CXCL14在慢性危重症模型小鼠心功能损伤中的作用  

Role of CXCL14 in cardiac dysfunction in a chronic critically illness model of mice

作　　者：周诗涵 曾龙欢 徐汉乔 赵东 郑永科 ZHOU Shi-han;ZENG Long-huan;XU Han-qiao;ZHAO Dong;ZHENG Yong-ke(The Fourth Clinical Medical College of Zhejiang Chinese Medical University,Hangzhou,Zhejiang 310053,China;The Intensive Care Unit of Hangzhou Geriatric Hospital,Hangzhou,Zhejiang 310022,China)

机构地区：[1]浙江中医药大学第四临床医学院,杭州310053 [2]杭州市老年病医院重症支持科,杭州310022

出　　处：《浙江中西医结合杂志》2024年第3期219-223,共5页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：杭州市科技发展计划项目(No.20201203B198)。

摘　　要：目的 探索CXC趋化因子配体14(CXCL14)在慢性危重症(CCI)模型小鼠心功能损伤中的作用。方法 采用盲肠结扎穿刺术(CLP)诱导脓毒血症建立CCI小鼠模型。24只C57BL/6小鼠按照随机数字表法分成假手术组、CCI组、CCI+CXCL14组和CCI+Anti-CXCL14组,每组6只。CLP后12 d,采用M型超声心动图记录各组小鼠左心室射血分数(LVEF),酶联免疫吸附测定(ELISA)检测脑钠素(BNP)水平评估小鼠心功能。采用苏木精-伊红(HE)染色法观察心肌组织,比较各组小鼠心肌细胞排列和纤维化情况。采用ELISA法检测心肌组织CXCL14表达水平。采用蛋白质印迹法检测小鼠心肌组织纤维化相关蛋白α-平滑肌肌动蛋白(α-SMA)和Ⅲ型胶原蛋白(CollagenⅢ)的表达情况。结果 与假手术组比较,CCI组小鼠LVEF明显降低[(59.17±3.35)%比(74.31±2.16)%,P<0.01],BNP明显升高[(11.27±0.50)比(6.07±0.45),P<0.01],心肌组织病理损伤明显,心肌细胞体积增大,心肌纤维排列紊乱,CXCL14含量明显升高[(0.55±0.02)ng/mg protein比(0.40±0.03)ng/mg protein,P <0.01],心肌纤维化相关蛋白α-SMA [(0.66±0.02)比(0.31±0.05),P <0.01]和CollagenⅢ[(0.64±0.04)比(0.40±0.04),P<0.01]表达增加。与CCI组比较,CXCL14重组蛋白处理可进一步降低小鼠LVEF[(50.97±3.52)%比(59.17±3.35)%,P<0.05],升高BNP水平[(14.73±0.74)比(11.27±0.50),P<0.01],加重心肌组织病理损伤,进一步升高CXCL14含量[(0.75±0.05)ng/mg protein比(0.55±0.02)ng/mg protein,P<0.01]和心肌纤维化相关蛋白α-SMA表达水平[(0.79±0.05)比(0.66±0.02),P<0.05],对CollagenⅢ表达无显著影响[(0.75±0.06)比(0.64±0.04),P>0.05];而CXCL14抗体处理可抑制CCI模型小鼠LVEF下降[(69.29±2.08)%比(59.17±3.35)%,P<0.01],降低BNP水平[(8.77±0.40)比(11.27±0.50),P<0.01],改善心肌组织纤维化,对CXCL14含量无显著影响[(0.54±0.05)ng/mg protein比(0.55±0.02)ng/mg protein,P>0.05],可抑制CCI模型小鼠心肌组织α-SMA[(0.61±0.03)比(0.77±0.04),P<0.01]和CollagenⅢObjective To explore the role of CXC chemotactic factor 14(CXCL14)in cardiac dysfunction in a mouse model of chronic critically illness(CCI).Methods Cecal ligation and puncture(CLP)surgery was used to establish a sepsis-induced CCI model.Twenty-four C57BL/6 mice were randomly divided into sham,CCI,CCI+CXCL14,and CCI+Anti-CXCL14 groups,with 6 mice in each group.At 12 days after CLP,the left ventricular ejection fraction(LVEF)of each group was recorded using M-mode echocardiography,and brain natriuretic peptide(BNP)was measured using enzyme linked immunosorbent assay(ELISA)to evaluate the cardiac function.Cardiac tissues were observed using Hematoxylin and Eosin staining to compare the arrangement and fibrosis of myocardial cells in each group.The expression level of CXCL14 in myocardial tissue was detected using ELISA.Western blot was used to detect the expression of fibrosis-related proteins,includingα-smooth muscle actin(α-SMA)and typeⅢcollagen protein(CollagenⅢ)in myocardial tissue.Results Compared with the sham group,the CCI group exhibited a significant reduction in LVEF(59.17±3.35 vs.74.31±2.16%,P<0.01)and a significant increase in BNP level(11.27±0.50 vs.6.07±0.45,P<0.01).Notably,the CCI group showed significant myocardial tissue pathological damage,increased myocardial cell volume and disordered myocardial fiber arrangement.Moreover,CXCL14 was significantly increased(0.55±0.02 vs.0.40±0.03 ng/mg protein,P<0.01),along with an increase in the expression of the myocardial fibrosis-related proteins,includingα-SMA(0.66±0.02 vs.0.31±0.05,P<0.01)and CollagenⅢ(0.64±0.04 vs.0.40±0.04,P<0.01).Compared with the CCI group,treatment with recombinant CXCL14 protein further reduced LVEF in the CCI model(50.97±3.52 vs.59.17±3.35%,P<0.05),increased BNP level(14.73±0.74 vs.11.27±0.50,P<0.01),exacerbated pathological damage to myocardial tissue,increased CXCL14 level[0.75±0.05 vs.0.55±0.02 ng/mg protein,P<0.01],and increased the levels of myocardial fibrosis-related proteinα-SMA(0.79±0.05 vs.0.66±

关 键 词：小鼠 慢性危重症 心功能损伤 CXC趋化因子配体14 心肌纤维化 

分 类 号：R459.7[医药卫生—急诊医学] R-332[医药卫生—治疗学]