淫羊藿次苷Ⅱ通过下调ERK1/2-NF-κB信号通路抗野百合碱所致大鼠肺动脉重构  

IcarisideⅡprevents monocrotaline-induced pulmonary artery remodeling by decreasing the ERK1/2-NF-κB signaling pathway in rats

作　　者：李叶丽 吴红丹 付舒 吴雨婷 岳云 杨丹莉 Li Yell;Wu Hongdan;Fu Shu;Wu Yuting;Yue Yun;Yang Danli(Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi Guizhou 563099,China)

机构地区：[1]遵义医学院基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563099

出　　处：《遵义医学院学报》2018年第4期393-398,402,共7页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:81660679);贵州省中医药管理局项目(NO:QZYY2017-011);遵义医学院硕士启动基金资助项目(NO:F-773);基础药理省部共建教育部重点实验室主任基金资助项目(NO:JCYL-Z-002)

摘　　要：目的研究淫羊藿次苷Ⅱ(ICSⅡ)对野百合碱(MCT)所致大鼠肺动脉重构的作用,并探讨其对ERK1/2-NF-κB信号通路的影响。方法 SD大鼠随机分为对照组(Control)、ICS II单纯给药组(Control+ICSⅡ-H,16 mg/kg)、模型组(Model)、ICS II低、中、高剂量组(ICS II-L、ICS II-M、ICS II-H,4、8、16 mg/kg),每组6只。Model组和ICSⅡ低、中、高剂量组经颈背部一次性皮下注射MCT(50 mg/kg)诱导肺动脉重构模型。造模后第1天开始给药至第28天结束。H&E染色观察肺小动脉病理改变;免疫组织化学法检测肺小动脉PCNA、p-ERK1/2、p-NF-κB蛋白的表达。结果与Control组比较,Model组肺小动脉中膜明显肥厚;PCNA、p-ERK1/2、p-NF-κB蛋白的水平明显升高(P<0.05)。与Model组相比,ICSⅡ-M、ICSⅡ-H剂量组肺动脉中膜肥厚显著改善;PCNA、p-ERK1/2、p-NF-κB蛋白的水平明显降低(P<0.05)。结论 ICSⅡ具有抗MCT所致大鼠肺动脉重构的作用,其机制可能与抑制ERK1/2-NF-κB信号通路有关。Objective To investigate the effects of IcarisideⅡ（ICSⅡ） on pulmonary artery remodeling induced by monocrotaline（MCT） in rats and to explore its effect on ERK1/2-NF-κB signaling pathway. Methods SD rats were randomly divided into control group,ICS Ⅱ alone group（Control ＋ ICS II-H,16 mg/kg）,model group,low-dose（ICS II-L,4 mg/kg）,middle-dose（ICS II-M,8 mg/kg） and high-dose（ICS II-H,16 mg/kg） of ICS II treatment group,6 in each group. The rats in the model group and ICS II-L,ICS II-M and ICS II-H groups were injected subcutaneously with MCT to establish the model of pulmonary artery remodeling.On the first day after MCT injection,ICS II was given once a day by intragastric administration for 28 days according to groups. After 28 days of administration,the morphological changes of pulmonary artery were observed by HE stain. The protein levels of PCNA,p-ERK1/2 and p-NF-κB were detected by immunohistochemistry. Results Compared with control group,the medial hypertrophy of pulmonary arterioles were significantly observed,and the expressions of PCNA,p-ERK1/2 and p-NF-κB proteins were increased（P〈0. 05） in model group. Compared with the model group,the medial hypertrophy of pulmonary arterioles were improved,and the protein levels of PCNA,p-ERK1/2 and p-NF-κB were decreased（P〈0. 05） in ICSII-M and ICSII-H groups. Conclusion ICS II can resist pulmonary artery remodeling in MCT-induced rats,which may be related to inhibit the activation of ERK1/2-NF-κB signaling pathway.

关 键 词：淫羊藿次苷Ⅱ 肺动脉重构 细胞外信号调节激酶1/2 核因子ΚB 

分 类 号：R961[医药卫生—药理学]