[1]李玉洁,王金丽,郝恒瑞,等.基于Toll样受体4/核因子κB信号通路探讨依那普利对病毒性心肌炎小鼠的保护作用[J].陕西医学杂志,2026,(4):456-461.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.004]
　LI Yujie,WANG Jinli,HAO Hengrui,et al.To investigate the protective effect of enalapril on viral myocarditis in mice based on TLR4/NF-κB signaling pathway[J].,2026,(4):456-461.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.004]
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基于Toll样受体4/核因子κB信号通路探讨依那普利对病毒性心肌炎小鼠的保护作用

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年4期
页码:
456-461
栏目:
基础研究
出版日期:
2026-04-05

文章信息/Info

Title:
To investigate the protective effect of enalapril on viral myocarditis in mice based on TLR4/NF-κB signaling pathway
作者:
李玉洁1; 王金丽2; 郝恒瑞3 ; 纪美霞4 ; 刘丽丽4 ; 高洁林3 ; 秦丽丽3 ; 郭乔志3
（1.邢台医学院附属医院邢台市中心医院心内科一病区，河北 邢台054000；2.河北公安警察职业学院医学部，河北 石家庄050020；3.河北医科大学附属邢台市人民医院儿科，河北 邢台 054000；4.河北医科大学附属邢台市人民医院超声科，河北 邢台054000）
Author(s):
LI Yujie1 ; WANG Jinli2; HAO Hengrui3 ; JI Meixia4 ; LIU Lili4 ; GAO Jielin3 ; QIN Lili3 ; GUO Qiaozhi3
（1.Department of Cardiology,Ward 1,Xingtai Central Hospital Affiliated to Xingtai Medical University,Xingtai 054000，China;2.Medical Department,Hebei Police Vocational College,Shijiazhuang 050020,China;3.Department of Pediatrics,Xingtai People’s Hospital Affiliated to Hebei Medical University,Xingtai 054000，China;4.Department of Ultrasound,Xingtai People’s Hospital Affiliated to Hebei Medical University,Xingtai 054000，China）
关键词:
依那普利; 病毒性心肌炎; 小鼠; TLR4/NF-κB信号通路; 炎症反应; 心功能; 抑炎因子; TLR4抑制剂
Keywords:
Enalapril; Viral myocarditis; Mice; TLR4/NF-κB signaling pathway; Inflammatory response; Cardiac function; Antiinflammatory factors; TLR4 inhibitor
分类号:
R 542.2
DOI:
DOI:10.3969/j.issn.1000-7377.2026.04.004
文献标志码:
A
摘要:
目的：探讨依那普利对病毒性心肌炎小鼠的保护作用及对Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路的影响。方法：选择90只Balb/c雄性小鼠，将小鼠随机分为五组，各18只，即对照组、病毒性心肌炎模型组、依那普利组、阳性对照组、抑制剂组（TLR4抑制剂TAK-242组）。除对照组外，剩余小鼠构建病毒性心肌炎模型，模型建立成功后。对照组和模型组予0.9%氯化钠溶液10 ml/kg灌胃，依那普利组予以20 mg/kg灌胃，阳性药组予以利巴韦林40 mg/kg灌胃，TLR4抑制剂组予TAK24 23 mg/kg腹腔注射（给药频率同灌胃组），均连续给药7 d。干预后，比较各组小鼠血清乳酸脱氢酶（LDH）、谷草转氨酶（AST）、肌酸激酶同工酶（CK-MB）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-7（IL-7）、肿瘤坏死因子-α（TNF-α）及白细胞介素-10（IL-10）、转化生长因子-β（TGF-β）水平和心功能[左室射血分数（LVEF）、左心室收缩末期内径（LVESD）]。行HE染色观察心肌组织结构变化。Western blot法测各组小鼠心肌组织中TLR4、NF-κB蛋白表达。采用Graph Pad Prism 9.0软件绘制血清LDH、AST、CK-MB及炎症因子（IL-1β、IL-6、IL-7、TNF-α、IL-10、TGF-β）水平的柱状图，直观呈现组间差异。结果：与对照组比较，模型组小鼠血清LDH、AST、CK-MB、IL-1β、IL-6、IL-7、TNF-α水平及心肌组织中TLR4、NF-κB蛋白表达升高，IL-10、TGF-β水平降低（均P＜0.05）；依那普利组、阳性对照组、TLR4抑制剂组小鼠血清LDH、AST、CK-MB、IL-1β、IL-6、IL-7、TNF-α水平及心肌组织中TLR4、NF-κB蛋白表达低于模型组，IL-10、TGF-β水平高于模型组，但均未恢复至对照组水平（均P＜0.05）；其中依那普利组与TLR4抑制剂组上述指标比较无统计学差异（均P＞0.05）。与对照组比较，模型组小鼠LVEF降低、LVESD升高，依那普利组、阳性对照组、TLR4抑制剂组小鼠LVEF、LVESD优于模型组，但仍差于对照组（均P＜0.05）。对照组小鼠心肌结构完整，心肌纤维排列有序，无炎症细胞浸润迹象。模型组小鼠心肌纤维发生溶解且成片分布，可见较多炎症细胞浸润。依那普利组、阳性对照组、TLR4抑制剂组小鼠仅部分心肌纤维溶解，炎症细胞浸润情况缓解，病变程度改善。结论：病毒性心肌炎小鼠中，依那普利可减轻心肌损伤及炎症反应，作用途径可能涉及抑制TLR4/NF-κB信号通路的激活，其保护效应与TLR4抑制剂TAK-242相近。
Abstract:
Objective:To explore the protective effect of enalapril on mice with viral myocarditis and its influence on the Tolllike receptor 4 （TLR4）/nuclear factor κB （NF-κB） signaling pathway.Methods：Ninety male Balb/c mice were randomly divided into 5 groups with 18 mice in each group,namely the control group,viral myocarditis model group,enalapril group,positive control group,and TLR4 inhibitor group （TAK-242 group）.Except for the control group,the remaining mice were used to construct a viral myocarditis model.After the model was successfully established,the control group and the model group were given 10 ml/kg of 0.9%NaCl solution by gavage,the