丁酸通过抑制铁死亡对脓毒症相关心肌功能障碍的保护作用研究  

Protective effects of butyrate on sepsis-related myocardial dysfunction through ferroptosis inhibition

作　　者：王世伟 李璐 高良烽 朱长清[1] 熊剑飞[1] WANG Shiwei;LI Lu;GAO Liangfeng;ZHU Changqing;XIONG Jianfei(Department of Emergency,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China;Department of Nutrition,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China)

机构地区：[1]上海交通大学医学院附属仁济医院急诊科,上海200127 [2]上海交通大学医学院附属仁济医院营养科,上海200127

出　　处：《重庆医学》2025年第4期818-823,共6页Chongqing Medical Journal

基　　金：上海市综合医院中西医结合专项(ZHYY-ZXYJHZX-201902)。

摘　　要：目的研究丁酸对脓毒症相关心肌功能障碍的保护作用。方法选取健康8周清洁级雄性SD大鼠30只,将大鼠分为假手术组(SH组,n=10)、脓毒症组(CL组,n=10)和丁酸组(BU组,n=10)。CL组和BU组采用盲肠结扎穿孔(CLP)建立脓毒症模型,SH组进行相同步骤的手术操作,但不行盲肠结扎、穿孔。SH组和CL组术后30 min内采用生理盐水5 mL灌胃,BU组采用丁酸盐(500 mg/kg)生理盐水溶液5 mL灌胃。比较干预后3组间心输出量(CO)、射血分数(EF)、心肌组织苏木精-伊红(HE)染色病理损伤、心肌电镜线粒体损伤、血清脑钠肽(BNP)、肌钙蛋白I(cTnI)、血清丁酸水平,Western blot检测心肌组织长链酰基辅酶A合成酶4(ACSL4)、谷胱甘肽过氧化物酶4(GPX4)表达情况。结果干预后,CL组大鼠BNP、cTnI水平高于SH组,CO、EF低于SH组,差异有统计学意义(P<0.05);BU组大鼠BNP、cTnI水平低于CL组,CO、EF水平高于CL组,差异有统计学意义(P<0.05)。HE染色显示,CL组心脏组织炎症细胞浸润程度及心肌细胞水肿程度均大于SH组,而BU组心脏组织炎症细胞浸润较CL组减轻。CL组线粒体膜完整性受损,线粒体嵴不清晰,线粒体肿胀、空泡变性、破裂等;BU组线粒体损伤较CL组减轻。CL组、SH组、BU组丁酸水平由低到高分别为(61.7±21.6)、(95.3±16.6)、(302.2±49.7)μg/mL,差异有统计学意义(P<0.05)。CL组ACSL4表达水平高于SH组,GPX4表达水平低于SH组,差异有统计学意义(P<0.05);BU组ACSL4表达水平低于CL组,GPX4表达水平高于CL组,差异有统计学意义(P<0.05)。结论丁酸能改善脓毒症大鼠心肌损伤,这种保护作用可能与丁酸抑制心肌组织铁死亡相关。Objective To investigate the protective effects of butyrate on sepsis-related myocardial dysfunction.Methods Thirty healthy 8-week-old male Sprague-Dawley rats were randomly divided into three groups:sham operation group(SH,n=10),sepsis group(CL,n=10),and butyrate group(BU,n=10).The CL and BU groups underwent cecal ligation and puncture(CLP)to establish sepsis models,while the SH group received the same surgical procedure without cecal ligation or puncture.Within 30 minutes post-operation,the SH and CL groups received 5 mL normal saline via gavage,whereas the BU group was administered 5 mL sodium butyrate solution(500 mg/kg)in normal saline.Cardiac output(CO)and ejection fraction(EF)were compared among the three groups.Myocardial histopathological injury was assessed by HE staining,and mitochondrial ultrastructural damage was observed by electron microscopy.Serum levels of brain natriuretic peptide(BNP),cardiac troponin I(cTnI),and butyrate were compared among groups.Western blot analysis was performed to detect and compare the expression levels of long-chain acyl-CoA synthetase 4(ACSL4)and glutathione peroxidase 4(GPX4)in myocardial tissues.Results After intervention,the BNP and cTnI levels in the CL group were higher than those in the SH group,while CO and EF were lower than those in the SH group(P<0.05).The BNP and cTnI levels in the BU group were lower than those in the CL group,whereas CO and EF levels were higher than those in the CL group(P<0.05).HE staining of myocardial tissues revealed more severe inflammatory cell infiltration and myocardial cell edema in the CL group compared with the SH group,while the BU group showed reduced inflammatory cell infiltration.Mitochondrial membrane integrity was impaired in the CL group manifested by unclear cristae,swelling,vacuolar degeneration and rupture,whereas mitochondrial damage was attenuated in the BU group.Serum butyrate levels were measured as(61.7±21.6)μg/mL,(95.3±16.6)μg/mL and(302.2±49.7)μg/mL in the CL,SH and BU groups respectively(P<0.05).The ACSL

关 键 词：脓毒症 心肌损伤 铁死亡 丁酸 

分 类 号：R542.2[医药卫生—心血管疾病]