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温阳利水方对肺动脉高压致右心室衰竭大鼠心室重构的影响
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| 篇名： | 温阳利水方对肺动脉高压致右心室衰竭大鼠心室重构的影响 |
| TITLE： | Impact of Wenyang lishui formula on ventricular remodeling in rats with pulmonary hypertension-induced right heart failure |
| 摘要： | 目的 基于Hippo/Yes相关蛋白（YAP）信号通路探讨温阳利水方对肺动脉高压致右心室衰竭（RHF）大鼠心室重构的影响。方法随机选取10只大鼠，作为对照组；其余63只大鼠通过单次腹膜内注射野百合碱建立肺动脉高压致RHF大鼠模型，并将造模成功的50大鼠随机分为RHF组、温阳利水方低剂量组（4.25g/kg）、温阳利水方高剂量组（17.00g/kg）、呋塞米组（20mg/kg）、温阳利水方高剂量+Hippo/YAP信号通路激活剂组（17.00g/kg的温阳利水方+16mg/kg的PY-60），每组10只。各组大鼠均灌胃或/和尾静脉注射相应药液或生理盐水，每天1次，连续4周。实验期间，观察各组大鼠的一般状况；末次给药后，检测各组大鼠的右室内径、右房内径、舒张末期容积、肺动脉血流加速时间（PAAT）及其与射血时间（ET）的比值（PAAT/ET）、肺动脉压及其与肺动脉血流速度比值（肺动脉压/速度），检测其血浆中脑钠肽、血管紧张素Ⅱ（AngⅡ）水平，观察其右心室组织的病理学变化，并检测胶原容积分数、大肿瘤抑制因子1/2（LATS1/2）和YAP蛋白的磷酸化水平以及PDZ结合基序的转录共激活因子（TAZ）蛋白的表达水平。结果与RHF组比较，温阳利水方低、高剂量组大鼠的毛色、运动及饮食、精神状态等均有所改善，右心室心肌细胞萎缩、炎症细胞增多、胶原沉积、心肌纤维增生等有所减轻；其右室内径、右房内径、舒张末期容积、肺动脉压、肺动脉压/速度、血浆脑钠肽和AngⅡ水平、胶原容积分数、YAP蛋白的磷酸化水平和TAZ蛋白的表达水平均显著降低，PAAT、PAAT/ET、LATS1/2蛋白的磷酸化水平均显著升高（P＜0.05）；PY-60可显著逆转高剂量温阳利水方对上述定量指标的改善作用（P＜0.05）。结论温阳利水方可恢复肺动脉高压致RHF大鼠右心功能，降低其肺动脉压，减轻其心脏组织病理改变，上述作用可能与激活Hippo表达、抑制YAP磷酸化有关。 |
| ABSTRACT： | OBJECTIVE To discuss the impact of Wenyang lishui formula on ventricular remodeling in rats with pulmonary hypertension-induced right heart failure （RHF） based on the Hippo/Yes-associated protein （YAP） signaling pathway. METHODS Ten rats were randomly selected as the control group. The remaining 63 rats were given a single intraperitoneal injection of monocrotaline to establish the pulmonary hypertension-induced RHF model. The 50 rats that successfully underwent the model establishment were randomly divided into the RHF group， low-dose group of Wenyang lishui formula （4.25 g/kg）， high-dose group of the Wenyang lishui formula （17.00 g/kg）， furosemide group （20 mg/kg）， and high-dose group of Wenyang lishui formula+ Hippo/YAP signaling pathway activator group （17.00 g/kg of Δ Wenyang lishui formula+16 mg/kg of PY-60）， with 10 rats in each group. The rats in each group were given the corresponding drug solution or normal saline by gavage or/andtail vein injection， once a day， for 4 consecutive weeks. During the experiment， the general conditions of the rats in each group were observed； after the last administration， the right ventricular diameter， right atrial diameter， end-diastolic volume， pulmonary artery blood flow acceleration time （PAAT） and its ratio to ejection time （ET） （PAAT/ET）， pulmonary artery pressure and its ratio to pulmonary arterial flow velocity （pulmonary artery pressure/velocity） were measured. The plasma levels of brain natriuretic peptide and angiotensin Ⅱ （Ang Ⅱ） were detected. The pathological changes of the right ventricular tissue were observed， and the collagen volume fraction， the phosphorylation levels of the large tumor suppressor 1/2 （LATS1/2） and YAP， and the protein expression of the transcriptional coactivator of PDZ-binding motif （TAZ） were also detected. RESULTS Compared with the RHF group， the rats in Wenyang lishui formula low-dose and high-dose groups showed improved hair color， movement， diet， and mental state. The atrophy of right ventricular myocardial cells， the increase of inflammatory cells， collagen deposition， and hypertrophy of myocardial fibers were significantly alleviated. The right ventricular internal diameter， right atrial internal diameter， end-diastolic volume， pulmonary artery pressure， pulmonary artery pressure/velocity， the plasma levels of brain natriuretic peptide and AngⅡ ， collagen volume fraction， the phosphorylation level of YAP and protein expression of TAZ were significantly decreased， while the PAAT， PAAT/ET and the phosphorylation level of LATS1/2 were significantly increased （P＜0.05）. PY-60 could significantly reverse the improvement effects of high-dose Wenyang lishui formula on the above quantitative indicators （P＜ 0.05）. CONCLUSIONS Wenyang lishui formula can restore the right heart function of pulmonary hypertension-induced RHF rats， reduce their pulmonary artery pressure， alleviate the pathological changes in their cardiac tissues， and the above effects may be related to the activation of Hippo expression and the inhibition of YAP phosphorylation. |
| 期刊： | 2025年第36卷第20期 |
| 作者： | 冯思建；黄燕；邢爱民；袁玫；刘亚芳；王伟明 |
| AUTHORS： | FENG Sijian，HUANG Yan，XING Aimin，YUAN Mei，LIU Yafang，WANG Weiming |
| 关键字： | 温阳利水方；肺动脉高压；右心室衰竭；心室重构；Hippo/YAP信号通路 |
| KEYWORDS： | Wenyang lishui formula； pulmonary hypertension； right heart failure； ventricular remodeling； Hippo/YAP |
| 阅读数： | 2 次 |
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