enalapril group was given 20 mg/kg by gavage,the positive drug group was given 40 mg/kg of ribavirin by gavage,and the TLR4 inhibitor group was given 3 mg/kg of TAK-242 by intraperitoneal injection （the administration frequency was the same as that of the gavage group for 7 consecutive days）.After the intervention,the levels of serum lactate dehydrogenase （LDH）,aspartate aminotransferase （AST）,creatine kinase isoenzyme （CK-MB）,interleukin1β （IL-1β）,interleukin6 （IL-6）,interleukin7 （IL-7）,tumor necrosis factorα （TNF-α） （proinflammatory factors）,interleukin10 （IL-10）,transforming growth factorβ （TGF-β） （antiinflammatory factors） and cardiac function （left ventricular ejection fraction,LVEF;left ventricular end systolic diameter,LVESD） of mice in each group were compared.HE staining was performed to observe the structural changes of myocardial tissue.The protein expressions of TLR4 and NF-κB in the myocardial tissues of mice in each group were measured by Western Blot.GraphPad Prism 9.0 software was used to draw bar charts of serum LDH,AST,CK-MB and inflammatory factor （IL-1β,IL-6,IL-7,TNF-α,IL-10,TGF-β） levels to intuitively show the differences between groups.Results:Compared with the control group,the levels of serum LDH,AST,CK-MB,IL-1β,IL-6,IL-7,TNF-αand the protein expressions of TLR4 and NF-κB in myocardial tissue of mice in the model group were increased,while the levels of IL-10 and TGF-β were decreased （all P<0.05）.The levels of serum LDH,AST,CK-MB,IL-1β,IL-6,IL-7,TNF-α and the protein expressions of TLR4 and NF-κB in myocardial tissue of mice in the enalapril group,positive control group and TLR4 inhibitor group were lower than those in the model group,and the levels of IL-10 and TGF-β were higher than those in the model group,but none of them recovered to the level of the control group （all P<0.05）.There were no significant differences in the above indicators between the enalapril group and the TLR4 inhibitor group （all P>0.05）.Compared with the control group,the LVEF of mice in the model group was decreased and LVESD was increased.The LVEF and LVESD of mice in the enalapril group,positive control group and TLR4 inhibitor group were better than those in the model group,but still worse than those in the control group （all P<0.05）.The myocardial structure of the mice in the control group was intact,the myocardial fibers were arranged orderly,and there were no signs of inflammatory cell infiltration.In the model group of mice,myocardial fibers were dissolved and distributed in patches,and a large number of inflammatory cells infiltrated.In the enalapril group,positive control group and TLR4 inhibitor group,only partial myocardial fibrinolysis occurred in the mice,the infiltration of inflammatory cells was alleviated,and the degree of lesion improved.Conclusion:In mice with viral myocarditis,enalapril can alleviate myocardial injury and inflammatory response,and its mechanism of action may involve inhibiting the activation of the TLR4/NF-κB signaling pathway,and its protective effect is similar to that of the TLR4 inhibitor TAK-242.

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相似文献/References:

[1]孙艳艳,师艳莉,程浩洋,等.β2-肾上腺素能受体通过β-抑制蛋白/细胞外调节蛋白激酶通路在病毒性心肌炎中的机制研究[J].陕西医学杂志,2025,54(1):52.[doi:DOI:10.3969/j.issn.1000-7377.2025.01.009]
　SUN Yanyan,SHI Yanli,CHENG Haoyang.Mechanism of β2-adrenergic receptor in viral myocarditis through β-arrestin/ERK1/2 pathway[J].,2025,54(4):52.[doi:DOI:10.3969/j.issn.1000-7377.2025.01.009]

备注/Memo

备注/Memo:
国家自然科学基金资助项目（81670345）；河北省中医药管理局科研项目（2021453）
更新日期/Last Update: 2026-04-05