreased the plasma ET-1 level (t =3.522,P ＜0.01) and increased the NO level in PAH rats (t =2.363,P ＜0.05),and reversed the hypertrophy of pulmonary artery wall (t =5.192,P ＜ 0.01).Conclusions Rosiglitazone attenuates the pulmonary arterial remodeling in the rat model of monocrotaline-induced pulmonary hypertension and delays the deterioration in PAH through the activation of PPARγ.