丹参酮ⅡA在低氧诱导肺动脉高压中的保护作用  

Protective Effect of Tanshinone IIA in Hypoxic-Induced Pulmonary Hypertension

作　　者：刘礼姣 邱庆竹 郑均敏 谢利剑[1] Liu Lijiao;Qiu Qingzhu;Zheng Junmin;Xie Lijian(Children's Hospital of Shanghai Jiaotong University,Children's Hospital of Shanghai,Shanghai 200062,China)

机构地区：[1]上海交通大学附属儿童医院,上海市儿童医院,上海200062

出　　处：《儿科药学杂志》2021年第8期1-6,共6页Journal of Pediatric Pharmacy

基　　金：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。

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15只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醛(MDA)及超氧化物歧化酶(SOD)水平。取肺动脉平滑肌细胞(PASMCs)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活性下降,MDA含量增加(P<0.05);与低氧组比较,低氧+TanⅡA组小鼠肺组织中SOD活性增加,MDA含量降低(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值增加(P<0.05);与低氧组比较,低氧+TanⅡA组PASMCs中P-Akt/Akt值降低(P<0.05)。结论:TanⅡA具有保护低氧诱导PAH的作用,可能与TanⅡA可降低低氧PAH中氧化应激水平及抑制低氧PASMCs中磷脂酰肌醇-3激酶/丝氨酸/苏氨酸蛋白激酶(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。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.

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 

分 类 号：R544.1[医药卫生—心血管疾病]