迷迭香酸对野百合碱诱导肺动脉高压大鼠的作用及机制  

Effect and mechanism of rosmarinic acid on pulmonary arterial hypertension induced by monocrotaline in rats

作　　者：陈秋宏 杨红 郑琴[2] 郭婧仪 王昱媛 吴奇 CHEN Qiuhong;YANG Hong;ZHENG Qin;GUO Jingyi;WANG Yuyuan;WU Qi(Department of Cardiovascular Medicine,The 2nd Affiliated Hospital of Chengdu Medical College,Nuclear Industry 416 Hospital,Chengdu 610500,China;Department of General Medicine,The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,China;Graduate School,Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]成都医学院第二附属医院,核工业四一六医院心内科,成都610057 [2]成都医学院第一附属医院全科医学科,成都610057 [3]成都医学院研究生院,成都610057

出　　处：《西南医科大学学报》2024年第4期311-315,共5页Journal of Southwest Medical University

基　　金：成都市科技局技术创新研发项目(2022-YF05-01459-SN);四川省中医药管理局科研项目(2023MS177);成都医学院研究生创新基金(YCX2022-01-23);成都市市级医学重点专科项目(CDS2022Z076)。

摘　　要：目的探究迷迭香酸(rosmarinic acid,RosA)对野百合碱(monocrotaline,MCT)诱导肺动脉高压(pulmonary arterialhypertension,PAH)大鼠的影响及其作用机制。方法将30只雄性SD大鼠随机分为对照组(n=10)、肺动脉高压模型组(MCT,n=10)、迷迭香酸治疗组(MCT+RosA,n=10),MCT组和MCT+RosA组使用MCT(60 mg/kg)单次腹腔注射给药构建PAH模型,对照组单次腹腔注射等体积0.9%氯化钠溶液(60 mg/kg)。与对照组相比,MCT组出现唇部和爪部发绀、呼吸急促、进食减少,肺动脉压力升高,RV/(LV+S)升高,肺血管重构等现象,提示PAH造模成功,第2日起对照组和MCT组每天腹腔注射给予0.9%氯化钠(20 mg·kg^(-1)·d^(-1)×21 d),MCT+RosA组每天腹腔注射溶解于0.9%氯化钠的RosA(20 mg·kg^(-1)·d^(-1)×21 d)。用药21天后检测大鼠平均肺动脉压力(mean pulmonaryarterialpressure,mPAP)、右心室肥厚指数(right ventricularhypertrophyindex,RVHI);HE染色测量肺小动脉重构情况;Elisa检测肺组织中丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)表达水平;免疫组化检测肺组织中α肌动蛋白(α-smooth muscle actin,α-SMA)、增殖细胞核抗体(proliferating cellnuclearantigen,PCNA)表达水平。结果与MCT组相比,MCT+RosA组mPAP、RVHI降低,肺动脉重构及肺血管纤维化减少,肺小动脉α-SMA、PCNA表达量降低,肺组织SOD表达水平显著增加,MDA表达水平显著减少,差异均具有统计学意义(P<0.05)。结论RosA可以降低MCT诱导PAH大鼠的右心室收缩压、改善右心室肥厚和肺血管重构,并可能与其降低肺组织氧化应激和肺血管α-SMA、PCNA表达水平有关。Objective To investigate the effect of rosmarinic acid(RosA)on monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH)in rats and its mechanism.Methods Thirty male SD rats were randomly divided into control group(n=10),PAH model group(n=10)and rosmarinic acid treatment group(n=10).The PAH model was established by single subcutaneous injection of MCT(60 mg/kg).The control group and MCT group were given 0.9%stroke-physiological saline solution by intraperitoneal injection every day,and the RosA group was given rosmarinic acid(20 mg/kg)dissolved in 0.9%stroke-physiological saline solution by subcuta-neous injection.After 21 days,the mean pulmonary arterial pressure(mPAP)and right ventricular hypertrophy index(RVHI)of the rats were detected.Pulmonary arteriole remodeling was measured by HE staining.The expression levels of malondialdehyde(MDA),su-peroxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in lung tissues were detected by Elisa.The expression ofα-smooth muscle actin(α-SMA)and proliferating cell nuclear antigen(PCNA)in lung tissue was detected by immunohistochemistry.Results Compared with MCT group,the rats in MCT+RosA group exhibited significant reductions in mPAP and RVHI,pulmonary artery remod-eling and pulmonary vascular fibrosis were decreased,the expression levels ofα-SMA and PCNA in pulmonary arteriole were de-creased,and the expression level of SOD in lung tissue was significantly increased.The expression level of MDA was significantly de-creased(P<0.05).Conclusion RA could reduce the mPAP,improve right ventricular hypertrophy and pulmonary vascular remodel-ing in MCT-induced PAH rats,which might be associated with inhibition of lung tissue oxidative stress and the expression levels ofα-SMA and PCNA in pulmonary vascular.

关 键 词：迷迭香酸 肺动脉高压 肺血管重构 右心室肥厚 

分 类 号：R366[医药卫生—病理学]