摘要
目的:探讨姜黄素(CUR)对脂多糖(LPS)/D-氨基半乳糖(D-GalN)联合注射诱导大鼠急性肝损伤(AHI)后肝细胞自噬的影响。方法:雄性SD大鼠随机分为对照组、AHI组、CUR组、自噬抑制剂3-甲基腺嘌呤(3-MA)组和3-MA+CUR组,每组6只。采用腹腔注射LPS及D-GalN制造急性肝损伤动物模型,在肝损模型建立后12 h检测各组大鼠肝功能,HE染色观察肝组织病理变化,透射电镜观察自噬体形成情况,Western blot法检测肝组织自噬相关蛋白LC3和beclin 1的表达,酶联免疫吸附实验检测血清TNF-α含量。结果:与对照组相比,AHI组大鼠的血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平显著升高(P<0.05),肝组织病理损伤程度加重,血清TNF-α含量增加(P<0.01),自噬体数量增多,自噬相关蛋白LC3和beclin 1的表达均升高(P<0.01);与AHI组相比,姜黄素组大鼠的血清ALT和AST水平明显降低(P<0.05),肝组织病理损伤情况明显改善,血清TNF-α含量明显减少(P<0.01),自噬体明显增多,自噬相关蛋白LC3和beclin 1的表达明显增加(P<0.01);而与姜黄素组相比,3-MA组及3-MA+CUR组的血清ALT和AST水平升高(P<0.05),肝组织损伤加重,血清TNF-α含量增加(P<0.01),自噬体明显减少,自噬相关蛋白LC3和beclin 1表达显著减少(P<0.01)。结论:姜黄素可能通过激活肝细胞自噬从而减轻LPS/D-GalN诱导的大鼠急性肝损伤。
AIM:To investigate the effect of curcumin(CUR)on autophagy of hepatovyte in rats with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)-induced acute liver injury(AHI).METHODS:The healthy male Sprague-Dawley(SD)rats were randomized into the control group,AHI group,CUR group,3-methy-ladenine(3-MA)group and 3-MA+CUR group,with 6 rats in each group.AHI was induced with an intraperitoneal injection of LPS and DGalN.Liver function was tested 12 h after LPS/D-GalN treatment.Pathological changes of liver tissues were analyzed by HE staining.The amount of autophagic bodies were observed by transmission electron microscopy.The protein levels of autophagy related-proteins LC3 and beclin 1 in livers were detected by Western blot.ELISA were used to examine the serum levels of tumor necrosis factor-α(TNF-α).RESULTS:Compared with control group,the serum level of alanine aminotransferase(ALT)and asparated aminotransferase(AST)were significantly increased,hepatic pathological damage were aggravated and serum TNF-α level was significantly increased in AHI group,while the autophagic bodies and the protein levels of LC3 and beclin 1 were increased(P<0.01).Compared with AHI group,the serum level of ALT and AST were significantly decreased,hepatic pathological damage were attenuated and serum TNF-α level was significantly reduced(P<0.05),while the autophagic bodies and the protein levels of LC3 and beclin 1 were significantly increased in CUR group(P<0.01).Compared with CUR group,the serum level of ALT and AST were significantly increased,hepatic pathological damage were aggravated and serum level of TNF-α was significantly increased in 3-MA group and 3-MA+CUR group,while the autophagic bodies and the protein levels of LC3 and beclin 1 were decreased(P<0.01).CONCLUSION:Curcumin protects rats against LPS/D-GalN-induced liver injury,partially due to activation of hepatocyte autophagy in livers.
作者
谢一潋
杨乃彬
王丽萍
宣艳艳
邬怡怡
钱国清
石洁君
史光侠
李国祥
XIE Yi-lian;YANG Nai-bing;WANG Li-ping;XUAN Yan-yan;WU Yi-yi;QIAN Guoqing;SHI Jie-jun;SHI Guang-xia;LI Guo-xiang(Department of Infectious Disease,Ningbo First Hospital,Ningbo 315000,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2020年第5期860-864,共5页
Chinese Journal of Pathophysiology
基金
浙江省中医药科技计划项目(No.2018ZB115)
浙江省医药卫生科技计划项目(No.2018KY682)。
关键词
姜黄素
自噬
急性肝损伤
Curcumin
Autophagy
Acute hepatic injury
