小檗碱预处理对大鼠肝脏移植诱发肝损伤的影响分析  

Effect of berberine preconditioning on liver injury induced by liver transplantation in rats

作　　者：刘文娜[1] 霍明霞 田立东[1] 张广华[1] Liu Wenna;Huo Mingxia;Tian Lidong;Zhang Guanghua(Department of Anesthesiology,Chu Hsien-I Memorial Hospital&Tianjin Institute of Endocrinology,Tianjin Medical University,NHC Key Laboratory of Hormones and Development,Tianjin Key Laboratory of Metabolic Diseases,Tianjin 300134,China)

机构地区：[1]天津医科大学朱宪彝纪念医院麻醉科,天津市内分泌研究所,国家卫健委激素与发育重点实验室,天津市代谢性疾病重点实验室,天津300134

出　　处：《实用器官移植电子杂志》2024年第4期320-324,共5页Practical Journal of Organ Transplantation(Electronic Version)

基　　金：天津市教委科研计划项目(2020KJ192);天津市医学重点学科(专科)建设项目(TJYXZDXK-032A)。

摘　　要：目的探讨小檗碱预处理在大鼠自体原位肝移植术诱发肝脏损伤的保护作用及相关的机制。方法健康雄性清洁级SD大鼠24只,体重为250~280 g,分为3组(n=8):假手术组(S组)、模型组(AT组)和小檗碱预处理组(B组)。S组仅进行开腹,游离肝脏周围的血管和韧带,关腹。AT组和B组均制备自体原位肝移植诱发肝脏损伤大鼠模型,B组术前1周灌胃小檗碱[200 mg/(kg·d)]。在灌注6 h时麻醉大鼠,取其血清和肝脏组织,检测血清丙氨酸转氨酶(alanine transaminase,ALT)和天冬氨酸转氨酶(aspartate transaminase,AST)水平,采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法测定血清高迁移率族蛋白B-1(high mobility group box-1 protein,HMGB-1)含量,采用免疫组织化学法测定肝脏组织过氧化物酶体增殖物激活受体γ(peroxisome proliferators-activated receptorsγ,PPARγ)和核转录因子-κB(nuclear transcription factor-κB,NF-κB)表达,采用蛋白免疫印迹法检测凋亡相关斑点样蛋白(apoptosis associated spot-like protein,ASC)、NLRP3和Pro-caspase1蛋白表达。结果与S组比较,AT组血清ALT、AST水平和HMGB1含量升高。肝脏组织PPARγ表达下调,NF-κB、ASC、NLRP3和Pro-caspase1表达上调(P<0.05),肝脏组织病理学损伤明显加重。与AT组比较,B组血清ALT、AST水平和HMGB1含量降低,肝脏组织PPARγ表达上调,NF-κB、ASC、NLRP3和Pro-caspase1表达下调(P<0.05),肝脏组织病理学损伤明显改善。结论预处理小檗碱可以通过激活PPARγ,抑制NF-κB表达,进而抑制细胞焦亡通路,从而发挥对大鼠肝脏移植过程诱发肝损伤的保护作用。Objective To investigate the protective effect of berberine pretreatment on liver injury in rats undergoing autogenous orthotopic liver transplantation and its related mechanism.Methods Twenty-four cleangrade healthy male Sprague-Dawley rats were divided into 3 groups(n=8).They were sham operation group(S group),model group(AT group)and berberine pretreatment group(B group).The weight was 250~280 g.In S group,the abdomen was opened,the corresponding blood vessels and ligaments were isolated,and the abdomen was closed.Rat models of liver injury after orthotopic liver transplantation were prepared in both AT and B groups,and berberine〔200 mg/(kg·d)〕was given by gavage 1 week before surgery in B group.Rats were anesthetized at 6 h after reperfusion,and the serum and liver tissues were collected.The serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected,the contents of serum high mobility group box-1 protein(HMGB1)(by enzyme-linked immunosorbent assay),and the expression of peroxisome proliferator activated receptor(PPARγ)and nuclear transcription factor-κB(NF-κB)(by immunohistochemistry)were determined.The expressions of ASC,NLRP3 and Pro-caspase1(by Western blot)were detected.Results Compared with S group,the levels of serum ALT and AST and the contents of HMGB1 were significantly increased.The expression of PPARγin liver was down-regulated and the expression NF-κB、ASC、NLRP3 and Pro-caspase1 in liver was up-regulated,and histopathological injury of liver was significantly aggravated in AT and B groups(P<0.05).Compared with AT group,the levels of serum ALT and AST and the contents of HMGB1 were significantly decreased.The expression of PPARγin liver was up-regulated and the expression NF-κB、ASC、NLRP3 and Pro-caspase1 in liver was down-regulated in liver tissue(P<0.05),and liver histopathological damage was significantly improved in B group.Conclusion Pretreatment of berberine can inhibit the expression of NF-κB by activating PPARγand then inhibiting the py

关 键 词：肝移植 肝脏损伤 小檗碱 过氧化物酶体增殖物激活受体Γ 核转录因子-ΚB 细胞焦亡 

分 类 号：R657.3[医药卫生—外科学]