4-苯基丁酸介导内质网应激对脓毒症大鼠的治疗作用及机制研究  

Study on the therapeutic effect and mechanism of endoplasmic reticulum stress mediated by 4-phenylbutyric acid on septic rats

作　　者：闫智杰[1] 游燕[1] 吴丽丽 YAN Zhijie;YOU Yan;WU Lili(Department of Critical Care Medicine,the Fourth Affiliated Hospital of Nanchang University,Nanchang,Jiangxi,330003,China;Department of Critical Care Medicine,Shenzhen Hospital,University of Hong Kong,Shenzhen,Guangdong,518053,China)

机构地区：[1]南昌大学第四附属医院重症医学科,江西南昌330003 [2]香港大学深圳医院重症医学科,广东深圳518053

出　　处：《当代医学》2024年第23期1-5,共5页Contemporary Medicine

基　　金：江西省卫生健康委科技计划(SKJP220211237)。

摘　　要：目的探究4-苯基丁酸(4-phenylbutyric acid,4-PBA)介导内质网应激(endoplasmic reticulum stress,ERS)对脓毒症大鼠的治疗作用及机制。方法选取60只12周龄无特定病原体(specific pathogen free,SPF)级SD大鼠作为研究对象,随机分为对照组、实验1组、实验2组,每组20只。对照组仅做开腹、盲肠游离及关腹术;实验1组采用盲肠结扎穿孔术(cecal ligation and perforation,CLP)建立脓毒症大鼠模型;实验2组给予腹腔注射120 mg/kg的4-PBA,然后立即进行CLP建立腹膜炎脓毒症大鼠模型。比较3组肠组织及肺和肾血管通透性及ERS标志蛋白[葡萄糖调节蛋白78(glucose regulatory protein 78,GRP78)、CCAAT/增强子结合蛋白同源蛋白(CCAAT enhancer binding protein homologous protein,CHOP)、含半胱氨酸的天冬氨酸蛋白水解酶-12(cysteinyl aspartate specific proteinase-12,caspase-12)、葡萄糖调节蛋白94(glucose regulatory protein 94,GRP94)]、炎症因子[白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)]、核因子-κB(nuclear factor-κB,NF-κB)、同型半胱氨酸(homocysteine,Hcy)表达水平和主动脉血管平滑肌细胞凋亡情况、肠道功能指标[D-乳酸(D-lactate)、内毒素(endotoxin,ET)]、肾脏功能指标[血尿素氮(blood urea nitrogen,BUN)、视黄醇结合蛋白(retinol-binding protein,RBP)、血肌酐(serum creatinine,SCr)、β2-微球蛋白(β2-microglobulin,β2-MG)]。结果实验1组肠组织及肺和肾血管通透性、细胞凋亡指数及GRP78、CHOP、caspase-12、GRP94、IL-6、IL-1β、TNF-α、NF-κB、Hcy、D-lactate、ET、BUN、RBP、SCr、β2-MG水平均高于实验2组与对照组,差异有统计学意义(P<0.05)。实验2组肠组织及肺和肾血管通透性、CHOP、caspase-12、IL-6、IL-1β、TNF-α、细胞凋亡指数、NF-κB、Hcy、D-lactate、ET、BUN、RBP、β2-MG水平均高于对照组,差异有统计学意义(P<0.05)。结论4-PBA可改善内质网应Objective To explore the therapeutic effect and mechanism of endoplasmic reticulum stress(ERS)mediated by 4-phenylbutyric acid(4-PBA)on septic rats.Methods 60 cases of 12-week-old specific pathogen free(SPF)SD rats were randomly divided into the control group,the experiment group 1 and the experiment group 2,with 20 rats in each group.The control group only underwent laparotomy,cecal free and laparotomy,a rat model of sepsis was established in the experiment group 1 by cecal ligation and perforation(CLP),the experimental group 2 was given intraperitoneal injection of 120 mg/kg 4-PBA,followed immediately by CLP to establish a rat model of peritonitis sepsis.The intestinal tissue,pulmonary and renal vascular permeability,indexes of ERS marker protein(glucose regulatory protein 78,GRP78),CCAAT/enhancer binding protein homologous protein(CHOP),cysteinyl aspartate specific proteinase-12(caspase-12),glucose regulatory protein 94[GRP94],inflammatory factors(interleukin-6[IL-6],interleukin-1β[IL-1β],tumor necrosis factor-α[TNF-α]),apoptosis index,nuclear factor-κB(NF-κB),homocysteine(Hcy),and apoptosis of aortic smooth muscle cells,intestinal function indicators(D-lactate,endotoxin[ET]),renal function indicators(blood urea nitrogen[BUN],retinol-binding protein[RBP],serum creatinine[SCr]andβ2-microglobulin[β2-MG])were compared among the three groups.Results The intestinal tissue,pulmonary and renal vascular permeability,apoptosis index,and GRP78,CHOP,caspase-12,GRP94,IL-6,IL-1β,TNF-α,NF-κB,Hcy,D-lactate,ET,BUN,RBP,SCr andβ2-MG levels in the experiment group 1 were higher than those in the experimental group 2 and the control group,and the differences were statistically significant(P<0.05).The intestinal tissue,pulmonary and renal vascular permeability,CHOP,caspase-12,IL-6,IL-1β,TNF-α,apoptosis index,NF-κB,Hcy,D-lactate,ET,BUN,RBP andβ2-MG in the experimental group 2 were higher than those in the control group,and the differences were statistically significant(P<0.05).Conclusion 4-PBA can improve endoplasmi

关 键 词：4-苯基丁酸 内质网应激 脓毒症 大鼠 

分 类 号：R73[医药卫生—肿瘤]