4-苯基丁酸对创伤性失血休克大鼠肝损伤的保护作用  

Protective effect of 4-phenylbutyric acid on liver injury in rats with traumatic hemorrhagic shock

作　　者：厉冰[1] 尚华[2] 梅孝臣 门中俊 翟润 任武[3] 孙万日[1] Li Bing;Shang Hua;Mei Xiaochen;Men Zhongjun;Zhai Run;Ren Wu;Sun Wanri(Department of General Surgery,Nanyang Central Hospital/Department of General Surgery,Nanyang Central Hospital Affiliated to Henan University,Nanyang 473000,China;Nanyang Central Hospital,Department of Pediatric Digestive and Cardiovascular Surgery/Department of Pediatric Digestive and Cardiovascular Surgery,Nanyang Central Hospital Affiliated to Henan University,Nanyang 473000,China;Department of General Surgery,Henan Cancer Hospital,Zhengzhou 453000,China)

机构地区：[1]南阳市中心医院普外科,河南大学附属南阳市中心医院普外科,473000 [2]南阳市中心医院儿童消化心血管科,河南大学附属南阳市中心医院儿童消化心血管科,473000 [3]河南省肿瘤医院普外科,郑州453000

出　　处：《中华实验外科杂志》2021年第8期1499-1502,共4页Chinese Journal of Experimental Surgery

摘　　要：目的观察4-苯基丁酸(PBA)对创伤性失血休克大鼠肝损伤的保护作用。方法将60只SD大鼠随机数字表法分为假手术组、模型组和4-PBA组,每组20只,模型组和4-PBA组采用左下肢、胫骨骨折和股部软组织损伤并失血方法制备大鼠创伤性失血休克模型,假手术组仅行麻醉、结扎血管,不进行创伤失血。4-PBA组大鼠每天灌胃4-PBA 0.5 g/kg,假手术组和模型组灌胃等体积生理盐水。3组大鼠治疗72 h后,观察3组大鼠死亡率;采用苏木精-伊红(HE)染色分析肝脏病理变化;采用自动生化仪检测肝功能生化指标;采用分光光度法测定3组大鼠肝脏丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)水平;采用蛋白质印迹法(Western blot)分析3组大鼠内质网应激蛋白表达水平;组间比较采用方差分析。结果4-PBA组大鼠血清丙氨酸转氨酶(ALT)和谷草转氨酶(AST)水平[(187.24±31.09)、(364.17±28.98)U/L]明显低于模型组[(367.12±44.19)、(872.34±30.41)U/L],差异有统计学意义(t=7.130、6.091,P<0.05)。4-PBA组大鼠肝组织中SOD活性和GSH水平[(30.17±5.41)U/mg、(783.22±25.21)mg/g]高于模型组[(19.30±4.81)U/mg、(551.28±19.38)mg/g],差异有统计学意义(t=5.901、3.226,P<0.05)。4-PBA组大鼠肝组织MDA和GSH水平[(4.11±0.38)nmol/mg]低于模型组[(7.02±0.59)nmol/mg],差异有统计学意义(t=4.109,P<0.05)。4-PBA组大鼠肝组织葡萄糖调节蛋白78(GRP78)、C/EBP同源蛋白(CHOP)、生长阻滞和DNA损伤诱导基因153(GADD153)蛋白表达水平(1.63±0.22、1.99±0.28、1.53±0.20)低于模型组(2.31±0.23、3.09±0.31、2.89±0.27),差异有统计学意义(t=3.287、2.943、3.810,P<0.05)。4-PBA组大鼠肝组织凋亡比例[(8.12±0.28)%]低于模型组[(15.32±3.98)%],差异有统计学意义(t=3.109,P<0.05)。结论4-PBA可显著减轻创伤性失血休克大鼠肝损伤,与其抑制内质网应激和脂质过氧化反应相关。Objective To study the protective effect of 4-phenylbutyric acid(PBA)on liver injury in rats with traumatic hemorrhagic shock.Methods Totally,60 SD rats were randomly divided into sham operation group,model group and PBA group by random number table,20 mice/group.The model group and PBA group were treated with left lower extremity,tibia fracture and soft tissue injury of femoral and blood loss method was used to prepare the model of traumatic blood loss shock in rats.The rats in sham operation group were only anesthetized and given ligation of blood vessels,without blood loss.Rats in PBA group were given 4-PBA 0.5 g/kg daily,and the sham operation group and model group were given normal saline.After 72 h of treatment,the pathological changes of liver were analyzed by hematoxylin and eosin(HE)staining.The biochemical indexes of liver function were detected by automatic biochemical instrument.The levels of malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in the liver of three groups were determined by spectrophotometry.The expression of stress protein in the endoplasmic reticulum of three groups of rats was analyzed by Western blotting.SPSS 17.0 statistical software was used to analyze the mean value of normal distribution±standard deviation.Results Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels in 4-PBA group[(187.24±31.09),(172.34±30.41)U/L]were significantly lower than those in the model group[(367.12±44.19),(364.17±28.98)U/L](t=7.130,6.091,P<0.05).SOD activity and GSH level in liver tissues of 4-PBA group[(30.17±5.41)U/mg,(783.22±25.21)mg/g]were significantly increased as compared with those in the model group[(19.30±4.81)U/mg,(551.28±19.38)mg/g](t=5.901,3.226,P<0.05).The expression levels of glucose regulated protein 78(GRP78),C/EBP homologous protein(CHOP)and growth-arrest and DNA damage-inducible gene 153(GADD153)in liver tissues of 4-PBA group(1.63±0.22,1.99±0.28,1.53±0.20)were significantly lower than those in the model group(2.31±0.23,3.09±0.31,2.89±

关 键 词：4-苯基丁酸 失血性休克 肝损伤 炎性反应 氧化应激 

分 类 号：R965[医药卫生—药理学]