Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China , Wenzhou Medical University Renji College, Wenzhou, Zhejiang 325035, China.
Am J Chin Med. 2014;42(4):799-816. doi: 10.1142/S0192415X14500517.
Pulmonary arterial hypertension (PAH) is a disease of the small pulmonary arteries characterized by increased vascular resistance. Pulmonary vasoconstriction has been proven to play a pivotal role in PAH. We have previously hypothesized that Panax notoginseng saponins (PNS) might attenuate hypoxia-hypercapnia-induced pulmonary vasoconstriction. The specific objective of the present study was to investigate the role of notoginsenoside R1, a main ingredient of PNS, in this process and the possible underlying mechanism. The third order pulmonary rings from the Sprague-Dawley rats were treated with different concentrations of notoginsenoside R1 (8, 40, and 100 mg/L, respectively) both before and during the conditions of hypercapnia and hypoxia. Contractile force changes in the rings were detected and the optimal concentration (8 mg/L) was selected. Furthermore, an ERK inhibitor, U0126, was applied to the rings. In addition, pulmonary arterial smooth muscle cells (PASMCs) were cultured under hypoxic and hypercapnic conditions, and notoginsenoside R1 was administered to detect the changes induced by ERK1/2. The results revealed biphasic vasoconstriction in rings under hypoxic and hypercapnic conditions. It is hypothesized that the observed attenuation of vasoconstriction and the production of vasodilation could have been induced by notoginsenoside R1. This effect was found to be significantly reinforced by U0126 (p < 0.05 or p < 0.01). ERK expression in the PASMCs under hypoxic and hypercapnic conditions was significantly activated (p < 0.05 or p < 0.01) and the observed activation was attenuated by notoginsenoside R1 (p < 0.05 or p < 0.01). Our findings strongly support the significant role of notoginsenoside R1 in the inhibition of hypoxia-hypercapnia-induced vasoconstriction by the ERK pathway.
肺动脉高压（PAH）是一种以肺小动脉血管阻力增加为特征的疾病。肺血管收缩已被证明在 PAH 中起着关键作用。我们之前假设三七总皂苷（PNS）可能会减轻缺氧高碳酸血症引起的肺血管收缩。本研究的具体目的是研究三七皂苷 R1（PNS 的主要成分之一）在这一过程中的作用及其可能的潜在机制。分别用不同浓度的三七皂苷 R1（分别为 8、40 和 100mg/L）预处理和处理缺氧高碳酸血症条件下的 SD 大鼠三级肺环，检测环的收缩力变化，并选择最佳浓度（8mg/L）。此外，将 ERK 抑制剂 U0126 应用于环。此外，在缺氧高碳酸条件下培养肺动脉平滑肌细胞（PASMCs），并给予三七皂苷 R1，以检测 ERK1/2 诱导的变化。结果显示，在缺氧和高碳酸条件下，环呈双相性血管收缩。假设观察到的血管收缩减弱和血管舒张产生可能是由三七皂苷 R1 引起的。用 U0126 （p<0.05 或 p<0.01）明显增强了这种作用。缺氧高碳酸条件下 PASMCs 中 ERK 的表达明显被激活（p<0.05 或 p<0.01），而三七皂苷 R1 减弱了观察到的激活（p<0.05 或 p<0.01）。我们的研究结果强烈支持三七皂苷 R1 通过 ERK 通路在抑制缺氧高碳酸血症引起的血管收缩中具有重要作用。
