补肺活血方联合羊膜间充质干细胞移植治疗低氧性肺动脉高压大鼠的增效机制研究

Study on the synergistic mechanism of Lung-nourishing and Blood-activating Formula combined with amniotic mesenchymal stem cell transplantation in treating hypoxic pulmonary hypertension in rats

关键词:  肺动脉高压  补肺活血方  间充质干细胞  内皮-间充质转化

Key words:  pulmonary hypertension  Lung-nourishing and Blood-activating Formula  mesenchymal stem cells  endothelial-mesenchymal transition

摘要:

目的 研究探讨了补肺活血方联合羊膜间充质干细胞（MSC）移植对低氧性肺动脉高压（HPH）大鼠的协同治疗效果及其作用机制。方法 通过构建低氧性肺动脉高压大鼠模型，将造模成功的24只大鼠分为模型组、模型中药组、模型MSC组及模型中药MSC组，分别给予补肺活血方灌胃、MSC尾静脉注射及联合干预。结果 实验结果显示，模型中药MSC组降低右心室肥厚指数（RVHI）、改善肺动脉厚度百分比（WT%）和肺动脉面积百分比（WA%）、抑制内皮-间充质转化相关标志物[α-平滑肌肌动蛋白（α-SMA）、锌指结构转录抑制因子（Snail）、基质金属蛋白酶9（MMP9）]表达、上调内皮细胞标志物血管内皮钙黏蛋白（VE-cadherin）表达，降低炎症因子[血管内皮生长因子（VEGF）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）]水平方面均显著优于其他各组（P < 0.05）。机制研究表明，联合疗法通过抑制内皮间充质转化（EndoMT）过程，改善血管内皮屏障功能，协同调控炎症反应及血管重构，从而有效缓解肺动脉高压病理进展。结论 研究为中西医结合治疗肺动脉高压提供了实验依据，证实补肺活血方与MSC联合应用具有显著的协同增效作用。

Abstract:

Objective This study investigated the synergistic therapeutic effects and explored the underlying mechanisms of the Lung-nourishing and Blood-activating Formula combined with amniotic mesenchymal stem cell (MSC) transplantation in rat models of hypoxic pulmonary arterial hypertension. Methods A hypoxic pulmonary arterial hypertension rat model was established, and 24 successfully modeled rats were divided into four groups: the model group, the traditional Chinese medicine (TCM) group, the stem cell group, and the combined therapy group. The groups received oral administration of the Lung-nourishing and Blood-activating Formula, tail vein injection of MSC, or combined intervention, respectively. Results Results demonstrated that the combined therapy group exhibited greater reductions in right ventricular hypertrophy index (RVHI); improved percentage of pulmonary artery thickness (WT%) and percentage of pulmonary artery area (WA%); suppressed the expression of endothelium-mesenchymal transition (EndoMT)-related markers (α-SMA, Snail, and MMP9); upregulated endothelial cell markers (VE-cadherin); reduced inflammatory factor levels (VEGF, TNF-α, and IL-6) compared with the monotherapy groups (P < 0.05). Mechanistic studies revealed that the combination therapy effectively mitigated pulmonary arterial hypertension progression by inhibiting the EndoMT process, improving vascular endothelial barrier function, and synergistically regulating inflammatory responses and vascular remodeling. Conclusion This study provides experimental evidence for the integrated traditional Chinese and Western medicine strategy in treating pulmonary arterial hypertension, confirming the significant synergistic effect of combining the Lung-nourishing and Blood-activating Formula with MSC.