机构地区:[1]河北省中医院,石家庄050011 [2]河北中医药大学,石家庄050200 [3]河北省中药组方制剂技术创新中心/河北省高校中药开发与产业化应用技术研发中心,石家庄050200
出 处:《河北中医药学报》2024年第5期1-5,共5页Journal of Hebei Traditional Chinese Medicine and Pharmacology
基 金:河北省重点研发计划项目民生科技专项:No.192777104D。
摘 要:目的:探讨消痰化瘀利窍方(Xiaotan Huayu Liqiao Formula,XHLF)改善慢性间歇性低氧(Chronic Intermittent Hypoxia,CIH)小鼠胸主动脉内皮细胞的损伤作用机制。方法:将24只健康的8周龄雄性C57BL/6N小鼠随机分成常氧组(Con组)、慢性间歇性低氧暴露组(CIH组)、慢性间歇性低氧+消痰化瘀利窍方组(CIH+XHLF组)、常氧+消痰化瘀利窍方组(Con+XHLF组)。CIH组与CIH+XHLF组暴露于间歇性低氧的环境中,CIH+XHLF组和Con+XHLF组每日给予消痰化瘀利窍方灌胃(26.8 g/kg/d),而CIH组与Con组给予同等体积生理盐水,共计处理28 d。采用尾套法监测小鼠血压;HE和Masson染色观察胸主动脉病理改变;检测血清中一氧化氮(NO)、血管内皮生长因子(VEGF)含量;透射电镜观察线粒体形态;Tunel染色观察胸主动脉细胞凋亡情况;免疫组织化学染色检测Cleaved Caspase-3、Bcl-2相关X蛋白(Bax)、B淋巴细胞瘤-2基因(Bcl-2)蛋白表达。结果:与Con组相比,CIH组小鼠血压出现升高(P<0.05);血管内膜不平整,细胞核排列紊乱,弹性纤维减少;血清中VEGF水平升高,NO水平下降(P<0.05);线粒体皱缩、嵴断裂;凋亡水平增加,Cleaved Caspase-3、Bax蛋白表达增强,Bcl-2蛋白表达减弱(P<0.05)。与CIH组相比,CIH+XHLF组小鼠血压下降(P<0.05),血管内皮功能和损伤改善(P<0.05),血管内皮线粒体损伤改善,凋亡水平下降(P<0.05)。结论:XHLF可能通过抑制凋亡改善CIH暴露引起的胸主动脉血管损伤和功能障碍。Objective:To investigate the protective mechanism of Xiaotan Huayu Likiao Formula(XHLF)in improving thoracic aortic endothelial cell injury in mice with chronic intermittent hypoxia(CIH).Methods:Twenty-four healthy male C57BL/6N mice aged 8 weeks were randomly divided into four groups:normoxia group(Con),chronic intermittent hypoxia exposure group(CIH),CIH+XHLF group,and Con+XHLF group.The CIH group and the CIH+XHLF group were exposed to an intermittent hypoxic environment.The CIH+XHLF and Con+XHLF groups were administered XHLF daily by gastric lavage(26.8 g/kg/d),while the CIH and Con groups were given an equal volume of normal saline for a total of 28 days.The tail-cuff method was used to monitor the mouse blood pressure;HE and Masson staining to observe the pathological changes in the thoracic aorta;The serum levels of nitric oxide(NO)and vascular endothelial growth factor(VEGF)were measured.Mitochondrial morphology was observed under transmission electron microscopy.TUNEL staining was used to detect apoptosis of thoracic aortic cells;Immunohistochemical staining to detect the expression of Cleaved Caspase-3,Bcl-2-associated X protein(Bax),and B-cell lymphoma-2 gene(Bcl-2)proteins.Results:Compared with the Con group,the systolic blood pressure of mice in the CIH group increased after 21 days(P<0.05).The vascular intima was uneven,the nuclear arrangement was disordered,and the elastic fibers were reduced.The level of VEGF in the serum increased,while the level of NO decreased(P<0.05).Mitochondria showed shrinkage and cristae fracture.The apoptosis level increased,and the expressions of Cleaved Caspase-3 and Bax proteins were enhanced,while the expression of Bcl-2 protein was weakened(P<0.05).Compared with the CIH group,the blood pressure of mice in the CIH+XHLF group decreased(P<0.05),and vascular endothelial function and injury improved(P<0.05).Vascular endothelial mitochondrial damage was improved,and the apoptosis level decreased(P<0.05).Conclusion:XHLF may improve thoracic aortic vascular injury and dysfunc
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