CAJ | 학술논문

目的观察丹参酮ⅡA磺酸钠(STS)对野百合碱致肺动脉高压大鼠模型的影响,探讨STS对肺动脉平滑肌组织中过氧化物酶体增殖物激活受体(PPAR)γ蛋白表达的影响.方法 SD大鼠20只按随机数字表法分为对照组、对照+ STS组、野百合碱组和野百合碱+STS组,每组5只.野百合碱组和野百合碱+ STS组使用野百合碱诱导建立大鼠肺动脉高压模型,对照+STS组和野百合碱+ STS组给予STS干预21 d,右心测压法检测右心室收缩压(RVSP)及平均压(mRVP);计算右心肥厚指数[RV/(LV+S)];取右肺组织行HE染色并测量小动脉血管管腔,计算血管中膜厚度百分比(WT％),Western blot法检测远端肺动脉平滑肌组织中PPARγ蛋白的表达.结果与野百合碱组[(81.2±1.9)、(28.6±2.0) mmHg(1 mmHg=0.133 kPa)]比较,野百合碱+STS组大鼠RVSP和mRVP降低[(35.4±8.3)、(14.1±5.4)mmHg(P ＜0.05)].对照组和对照+STS组的右心肥厚指数分别为0.33±0.02和0.34±0.02,野百合碱组明显较高(0.57 ±0.04,P＜0.05),野百合碱+STS组与野百合碱组相比较低(0.43 ±0.02,P＜0.05).与对照组比较,野百合碱组血管腔占血管区域的比值从(56±3)％降至(27±6)％,WT％由(20±4)％增加至(40±3)％,(P＜0.05),野百合碱+STS组血管腔占血管区域的比值和WT％分别为(39.0±2.0)％和(31.0±2.0)％,与野百合碱组比较差异有统计学意义(P＜0.05).野百合碱组大鼠肺动脉平滑肌组织PPARγ蛋白与对照组的相对表达量为(48±4)％,差异有统计学意义(P＜0.05).野百合碱+ STS组大鼠肺动脉平滑肌组织中PPARγ蛋白的表达为正常对照的(102±3)％,与野百合碱组相比表达增加(P＜0.05).结论 STS能显著降低野百合碱诱导的肺动脉高压大鼠模型的右心室收缩压、平均压、右心室肥厚指数,改善肺血管重塑,其机制可能与诱导PPARγ蛋白表达有关.
목적 관찰단삼동ⅡA광산납(STS)대야백합감치폐동맥고압대서모형적영향,탐토STS대폐동맥평활기조직중과양화물매체증식물격활수체(PPAR)γ단백표체적영향.방법 SD대서20지안수궤수자표법분위대조조、대조+ STS조、야백합감조화야백합감+STS조,매조5지.야백합감조화야백합감+ STS조사용야백합감유도건립대서폐동맥고압모형,대조+STS조화야백합감+ STS조급여STS간예21 d,우심측압법검측우심실수축압(RVSP)급평균압(mRVP);계산우심비후지수[RV/(LV+S)];취우폐조직행HE염색병측량소동맥혈관관강,계산혈관중막후도백분비(WT％),Western blot법검측원단폐동맥평활기조직중PPARγ단백적표체.결과 여야백합감조[(81.2±1.9)、(28.6±2.0) mmHg(1 mmHg=0.133 kPa)]비교,야백합감+STS조대서RVSP화mRVP강저[(35.4±8.3)、(14.1±5.4)mmHg(P ＜0.05)].대조조화대조+STS조적우심비후지수분별위0.33±0.02화0.34±0.02,야백합감조명현교고(0.57 ±0.04,P＜0.05),야백합감+STS조여야백합감조상비교저(0.43 ±0.02,P＜0.05).여대조조비교,야백합감조혈관강점혈관구역적비치종(56±3)％강지(27±6)％,WT％유(20±4)％증가지(40±3)％,(P＜0.05),야백합감+STS조혈관강점혈관구역적비치화WT％분별위(39.0±2.0)％화(31.0±2.0)％,여야백합감조비교차이유통계학의의(P＜0.05).야백합감조대서폐동맥평활기조직PPARγ단백여대조조적상대표체량위(48±4)％,차이유통계학의의(P＜0.05).야백합감+ STS조대서폐동맥평활기조직중PPARγ단백적표체위정상대조적(102±3)％,여야백합감조상비표체증가(P＜0.05).결론 STS능현저강저야백합감유도적폐동맥고압대서모형적우심실수축압、평균압、우심실비후지수,개선폐혈관중소,기궤제가능여유도PPARγ단백표체유관.
Objective To investigate the effect of sodium tanshinone Ⅱ A sulfonate (STS) on rat right ventricular systolic pressure (RVSP),mean right ventricular pressure (MRVP),right ventricular hypertrophy index [RV/(LV + S)],pulmonary vascular remodeling,and PPARγ protein expression in pulmonary artery smooth muscle of monocrotaline (MCT) induced rat pulmonary hypertension model.Methods The pulmonary hypertension model was established by subcutaneously injection of MCT,and the rats were treated with or without STS for 21 days.After that,RVSP,mRVP and RV/(LV + S) were measured.Lung histopathological sections were prepared,and the lumen area,the wall thickness and arterial radius of pulmonary arteries were quantified using the Image Pro Plus 6.0 software.PPARγ protein expression in rat pulmonary artery smooth muscle was detected by Western blot.Results Compared with control group,the RVSP,mRVP were significantly increased in MCT group (P ＜ 0.05),while in the MCT +STS group,it was decreased from (81.2±1.9) and (28.6±2.0) mmHgto (35.4±8.3) and (14.1 ±5.4) mmHg,respectively (P ＜ 0.05).The RV/(LV + S) of MCT group was (0.57 ± 0.04),markedly higher than those of control group and control + STS group (0.33 ±0.02) and (0.34 ±0.02),respectively,P ＜ 0.05,while in MCT + STS group,the RV/(LV + S) was (0.43 ± 0.02),lower than that of MCT group (P ＜ 0.05) ;The luminal area/total area of MCT group decreased to (27 ± 6) ％ compared with control rats (56.00 ± 3.00) ％ (P ＜ 0.05).The wall thickness/artery radius (WT％) of MCT group increased from (20±4)％ (control group) to(40 ±3)％ (P＜0.05).In MCT +STS treated rats,luminal area/ total area and WT％ were (39.0 ± 2.0)％ and (31.0 ± 2.0)％,both statistically different from MCT group (P ＜ 0.05).The level of PPARγ protein in pulmonary artery smooth muscle of MCT group was (48 ± 4) ％,lower than control group (100 ± 0) ％ (P ＜ 0.05).In the MCT + STS group,PPARγ protein expression was recovered (102 ± 3) ％,(P ＜ 0.05).Conclusion STS markedly decreased RVSP,MRVP,RV/(LV + S)and pulmonary vascular remodeling in MCT induced pulmonary hypertension rat,and PPARγ might be targeted as a key molecule during STS treatment.