尿石素A预处理对肝缺血再灌注损伤大鼠模型的保护作用  

Protective effect of urolithin A pretreatment in a rat model of hepatic ischemia-reperfusion injury

作　　者：米凯 黄锐[2] MI Kai;HUANG Rui(Department of General Surgery,The Second Affiliated Hospital of Chengdu Medical College&Nuclear Industry 416 Hospital,Chengdu 610500,China;Department of Hepatobiliary Surgery,Sichuan Provincial People’s Hospital,Chengdu 610007,China)

机构地区：[1]核工业四一六医院(成都医学院第二附属医院)普外科,成都610500 [2]四川省人民医院肝胆外科,成都610007

出　　处：《临床肝胆病杂志》2020年第8期1783-1787,共5页Journal of Clinical Hepatology

基　　金：国家自然科学基金项目(81302161);四川省卫生与计划生育委员会课题(17PJ587)。

摘　　要：目的探讨尿石素A(Uro-A)对肝缺血再灌注损伤(HIRI)大鼠模型的保护作用。方法将40只SD大鼠随机分为假手术组、模型组、Uro-A低剂量组(1 mg/kg)和Uro-A高剂量组(3 mg/kg),每组10只。造模前Uro-A低剂量和高剂量组每天灌胃药物1次,持续5 d。动物麻醉后造模,恢复血流后6 h检测血清中ALT、AST与乳酸脱氢酶(LDH)的含量,ELISA法检测肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、IL-1β、IL-6和TNFα含量,观察肝脏病理损伤与肝细胞凋亡情况,Western Blot法检测肝脏中内质网分子伴侣葡萄糖调节蛋白78(GRP78)、下游应激转录因子(CHOP)和凋亡蛋白家族(Caspase-12)的表达水平。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果Uro-A高剂量组ALT、AST、LDH、MDA、CAT、IL-1β、IL-6、TNFα、CHOP、GRP78、Caspase-12水平及凋亡率均较模型组降低,SOD含量较模型组升高,差异均有统计学意义(P值均<0.05)。模型组肝脏结构破坏严重,阳性率90%,Uro-A高剂量组肝脏结构完好,未见明显组织增生与炎性细胞增多,阴性率80%。与Uro-A高剂量组相比,Uro-A低剂量组ALT、AST、LDH水平和细胞凋亡率均显著升高(P值均<0.05)。结论Uro-A预处理可降低大鼠肝脏缺血再灌注造成的损伤,减少氧化损伤与炎症因子的释放,其机制与通过抑制内质网应激通路减少肝细胞的凋亡有关。Objective To investigate the protective effect of urolithin A(Uro-A)against hepatic ischemia-reperfusion injury(HIRI)in rats.Methods A total of 40 Sprague-Dawley rats were randomly divided into sham-operation group,model group,low-dose Uro-A(1 mg/kg)group,and high-dose Uro-A(3 mg/kg)group,with 10 rats in each group.Before modeling,the rats in the low-and high-dose Uro-A groups were given the drug by gavage once a day for 5 consecutive days.The model was established after anesthesia,and the serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH)were measured at 6 hours after the recovery of blood flow.ELISA was used to measure the content of superoxide dismutase(SOD),malondialdehyde(MDA),catalase(CAT),interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the liver,and liver pathological injury and hepatocyte apoptosis were evaluated.Western blot was used to measure the expression of the endoplasmic reticulum chaperone glucose-regulated protein 78(GRP78),the downstream transcription factor CHOP,and the apoptosis protein caspase-12 in the liver.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the model group,the high-dose Uro-A group had significantly lower levels of ALT,AST,LDH,MDA,CAT,IL-1β,IL-6,TNF-α,CHOP,GRP78,and caspase-12 and apoptosis rate and a significantly higher content of SOD(all P<0.05).The model group had severe damage of liver structure,with a positive rate of 90%,while the high-dose Uro-A group had intact liver structure without obvious tissue proliferation or inflammatory cell proliferation,with a negative rate of 80%.Compared with the high-dose Uro-A group,the low-dose Uro-A group had significant increases in the levels of ALT,AST,and LDH and apoptosis rate(all P<0.05).Conclusion Uro-A pretreatment can alleviate liver ischemia-reperfusion injury in rat

关 键 词：肝疾病 再灌注损伤 尿石素A 大鼠 Sprague-Dawley 

分 类 号：R575[医药卫生—消化系统]