桂皮醛对百草枯中毒小鼠急性肝损伤的保护作用  

Protective effects of cinnamaldehyde on paraquat-induced liver injury in mice

作　　者：郭治华[1] 刘振宁[1] 李子英[2] 蒲羿 韩思盈 Guo Zhi-hua;Liu Zhen-ning;Li Zi-ying;Pu Yi;Han Si-ying(Emergency Department,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院急诊科,辽宁沈阳110004 [2]中国医科大学附属盛京医院实验研究中心,辽宁沈阳110004

出　　处：《中国急救医学》2022年第9期779-784,共6页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金(82072157);沈阳市中青年科技创新人才计划(RC200291)。

摘　　要：目的探讨桂皮醛对百草枯中毒小鼠急性肝损伤的保护作用机制。方法将C57BL/6N小鼠共计24只随机平均分成4组,每组6只。百草枯中毒组:按照30 mg/kg剂量百草枯腹腔注射;低剂量和高剂量桂皮醛干预组:按照50 mg/(kg·d)或100 mg/(kg·d)两种不同剂量桂皮醛进行小鼠灌胃7 d,然后给予百草枯30 mg/kg腹腔注射;对照组:0.3 mL生理盐水灌胃。在腹腔注射百草枯后24 h时,收集小鼠血液和肝组织标本。采用ELISA方法检测小鼠血清中白细胞介素-1β(IL-1β)含量,采用生化法检测肝组织中丙二醛(MDA)和超氧化物歧化酶(SOD)含量,肝组织HE染色观察形态学变化,利用免疫组化或Western blot方法检测肝组织中沉默调节蛋白1(SIRT1),过氧化物酶体增殖物激活受体-γ共激活因子-1α(PGC-1α),NACHT、LRR和PYD结构域蛋白3(NLRP3)和半胱氨酸蛋白酶-1(Caspase-1)蛋白表达水平。结果与对照组比较,百草枯中毒小鼠肝组织结构破坏,炎性细胞浸润,组织学评分增加(分:0.33±0.21 vs.5.83±0.31,P<0.05);SOD含量减少(U/mg:388.18±22.89 vs.95.57±29.36,P<0.05),MDA含量增加(nmol/mg:2.78±0.52 vs.8.72±1.01,P<0.05),血清炎性细胞因子IL-1β含量增加(ng/L:16.88±5.70 vs.64.81±5.98,P<0.05)。与百草枯中毒组比较,两组桂皮醛干预组肝组织学评分改善(分:5.83±0.31 vs.4.33±0.21 vs.3.50±0.43,P<0.05),SOD含量增加(U/mg:95.57±29.36 vs.138.55±24.72 vs.209.76±27.92,P<0.05),MDA含量减少(nmol/mg:8.72±1.01 vs.7.26±0.52 vs.6.15±0.61,P<0.05),血清炎性细胞因子IL-1β含量减少(ng/L:64.81±5.98 vs.49.68±6.04 vs.40.75±4.44,P<0.05)。桂皮醛上调肝组织中SIRT1和PGC-1α表达,降低NLRP3和Caspase-1蛋白表达(P<0.05)。结论桂皮醛可能通过促进SIRT1/PGC-1α表达和抑制NLRP3/Caspase-1表达发挥抗氧化和抗炎作用,对百草枯中毒小鼠急性肝损伤产生保护作用。Objective To study the protective effects of cinnamaldehyde on acute liver injury induced by paraquat(PQ).Methods C57BL/6N mice(n=24)were randomly divided into 4 groups,paraquat-poisoned group(PQ group):paraquat was intraperitoneally administered at the dose of 30 mg/kg;low-dose cinnamaldehyde pretreatment group(L-CA group):cinnamaldehyde was intragastrically pretreated for consecutive 7 days at the dose of 50 mg/(kg·d)before paraquat(30 mg/kg)was injected intraperitoneally;high-dose cinnamaldehyde pretreatment group(H-CA group):cinnamaldehyde was intragastrically pretreated for consecutive 7 days at the dose of 100 mg/(kg·d)before paraquat(30 mg/kg)was injected intraperitoneally;control group:0.3 mL saline was intragastrically administered.Liver and blood tissue samples were collected at 24 h after intraperitoneal injection of paraquat.The IL-1βlevels in serum were measured by ELISA assays;the contents of superoxide dismutase(SOD)and malondialdehyde(MDA)in liver tissue were detected by biochemical method;the pathological change and liver injury scores were evaluated;the protein expression of silent information regulator 1(SIRT1),peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α),NLRP3,and Caspase-1 was determined by immunohistochemistry or Western blot.Results Compared with the control group,the damage of liver tissue structure,infiltration of inflammatory cells,the histological scores increased(scores:0.33±0.21 vs.5.83±0.31),the SOD contents in hepatic tissue reduced(U/mg:388.18±22.89 vs.95.57±29.36),and the MDA content in hepatic tissue(nmol/mg:2.78±0.52 vs.8.72±1.01)and IL-1βlevels in serum(ng/L:16.88±5.70 vs.64.81±5.98)increased in PQ group(all P<0.05).Compared with the PQ group,the pretreatment of cinnamaldehyde greatly improved the histological scores(scores:5.83±0.31 vs.L-CA:4.33±0.21 vs.H-CA:3.50±0.43),the SOD contents in hepatic tissue increased(U/mg:95.57±29.36 vs.L-CA:138.55±24.72 vs.H-CA:209.76±27.92),and the MDA content in hepatic tissue(nmol/mg:8.72±1.01 vs.L-C

关 键 词：百草枯中毒 急性肝损伤 桂皮醛 过氧化物酶体增殖物激活受体-γ共激活因子-1α(PGC-1α) 沉默调节蛋白1(SIRT1) NACHT、LRR和PYD结构域蛋白3(NLRP3) 

分 类 号：R285.5[医药卫生—中药学]