[1]严晓华,王 娜,马 娟,等.阿托伐他汀对小鼠川崎病的治疗作用及机制研究[J].陕西医学杂志,2022,51(6):672-675,696.[doi:DOI:10.3969/j.issn.1000-7377.2022.06.007]
　YAN Xiaohua,WANG Na,MA Juan,et al.Therapeutic effect and mechanism of atorvastatin on Kawasaki disease mice[J].,2022,51(6):672-675,696.[doi:DOI:10.3969/j.issn.1000-7377.2022.06.007]
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阿托伐他汀对小鼠川崎病的治疗作用及机制研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
51
期数:
2022年6期
页码:
672-675,696
栏目:
基础研究
出版日期:
2022-06-05

文章信息/Info

Title:
Therapeutic effect and mechanism of atorvastatin on Kawasaki disease mice
作者:
严晓华1; 王 娜2; 马 娟1; 闫鲜鹏1; 郑千千1
(1.陕西省人民医院,陕西 西安 710068; 2.西安市第九医院儿科,陕西 西安 710054)
Author(s):
YAN Xiaohua; WANG Na; MA Juan; YAN Xianpeng; ZHENG Qianqian
(Shaanxi Provincial People's Hospital,Xi'an 710068,China)
关键词:
川崎病;  阿托伐他汀;  核因子-κB;  基质金属蛋白酶-9;  小鼠模型;  作用机制
Keywords:
Kawasaki disease;  Atorvastatin;  NF-κB;  Matrix metalloproteinase-9;  Mouse model;  Mechanism of action
分类号:
R 725.4
DOI:
DOI:10.3969/j.issn.1000-7377.2022.06.007
文献标志码:
A
摘要:
目的:探讨阿托伐他汀对小鼠川崎病的治疗作用及机制。方法:把小鼠随机分为模型组、对照组、实验组,每组各20只。模型组和实验组在实验时开始给予干酪乳杆菌细胞壁提取物(LCWE)腹腔注射,对照组给予0.9%氯化钠溶液0.5 ml腹腔注射。实验组于实验第5天口服阿托伐他汀10 mg/d,模型组和对照组均腹腔注射等量0.9%氯化钠溶液。在实验第14、28天,每组取8只小鼠行超声心动图检测,并留取心脏标本进行病理分析。通过蛋白质印迹和电泳迁移率实验方法(EMSA)检测心脏组织核因子(NF)-κB表达量及活性。通过蛋白质印迹法和明胶酶谱法检测心脏组织基质金属蛋白酶-9(MMP-9)表达量及活性。结果:LCWE注射后HE染色发现,模型组小鼠冠状动脉局部可见炎性细胞浸润,第14、28天超声心动图检查可见冠状动脉增宽,阿托伐他汀治疗后炎性细胞浸润程度降低,左冠状动脉主干内径减小。模型组第14、28天NF-κB表达量高于对照组和实验组(均P<0.01),实验组和对照组NF-κB表达量比较差异无统计学意义(P>0.05)。模型组第14、28天NF-κB活性明显高于对照组和实验组(均P<0.01),且实验组NF-κB活性明显高于对照组(P<0.05)。模型组第14、28天MMP-9表达量及活性高于对照组和实验组(均P<0.05),实验组和对照组MMP-9表达量及活性比较差异无统计学意义(均P>0.05)。结论:阿托伐他汀对小鼠川崎病具有一定的治疗效果,其作用机制可能是抑制川崎病小鼠模型NF-κB和MMP-9过度表达与激活,从而减少血管炎的发生。
Abstract:
Objective:To investigate the therapeutic effect and mechanism of atorvastatin on Kawasaki disease mice.Methods: The mice were randomly divided into model group,control group and experimental group,with 20 mice in each group.The model group and the experimental group were given lactobacillus casei cell wall extract(LCWE)intraperitoneal injection on day 0 of the experiment,while the control group was given 0.9% sodium chloride solution 0.5 ml intraperitoneal injection in the same way.The experimental group received atorvastatin 10 mg/d orally on the 5th day of the experiment,and the model group and the control group received the same amount of 0.9% sodium chloride solution intraperitoneally.On 14th and 28th days of the experiment,8 mice in each group were examined by echocardiography,and cardiac specimens were collected for pathological analysis.The expression and activity of nuclear factor(NF)-κB in cardiac tissue were measured by Western blot and electrophoretic mobility assay(EMSA).The expression and activity of matrix metalloproteinase-9(MMP-9)in cardiac tissue were measured by Western blot and gelatin zymography.Results:After injection of LCWE,HE staining showed that in the model group,inflammatory cell infiltration was seen locally in the coronary arteries,and coronary artery widening was seen by echocardiography on the 14th and 28th days.The expression of NF-κB in the model group was higher than that in the control group and the experimental group on the 14th and 28th days(all P<0.01),and there was no significant difference in the expression of NF-κB between the experimental group and the control group(P>0.05).NF-κB activity in the model group was significantly higher than that in the control group and the experimental group on the 14th and 28th days(all P<0.01),and NF-κB activity in the experimental group was significantly higher than that in the control group(P<0.05).The expression and activity of MMP-9 in the model group on the 14th and 28th days were higher than those in the control group and the experimental group(all P<0.05).There was no significant difference in the expression and activity of MMP-9 between the experimental group and the control group(all P>0.05).Conclusion:Atorvastatin has a certain therapeutic effect in LCWE-induced Kawasaki disease mouse model.Its mechanism of action may be through inhibiting the overexpression and activation of NF-κB and MMP-9 in Kawasaki disease mouse model,thus reducing the occurrence of vasculitis.

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备注/Memo

备注/Memo:
基金项目:陕西省重点研发计划项目(2019SF-112); 陕西省中医药管理局科研课题(2021-01-ZZ-014)
更新日期/Last Update: 2022-06-06