姜黄素对脂多糖/D-氨基半乳糖诱导大鼠急性肝损伤中内质网应激的影响  

Effect of curcumin on lipopolysaccharide/D-galactosamine-induced acute liver injury in rats

作　　者：谢一潋[1] 褚金国[2] 杨乃彬 王丽萍[1] 吴春央 李国祥[1] XIE Yilian;CHU Jinguo;YANG Naibing;WANG Liping;WU Chunyang;LI Guoxiang(Department of Infectious Diseases,Ningbo First Hospital,Ningbo 315000,China)

机构地区：[1]宁波市第一医院感染科,315000 [2]宁波市第一医院全科,315000

出　　处：《浙江医学》2020年第13期1359-1363,I0004,共6页Zhejiang Medical Journal

基　　金：浙江省医药卫生科技计划项目(2018KY682);浙江省中医药科技计划项目(2018ZB115)。

摘　　要：目的探讨姜黄素预给药对脂多糖/D-氨基半乳糖(D-GalN)诱导大鼠急性肝损伤中内质网应激(ERS)的影响。方法30只雄性SD大鼠按随机数字表法分为正常对照组、肝损组、姜黄素组,每组10只。在造模前5 d,姜黄素组按5 ml/kg灌饲姜黄素溶液(姜黄素溶于0.5%羧甲基纤维素钠中),正常对照组、肝损组按5 ml/kg灌饲0.5%羧甲基纤维素钠溶液,1次/d,连续5 d。肝损组、姜黄素组采取腹腔注射含脂多糖(8μg/kg)+D-GalN(800 mg/kg)的0.9%氯化钠注射液800μl制作急性肝损伤动物模型,正常对照组大鼠腹腔注射800μl 0.9%氯化钠注射液;模型建立12 h后处死大鼠并收集血清及肝组织,检测并比较3组大鼠血清肝功能指标、丙二醛(MDA)、超氧化物歧化酶(SOD)水平,HE染色观察肝组织病理学变化,TUNEL染色观察肝细胞凋亡情况,Western blot法检测肝组织内ERS相关蛋白葡萄糖调节蛋白78(GRP78)、C/EBP同源蛋白(CHOP)表达量。结果正常对照组大鼠肝组织未见明显病变;肝损组大鼠部分肝细胞坏死,坏死的肝细胞核碎裂、胞质深染,坏死区可见较多炎细胞浸润;姜黄素组大鼠肝组织内坏死细胞较肝损组明显减少。与正常对照组比较,肝损组大鼠血清ALT、AST、MDA水平,肝细胞凋亡指数,GRP78、CHOP蛋白表达水平均明显升高(均P<0.05),SOD水平明显降低(P<0.05);姜黄素组大鼠血清ALT、AST、MDA水平,肝细胞凋亡指数,CHOP蛋白表达水平也明显升高(均P<0.05),SOD水平、GRP78蛋白表达水平比较差异均无统计学意义(均P>0.05)。与肝损组比较,姜黄素组大鼠血清ALT、AST、MDA水平,肝细胞凋亡指数,GRP78、CHOP蛋白表达水平均明显降低(均P<0.05),SOD水平明显升高(P<0.05)。结论姜黄素可能通过抑制ERS反应对脂多糖/D-GalN诱导大鼠的急性肝损伤起保护作用。Objective To investigate the effect of curcumin on lipopolysaccharide(LPS)/D-galactosamine(D-GalN)-induced acute liver injury in rats.Methods Thirty male SD rats were randomly divided into control group,liver injury group and curcumin group with 10 rats in each group.Liver injury was induced by intraperitoneal injection of LPS/D-GalN in liver injury group and curcumin group.The curcumin solution was prepared by dissolving 120 curcumin in 5 ml 0.5%sodium carboxymethyl cellulose solution,rats in curcumin group were fed with curcumin solution 5 ml/kg,while rats in control group and liver injury group were fed with 0.5%sodium carboxymethyl cellulose solution for 5 days before the modeling.The rats were sacrificed 12 h after modeling and serum and liver tissue samples were collected.Serum liver function indexes,MDA and SOD levels were detected and compared among the three groups.HE staining was used to observe the pathological changes of liver tissue.TUNEL staining was used to observe the apoptosis of hepatocytes.Western blot was used to detect the expression of endoplasmic reticulum stress(ERS)related proteins,glucose regulated protein 78(GRP78)and C/EBP homologous protein(CHOP).Results In control group,no significant pathological changes in the liver tissuewere found.In liver injury group,the hepatocytes were necrotic and the nucleus of the necrotic liver was fragmented.The cytoplasm was deeply stainedand more inflammatory cells were infiltrated in the necrotic area.The number of necrotic cells in curcumin group were significantly less than that in the liver injury group.Compared with control group,serum ALT,AST,MDA levels,hepatocyte apoptosis index,GRP78 and CHOP protein expression levels were significantly increased(P<0.05),while SOD levels were significantly decreased in liver injury group(P<0.05).Serum ALT,AST,MDA levels,hepatocyte apoptosis index and CHOP protein expression level were also significantly increased in curcumin group(all P<0.05),while SOD level and GRP78 protein expression level were not significa

关 键 词：姜黄素 肝损伤 内质网应激 脂多糖 D-氨基半乳糖 

分 类 号：R285.5[医药卫生—中药学]