2022 年第 1 期 第 17 卷

慢性应激小鼠体内炎症状态以及心脏组织结构改变的相关机制研究

Study on related mechanism of changes of inflammatory state and cardiac structure in chronic stress mice

作者：陶淑慧1李彦明1刘梅颜2任学群1

英文作者：Tao Shuhui1 Li Yanming1 Liu Meiyan2 Ren Xuequn1

单位：1河南大学医学院，河南省开封市475001；2首都医科大学附属北京安贞医院双心医学中心，北京100029

英文单位：1Henan Medical School Henan University Henan Province Kaifeng 475001 China; 2Phyco-cardiology Medical Center Beijing Anzhen Hospital Capital Medical University Beijing 100029 China

关键词：心脏损伤；炎症因子；慢性不可预测温和应激

英文关键词：Cardiacinjury;Inflammatoryfactors;Unpredictablechronicmildstress

• 摘要：

• 目的 探讨小鼠在慢性不可预测温和应激（UCMS）状态下体内炎症状态及心脏功能改变的相关机制。方法 选取无特定病原体级雄性C57BL/6n小鼠30只，完全随机分为对照组、UCMS组及干预组，各10只。干预组小鼠予安神补心六味丸1.5 g/（kg·d）混悬液灌胃，对照组和UCMS组小鼠予等量0.9%氯化钠注射液1次/d灌胃，连续4周。UCMS组和干预组于灌胃4周期间给予UCMS，对照组不予处理。于灌胃前及灌胃后每周测量小鼠体质量。对小鼠进行糖水偏好实验及强迫游泳实验。测定血清白细胞介素1β（IL-1β）、IL-18及IL-10水平。观察心脏组织形态学变化及纤维化情况。结果 行强迫游泳实验后，UCMS组和干预组各死亡1只。灌胃前及灌胃后每周，3组小鼠体质量比较差异均无统计学意义（均P＞0.05）。灌胃4周后，UCMS组糖水偏好指数低于对照组［（0.51±0.20）比（0.94±0.04）］，而干预组（0.80±0.12）高于UCMS组（均P＜0.05）。灌胃4周后，UCMS组不动时间明显长于对照组，挣扎时间明显短于对照组，干预组不动时间明显短于UCMS组，挣扎时间明显长于UCMS组（均P＜0.05）。UCMS组小鼠血清IL-1β、IL-18及IL-10水平均高于对照组，而干预组IL-1β、IL-18水平均低于UCMS组，IL-10水平高于UCMS组（均P＜0.05）。镜下观察各组心脏组织苏木精-伊红染色情况，UCMS组可见心肌纤维排列紊乱，结构破坏，细胞着色不均匀，间质中有大量炎症细胞浸润；干预组心肌纤维结构破坏及炎症细胞浸润程度轻于UCMS组。镜下观察各组心脏组织Masson染色情况，UCMS组心肌纤维化面积大于对照组（30.43% 比10.54%），干预组心肌纤维化面积（19.59%）小于UCMS组。结论  UCMS模型小鼠体内炎症状态及心脏组织结构发生明显改变，可能与UCMS诱发心脏炎症反应有关。

• Objective   To investigate the changes of inflammatory state and cardiac structure in mice under unpredictable chronic mild stress (UCMS). Methods  Thirty specific pathogen free male C57BL/6n mice were selected. They were randomly divided into control group, UCMS group and intervention group, with 10 mice in each group. The intervention group was given Anshen Buxin Liuwei pills 1.5 g/（kg·d） suspension by gavage, and the control group and UCMS group were given the same amount of 0.9% sodium chlorirde injection 1 time/d by gavage, all for 4 weeks. During 4 weeks of gavage, the UCMS group and intervention group were given UCMS and the control group was not treated. Body mass of mice was measured before gavage and every week after gavage. Sugar preference test and forced swimming test were carried out. Serum levels of interleukin-1β (IL-1β), IL-18 and IL-10 were detected. Morphological changes and fibrosis of heart were observed. Results  After forced swimming test, a mouse dead in each UCMS group and intervention group. There were no significant differences in body mass of mice among the three groups before gavage and every week after gavage (all P>0.05). Four weeks after gavage, sugar preference index in the UCMS group was lower than that in the control group［（0.51±0.20） vs （0.94±0.04）］, while that in the intervention group (0.80±0.12) was higher than that in the UCMS group (both P<0.05). Four weeks after gavage, immobility time in the UCMS group was longer than that in the control group and struggle time was shorter than that in the control group, while immobility time in the intervention group was shorter than that in the UCMS group and struggle time was longer than that in the UCMS group (all P<0.05). Serum levels of IL-1β, IL-18 and IL-10 in the UCMS group were higher than those in the control group, levels of IL-1β of IL-18 in the intervention group were lower than those in the UCMS group, and the level of IL-10 in the intervention group was higher than that in the UCMS group (all P<0.05). The hematoxylin-eosin staining of cardiac tissue in each group was observed under microscope. It was showed that the myocardial fibers were disordered, the structure was destroyed, the cells were stained unevenly, and there were a large number of inflammatory cells in the stroma in the UCMS group; the degree of myocardial fiber structure destruction and inflammatory cell infiltration in the intervention group were lighter than those in the UCMS group. The Masson staining of cardiac tissue in each group was observed under microscope. It was showed that the area of myocardial fibrosis in the UCMS group was greater than that in the control group (30.43% vs 10.54%), and that in the intervention group (19.59%) was smaller than that in the UCMS group. Conclusions  The inflammatory state and cardiac tissue structure of UCMS model mice are significantly changed. This suggests that it may be related to the cardiac inflammatory response induced by UCMS.