Department of Nanlou Traditional Chinese Medicine and Acupuncture, Chinese People's Liberation Army General Hospital, Beijing, 100853, China.
Department of Traditional Chinese Medicine, Chinese People's Liberation Army General Hospital, Beijing, 100853, China.
Chin J Integr Med. 2020 Dec;26(12):913-920. doi: 10.1007/s11655-020-3229-x. Epub 2020 May 11.
To investigate the effect of early intervention of Tongxinluo (, TXL) on right ventricular function (RVF) of rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT).
A total of 30 adult male Sprague-Dawley rats were assigned to 5 groups with complete random experiment design: Sham group (Sham), MCT group, TXL group, sildenafil (SIL) group and combination group (TXL+SIL), 6 rats in each group. Rats were injected with 50 mg/kg MCT solution for inducing PAH model except for those in the sham group. From the day of modeling, rats of TXL, SIL and TXL+SIL groups were given TXL (1.2 g/kg), SIL (10 mg/kg) and combination solution (TXL:1.2 g/kg, SIL: 10 mg/kg) respectively, and rats in Sham and MCT groups were given normal saline (5 mL/kg). The samples were collected and tested after 21 consecutive days of intragastric administration. Echocardiography was used to measure the related indices of RVF, including pulmonary arterial flow spectrum, pulmonary artery diameter (PAD), right ventricular wall thickness (RVWT), right ventricular diameter (RVD), tricuspidannular plane systolic excursion (TAPSE), right atrium transverse diameter (RAT), and inferior vena cava diameter (IVCD). Elastic Verhoeff-Van Gieson staining was adopted to measure the percentage of wall thickness (WT%) of pulmonary arteriols. Hematoxylin-eosin staining was used to measure the cross-sectional area (CSA) of right ventricular cardiomyocytes.
MCT-induced PAH rat model was successfully established. In MCT group the wall of pulmonary arterioles exhibited a prominent-increase thickness, PAD, RVWT, RVD, RAT, IVCD, WT%, right ventricular hypertrophy index (RVHI) as well as CSA of RV cardiomyocyte significantly increased (all P<0.01), and TAPSE markedly decreased (P<0.01). At the same time, TXL prominently improved all of the above indices (all P<0.01). In comparison with SIL, TXL significantly reduced RVD (P<0.05) and decreased CAS of RV cardiomyocytes (P<0.01), but TAPSE in SIL group was much larger than in TXL group (P<0.01). Moreover, TAPSE in TXL+SIL group was larger than that in TXL group (P<0.01), while the two groups performed equally well in terms of the other indices.
Early intervention of TXL could inhibit pulmonary arterioles remodeling, and improve RVF by attenuating right ventricular hypertrophy, and TXL has a stronger effect on inhibiting right ventricular remodeling than SIL.
探讨通心络(TXL)对野百合碱(MCT)诱导的肺动脉高压(PAH)大鼠右心室功能(RVF)的影响。
30 只成年雄性 Sprague-Dawley 大鼠采用完全随机实验设计分为 5 组:假手术组(Sham)、MCT 组、TXL 组、西地那非(SIL)组和联合组(TXL+SIL),每组 6 只。除假手术组外,其余各组大鼠均注射 50mg/kg MCT 溶液诱导 PAH 模型。从建模当天开始,TXL、SIL 和 TXL+SIL 组大鼠分别给予 TXL(1.2g/kg)、SIL(10mg/kg)和联合溶液(TXL:1.2g/kg,SIL:10mg/kg),Sham 和 MCT 组大鼠给予生理盐水(5mL/kg)。连续灌胃 21 天后采集样本并进行检测。超声心动图用于测量 RVF 的相关指标,包括肺动脉血流频谱、肺动脉直径(PAD)、右心室壁厚度(RVWT)、右心室直径(RVD)、三尖瓣环平面收缩期位移(TAPSE)、右心房横径(RAT)和下腔静脉直径(IVCD)。弹性 Verhoeff-Van Gieson 染色测量肺小动脉壁厚度百分比(WT%)。苏木精-伊红染色测量右心室心肌细胞的横截面积(CSA)。
成功建立 MCT 诱导的 PAH 大鼠模型。与 Sham 组相比,MCT 组大鼠的肺小动脉壁显著增厚,PAD、RVWT、RVD、RAT、IVCD、WT%、右心室肥厚指数(RVHI)和 RV 心肌细胞 CSA 均显著增加(均 P<0.01),TAPSE 显著降低(P<0.01)。同时,TXL 明显改善了所有上述指标(均 P<0.01)。与 SIL 组相比,TXL 组的 RVD 显著降低(P<0.05),RV 心肌细胞 CSA 显著减小(P<0.01),但 SIL 组的 TAPSE 明显大于 TXL 组(P<0.01)。此外,TXL+SIL 组的 TAPSE 大于 TXL 组(P<0.01),而两组在其他指标上表现相当。
早期干预 TXL 可抑制肺小动脉重构,通过减轻右心室肥厚改善 RVF,且 TXL 抑制右心室重构的作用强于 SIL。