Second affiliated hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China; Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Second affiliated hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Biomed Pharmacother. 2022 Jan;145:112383. doi: 10.1016/j.biopha.2021.112383. Epub 2021 Nov 1.
Hypertension is one of the important causes of cardiovascular diseases, and the imbalance of vascular homeostasis caused by oxidative stress and endothelial inflammation occurs throughout hypertension pathogenesis. Therefore, inhibiting oxidative stress and endothelial inflammation is important for treating hypertension. Tianma Gouteng Decoction (TGD) is a Chinese herbal medicine that is commonly used to treat hypertension in China, and demonstrates clinically effective antihypertensive effects. However, its blood pressure reduction mechanism remains unclear. In this study, we further determined the antihypertensive effects of TGD and revealed its underlying mechanism. We established an AngII-induced hypertension mice model, which was treated with TGD for six weeks. We monitored blood pressure, heart rate, and body weight every week. After six weeks, we detected changes in the structure and function of the heart, the structure of blood vessels, and vasomotor factors. We also detected the expression of oxidative stress and inflammation-related genes. We found that TGD can significantly reduce blood pressure, improve cardiac structure and function, and reverse vascular remodeling, which could be due to the inhibition of oxidative stress and inflammation. We also found that the effect of inhibiting oxidative stress and inflammation could be related to the up-regulation of transcription factor EB (TFEB) expression by TGD. Therefore, we used AAV9 to knock down TFEB and observe the role of TFEB in TGD's antihypertensive and cardiovascular protection properties. We found that after TFEB knockdown, the protective effect of TGD on blood pressure and cardiovascular remodeling in AngII-induced hypertensive mice was inhibited, and that it was unable to inhibit oxidative stress and inflammation. Therefore, our study demonstrated for the first time that TGD could exert anti-oxidative stress and anti-inflammatory effects through TFEB and reverse the cardiovascular remodeling caused by hypertension.
高血压是心血管疾病的重要病因之一，氧化应激和内皮炎症导致的血管稳态失衡贯穿于高血压发病机制的始终。因此，抑制氧化应激和内皮炎症对于治疗高血压具有重要意义。天麻钩藤饮（TGD）是一种中药方剂，常用于治疗中国的高血压，具有临床有效的降压作用。然而，其降压机制尚不清楚。在本研究中，我们进一步确定了 TGD 的降压作用，并揭示了其潜在的作用机制。我们建立了 AngII 诱导的高血压小鼠模型，并用 TGD 处理该模型 6 周。我们每周监测血压、心率和体重。6 周后，我们检测了心脏结构和功能、血管结构以及血管舒缩因子的变化。我们还检测了氧化应激和炎症相关基因的表达。我们发现 TGD 可显著降低血压，改善心脏结构和功能，逆转血管重构，这可能是由于抑制了氧化应激和炎症。我们还发现，抑制氧化应激和炎症的作用可能与 TGD 上调转录因子 EB（TFEB）的表达有关。因此，我们使用 AAV9 敲低 TFEB，并观察 TFEB 在 TGD 降压和心血管保护作用中的作用。我们发现，TFEB 敲低后，TGD 对 AngII 诱导的高血压小鼠的降压和心血管重构的保护作用受到抑制，并且无法抑制氧化应激和炎症。因此，我们的研究首次表明，TGD 可以通过 TFEB 发挥抗氧化应激和抗炎作用，逆转高血压引起的心血管重构。
