Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China.
Ningxia Hui Medicine Modern Engineering Research Center and Collaborative Innovation Center, Ningxia Medical University, Yinchuan 750004, China.
Molecules. 2018 May 26;23(6):1274. doi: 10.3390/molecules23061274.
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. However, whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored. To test our hypothesis, we aimed to investigate the effects of betaine on monocrotaline-induced PAH in rats and attempted to further clarify the possible mechanisms.
PAH was induced by monocrotaline (50 mg/kg) and oral administration of betaine (100, 200, and 400 mg/kg/day). The mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricle hypertrophy index were used to evaluate the development of PAH. Hematoxylin and eosin staining and Masson staining were performed to measure the extents of vascular remodeling and proliferation in fibrous tissue. Monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were also detected by immunohistochemical staining. Nuclear factor-κB (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were assessed by Western blot.
This study showed that betaine improved the abnormalities in right ventricular systolic pressure, mean pulmonary arterial pressure, right ventricle hypertrophy index, and pulmonary arterial remodeling induced by monocrotaline compared with the PAH group. The levels of MCP-1 and ET-1 also decreased. Western blot indicated that the protein expression levels of NF-κB, TNF-α, and IL-1β significantly decreased ( < 0.01).
Our study demonstrated that betaine attenuated PAH through its anti-inflammatory effects. Hence, the present data may offer novel targets and promising pharmacological perspectives for treating monocrotaline-induced PAH.
肺动脉高压（PAH）的特征是肺血管阻力增加，导致右心衰竭和死亡。最近的研究表明，慢性炎症过程参与了 PAH 的发病机制。几项研究表明，甜菜碱具有出色的抗炎作用。然而，甜菜碱是否通过抑制肺部炎症反应对 PAH 发挥保护作用仍需探讨。为了验证我们的假设，我们旨在研究甜菜碱对野百合碱诱导的大鼠 PAH 的影响，并试图进一步阐明可能的机制。
野百合碱（50mg/kg）诱导 PAH，同时给予甜菜碱（100、200 和 400mg/kg/天）口服。平均肺动脉压、右心室收缩压和右心室肥厚指数用于评估 PAH 的发展。苏木精和伊红染色和 Masson 染色用于测量血管重塑和纤维组织增生的程度。通过免疫组织化学染色检测单核细胞趋化蛋白-1（MCP-1）和内皮素-1（ET-1）。通过 Western blot 评估核因子-κB（NF-κB）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）。
本研究表明，与 PAH 组相比，甜菜碱改善了野百合碱引起的右心室收缩压、平均肺动脉压、右心室肥厚指数和肺动脉重塑的异常。MCP-1 和 ET-1 的水平也降低了。Western blot 表明 NF-κB、TNF-α 和 IL-1β 的蛋白表达水平显著降低（<0.01）。
我们的研究表明，甜菜碱通过抗炎作用减轻 PAH。因此，本研究数据可能为治疗野百合碱诱导的 PAH 提供新的靶点和有前景的药理学观点。
