摘要
目的研究淫羊藿次苷Ⅱ(ICSⅡ)对野百合碱(MCT)所致大鼠肺动脉平滑肌细胞凋亡的影响,并初步探讨其机制。方法 SD大鼠随机分为对照组、模型组、ICSⅡ低、中、高剂量组(4、8、16 mg·kg^(-1))。模型组和ICSⅡ组大鼠经皮下注射MCT诱导肺动脉重构模型,ICSⅡ组于MCT注射后d 1开始给药至d 28结束,模型组和对照组给予等量溶媒。HE染色观察肺小动脉形态学变化;TUNEL染色观察肺动脉平滑肌细胞凋亡情况;蛋白免疫印迹法检测肺组织Bax、Bcl-2和活化的caspase-3蛋白的表达。结果与对照组比,模型组肺小动脉中膜明显增厚;肺动脉平滑肌细胞发生凋亡,TUNEL阳性细胞比率升高(P<0.05);肺组织Bax、Bcl-2、活化的caspase-3的表达上调(P<0.05)。与模型组比,ICSⅡ中、高剂量组肺小动脉中膜变薄;细胞凋亡数均明显增加,TUNEL阳性细胞比率升高(P<0.05);肺组织Bcl-2的表达明显下调(P<0.05),Bax、活化的caspase-3的表达均上调(P<0.05)。结论 ICSⅡ具有促进MCT所致大鼠肺动脉平滑肌细胞凋亡的作用,其机制可能与下调Bcl-2,上调Bax和活化的caspase-3的表达有关。
Aim To investigate the effects of icariside Ⅱ（ICS Ⅱ） on apoptosis related proteins in monocrotaline （MCT）-induced pulmonary artery remodeling rats and to explore the mechanisms. Methods SD rats were randomly divided into control group, model group, ICS Ⅱ low, medium and high dose group （ICS Ⅱ-L, ICS Ⅱ-M, ICS Ⅱ-H, 4, 8, 16 mg·kg^-1 ）. The rats in model and ICSⅡ groups were injected subcutaneously with MCT to establish the model of pulmonary artery remodeling. Then the rats in ICS Ⅱ groups were gavaged once daily from day 1 to day 28 after MCT injection. The other rats in control group and model group were given the equal volume of solvent. HE staining was used to observe the morphological changes of the pulmonary arterioles. TUNEL staining was applied to measure the apoptosis of pulmonary artery smooth muscle cells. Western blot was employed to detect the protein expression of Bax, Bcl-2 and activated caspase-3 in lung tissue. Results Compared with control group, the pulmonary arterioles were thickened significantly, the apoptosis of pulmonary artery smooth muscle cells were observed and the TUNEL positive cells increased （ P 〈0.05）; the protein expressions of Bax, Bcl-2 and activated caspase-3 in lung tissues were up-regulated （ P 〈0.05） in model group. Compared with model group, the pulmonary arterioles were thinned; the TUNEL positive cells increased （ P 〈0.05）; the protein expression of Bcl-2 was significantly reduced （ P 〈0.05）; the protein expression of Bax and activated caspase-3 markedly increased （ P 〈0.05） in ICS Ⅱ-M, H group. Conclusions ICS Ⅱ can promote the apoptosis of pulmonary artery smooth muscle cells induced by MCT in rats, and the mechanism might be related to reducing the expression of Bcl-2 and increasing the expression of Bax and activated caspase-3.
作者
李叶丽
廖娅
钱志强
朱玲
李意奇
杨丹莉
LI Ye-li;LIAO Ya;QIAN Zhi-qiang;ZHU Ling;Li Yi-Qi;YANG Dan-li(Key Lab of Basic Pharmacology of Ministry of Education and Joint International Research Lab of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi Guizhou 563099,China;Dept of Pharmacology,Zunyi Medical University,Zhuhai Campus,Zhuhai Guangdong 519041,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2018年第12期1736-1740,共5页
Chinese Pharmacological Bulletin
基金
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(No JCYL-Z-002)
