| 摘要: |
| 目的：通过低氧诱导肺动脉高压（PAH）小鼠及细胞模型，探讨丹参酮IIA（TanIIA）对PAH的疗效及可能的作用机制。方法：选取C57BL6雄性小鼠随机分为常氧组、低氧组及低氧+TanIIA组各5只。4周后采用右心导管法检测小鼠右心室压力，行肺组织氧化苏木精伊红染色法（HE）染色，采用硫代巴比妥酸（TBA）法和WST-8法检测肺组织中丙二醇（MDA）及超氧化物歧化酶（SOD）水平。取肺动脉平滑肌细胞（hPASMCs）随机分为常氧组、低氧组和低氧+TanIIA组，24 h后采用蛋白免疫印迹（WB）实验检测Bax、P62、Akt及P-Akt蛋白表达水平。结果：与常氧组小鼠比较，低氧组右心室收缩压升高（P<0.05）；与低氧组小鼠比较，低氧+TanIIA组右心室收缩压降低（P<0.05）。低氧组较常氧组肺血管明显重构，与低氧组比较，低氧+TanIIA组肺血管重构程度减轻；与常氧组比较，低氧组肺组织中SOD下降，MDA增加（P<0.05）；与低氧组比较，低氧+TanIIA组小鼠肺组织中SOD增加，MDA降低（P<0.05）。与常氧组比较，低氧组PASMCs中Bax蛋白表达降低，P62蛋白表达增加（P<0.05）；与低氧组比较，低氧+TanIIA组PASMCs中Bax蛋白表达增加，P62蛋白表达降低（P<0.05）。与常氧组比较，低氧组PASMCs中P-Akt/Akt比值增加（P<0.05）；与低氧组比较，低氧+TanIIA组PASMCs中P-Akt/Akt比值降低（P<0.05）。结论：TanIIA具有保护低氧PAH的作用，可能与TanIIA可减轻低氧PAH中氧化应激水平及抑制低氧PASMCs中PI3K/Akt信号通路的激活，部分逆转低氧状态下PASMCs凋亡的减少，改善PAH中肺血管重构有关。 |
| 关键词: 低氧肺动脉高压 丹参酮IIA 细胞凋亡与自噬 磷脂酰肌醇-3激酶/丝氨酸/苏氨酸蛋白激酶 氧化应激 |
| DOI：doi:10.13407/j.cnki.jpp.1672.108X.2021.08.001 |
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| 基金项目:上海市卫计委中医药事业发展三年行动计划项目,编号ZY(2018-2020)-FWTX-3023 |
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| Protective Effect of Tanshinone IIA in Hypoxic-Induced Pulmonary Hypertension |
| Liu Lijiao1, Qiu Qingzhu1, Zheng Junmin2, Xie Lijian2 |
| (Children’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Children’s Hospital, Shanghai 200062, China) |
| Abstract: |
| Objective: To explore the therapeutic effect of TanIIA on PAH and its possible mechanism through hypoxic-induced PAH mice and cell models. Methods: C57BL6 male mice were randomly divided into the normal oxygen group (5 mice), the hypoxia group (5 mice), and the hypoxia + TanIIA group (5 mice). After 4 weeks, right ventricular pressure was detected by right heart catheter. HE staining of lung tissue was performed. MDA and SOD in lung tissues were detected by TBA and WST-8 methods. hPASMCs cells were randomly divided into the normal oxygen group, hypoxic group and hypoxic +TanIIA group. 24 hours later, the protein expression levels of Bax, P62, Akt and P-Akt were detected by WB experiment. Results: The right ventricular systolic pressure was increased in the hypoxic group compared with the normal oxygen group (P<0.05), and decreased in the hypoxic +TanIIA group compared with the hypoxic group (P<0.05).Compared with the normal oxygen group, the pulmonary vascular remodeling degree of the hypoxia +TanIIA group was significantly reduced compared with the hypoxia group. SOD and MDA in lung tissues of the hypoxic group and the hypoxic +TanIIA group increased and MDA decreased compared to the normal oxygen group (P<0.05). Compared with normal oxygen group, Bax protein expression in PASMCs decreased and P62 protein expression increased in hypoxia group (P<0.05).Compared with the hypoxia group, Bax protein expression in PASMCs increased and P62 protein expression decreased in the hypoxia +TanIIA group (P<0.05).The p-Akt/Akt ratio in PASMCs was increased in the hypoxic group compared with the normal oxygen group (P<0.05), and the P-Akt/Akt ratio was decreased in the hypoxic + TanIIA group compared with the PASMCs in the hypoxic +TanIIA group (P<0.05). Conclusion: TanIIA can protect hypoxic PAH, which may be related to reducing the oxidative stress level in hypoxic PAH, inhibiting the activation of PI3K/Akt signaling pathway in hypoxic PASMCs, and improving pulmonary vascular remodeling in PAH. |
| Key words: hypoxic pulmonary hypertension tanshinone IIA cell apoptosis and autophagy PI3K/Akt oxidative stress |
