柴胡皂苷a对动脉粥样硬化合并抑郁小鼠斑块形成的影响
Effect of saikosaponin a on aortic plaque formation in mice with atherosclerosis and depression
- 上海中医药杂志 2022年56卷第4期 页码：86-91
- 作者机构：
1.上海中医药大学附属普陀医院心血管内科（上海 200062）
2.上海市杨浦区新江湾城社区卫生服务中心全科医学科（上海 200438）
- 作者简介：
陈晨，男，博士，医师，主要从事动脉粥样硬化、抑郁、痴呆的临床与基础研究工作
施佳丽，医师；E-mail：sjl1990_0628@126.com
- 基金信息：上海市卫健委医学重点专科项目(ZK2019A11);上海市普陀区优势学科项目(2019YSXK01);上海中医药大学附属普陀医院院级课题(2019312)
DOI：10.16305/j.1007-1334.2022.2108097
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陈晨,张华,叶健等.柴胡皂苷a对动脉粥样硬化合并抑郁小鼠斑块形成的影响[J].上海中医药杂志,2022,56(04):86-91.
CHEN Chen,ZHANG Hua,YE Jian,et al.Effect of saikosaponin a on aortic plaque formation in mice with atherosclerosis and depression[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(04):86-91.
陈晨,张华,叶健等.柴胡皂苷a对动脉粥样硬化合并抑郁小鼠斑块形成的影响[J].上海中医药杂志,2022,56(04):86-91. DOI： 10.16305/j.1007-1334.2022.2108097.
CHEN Chen,ZHANG Hua,YE Jian,et al.Effect of saikosaponin a on aortic plaque formation in mice with atherosclerosis and depression[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(04):86-91. DOI： 10.16305/j.1007-1334.2022.2108097.
摘要
目的,2,探究抑郁对动脉粥样硬化（AS）的影响和机制，并观察柴胡皂苷a（SSa）对于AS合并抑郁小鼠AS的影响和可能的作用机制。,方法,2,①30只雄性Apoe,-/-,小鼠随机分为AS组（,n,=6）、AS合并抑郁组（,n,=24）。AS组采用高脂饲料喂养8周构建AS小鼠模型。AS合并抑郁组采用高脂饲料喂养8周加慢性轻度不可预见性应激（CUMS）构建AS合并抑郁小鼠模型。造模成功后，比较AS组及AS合并抑郁组小鼠的体质量、血脂［总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）］水平、血清C反应蛋白（CRP）水平，HE染色观察主动脉粥样硬化情况。②AS合并抑郁组（,n,=18）再随机分为生理盐水（SLYS）组（,n,=6）、氟西汀（FXT）组（,n,=6）、SSa组（,n,=6），分别采用SSa、氟西汀、0.9%NaCl溶液5 mg·kg,-1,·d,-1,灌胃4周后，比较3组小鼠的体质量、血脂（TC、LDL-C）水平、血清CRP水平，HE染色观察主动脉粥样硬化情况，免疫组化染色观察主动脉斑块中核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）的含量，并采用悬尾不动实验和强迫游泳实验评价小鼠动物行为学改变情况。,结果,2,①AS合并抑郁组体质量及血清TC、LDL-C、CRP水平高于AS组（,P,<,0.05）；AS合并抑郁组的主动脉粥样硬化程度明显高于AS组。② AS合并抑郁小鼠经相应药物干预4周后，SSa组体质量小于FXT组（,P,<,0.05），SSa组LDL-C水平低于FXT组（,P,<,0.05），SSa组血清CRP水平低于SLYS组（,P,<,0.05），SSa组的主动脉粥样硬化程度较FXT组及SLYS组轻，SSa组的AS斑块内NLRP3表达少于FXT组及SLYS组（,P,<,0.05），SSa组强迫游泳静止时间和悬尾不动静止时间均短于SLYS组及FXT组（,P,<,0.05）。,结论,2,抑郁能够增加体质量和血脂水平，增强炎症反应，加重AS；SSa能够显著改善抑郁，并可能通过减少NLRP3的表达减轻AS合并抑郁小鼠的炎症反应，从而减轻AS。
Abstract
Objective,2,To explore the effect and mechanism of depression on atherosclerosis（AS）， and explore the effect and possible mechanism of saikosaponin a （SSa） on AS in mice with AS complicated with depression.,Methods,2,①Thirty male Apoe,-/-, mice were randomly divided into AS group （,n,=6） and AS complicated with depression group （,n,=24）， and the AS group was administered with high-fat diet for 8 weeks and chronic unpredictable mild stress （CUMS） to establish the AS with depression mouse model. After the model was established successfully， the body mass， blood lipid （TC， LDL-C） level， serum CRP level were compared and aortic atherosclerosis were observed by HE staining and compared between AS group and AS complicated with depression group. ②AS complicated with depression group （,n,=18） was randomly divided into a normal saline （SLYS） group （,n,=6）， a fluoxetine （FXT） group （,n,=6） and a SSa group （,n,=6）. After 4 weeks of intragastric administration of SSa， fluoxetine and 0.9% NaCl solution 5 mg·kg,-1,·d,-1, in the corresponding groups， the body mass， serum levels of blood lipid （TC， LDL-C） and CRP were compared， aortic atherosclerosis was observed by HE staining， NLRP3 content in aortic plaque was observed by immunohistochemical staining， and animal behavior was evaluated by tail suspension test and forced swimming test.,Results,2,①The body mass and serum TC， LDL-C， CRP levels in AS complicated with depression group were higher than those in AS group （,P,<,0.05）； The degree of aortic atherosclerosis in AS complicated with depression group was significantly higher than that in AS group. ②After 4 weeks of intervention with corresponding drugs， the body mass and LDL-C level of AS and depression mice in SSa group were lower than those in FXT group （,P,<,0.05）； serum CRP level of AS and depression mice in SSa group was lower than that in SLYS group （,P,<,0.05）； the degree of aortic atherosclerosis of AS and depression mice in SSa group was milder than that in FXT Group and SLYS Group， and the expression of NLRP3 in AS plaque of AS and depression mice in SSa group was less than that of FXT group and SLYS group （,P,<,0.05）； the rest time of forced swimming and tail suspension in SSa group was shorter than that in SLYS group and FXT group （,P,<,0.05）.,Conclusions,2,Depression can increase body mass and blood lipid level， enhance inflammatory reaction and aggravate AS. SSa can significantly improve depression， and may alleviate AS by reducing the inflammatory reaction of mice with AS and depression through lowering the expression of NLRP3.
关键词
柴胡皂苷a抑郁动脉粥样硬化模型小鼠中药研究
Keywords
saikosaponin adepressionatherosclerosismodel mousetraditional Chinese herbal medicine research
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