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作 者:王维[1] 穆宝龙 张文双[1] 吴清雷 张慧慧 曹智丽[1] WANG Wei;MU Baolong;ZHANG Wenshuang;WU Qinglei;ZHANG Huihui;CAO Zhili(Department of Infectious Diseases,Affiliated Second Hospital of Hebei North University,Zhangjiakou 075000,China;Department of Nephrology,Affiliated Second Hospital of Hebei North University,Zhangjiakou 075000,China)
机构地区:[1]河北北方学院附属第二医院感染疾病科,河北张家口075000 [2]河北北方学院附属第二医院肾内科,河北张家口075000
出 处:《基础医学与临床》2024年第11期1551-1556,共6页Basic and Clinical Medicine
基 金:河北省2024年度医学科学研究课题计划(20241127)。
摘 要:目的探讨高良姜素(Gal)对乙型病毒性肝炎(乙肝)大鼠炎性反应的影响。方法大鼠随机分为对照组、乙肝组[尾静脉注射乙型肝炎病毒(HBV)]、Gal低(Gal-L)和高剂量(Gal-H)组、阳性药拉米夫定组、Gal-H+AMPK抑制剂(compound C)组,每组12只。造模后进行药物处理,给药1次/d,持续8周。检测血清中谷丙转氨酶(ALT)、总胆红素(TBIL)、谷草转氨酶(AST)水平;HE染色检测肝组织病理变化;TUNEL染色检测细胞凋亡;染色质免疫共沉淀检测HBV病毒载量;ELISA检测肝组织中单核细胞趋化蛋白-1(MCP-1)、白细胞介素(IL-12)、肿瘤坏死因子-α(TNF-α)水平;Western blot检测天冬氨酸特异性半胱氨酸蛋白酶-3(caspase-3)、Bcl-2相关X蛋白(Bax)、p-AMPK、SIRT1蛋白表达。结果与乙肝组比较,Gal-L组、Gal-H组、拉米夫定组肝脏损伤减轻,血清中AST、TBIL、ALT水平降低,肝组织中细胞凋亡率、HBV病毒载量、MCP-1、IL-12、TNF-α水平及caspase-3、Bax蛋白降低,p-AMPK、SIRT1蛋白升高(P<0.05);Compound C减弱了高剂量Gal对乙肝大鼠肝组织中炎性反应、细胞凋亡及HBV病毒载量的抑制作用。结论Gal抑制乙肝大鼠炎性反应的机制可能与上调AMPK/SIRT1通路有关。Objective To explore the effect of galangin(Gal)on inflammation in hepatitis B rats.Methods The rats were randomly divided into control group,hepatitis B group,Gal-L and Gal-H groups,positive drug lamivudine group and Gal-H+AMPK inhibitor(compound C)group with 12 in each.After modeling,medication treatment was performed once a day for 8 weeks.The level of alanine aminotransferase(ALT),total bilirubin(TBIL)and aspartate aminotransferase(AST)in the serum of rats were detected.HE staining microscopy was applied to detect pathological changes in liver tissue.TUNEL staining microscopy was applied to detect cell apoptosis in liver tissue.Chromatin immuno-precipitation was applied to detect HBV viral load in liver tissue.ELISA was applied to detect the levels of monocyte chemotactic protein-1(MCP-1),interleukin-12(IL-12),and tumor necrosis factor-α(TNF-α)in liver tissue.Western blot was applied to detect the expression of caspase-3,Bcl-2 associated X protein(Bax),p-AMPK and SIRT1 proteins in liver tissue.Results Compared with hepatitis B group,the liver damage of rats in the Gal-L group,Gal-H group and lamivudine group was alleviated;The level of serum AST,TBIL,and ALT,apoptosis rate,HBV viral load and the level of MCP-1,IL-12,TNF-α as well as the expression of caspase-3 and Bax proteins in liver tissue were all reduced.The expression of p-AMPK and SIRT1 proteins in liver tissue increased(P<0.05).Compound C baffled inhibitory effects of high-dose Gal on inflammation,cell apoptosis,and HBV viral load in liver tissue of hepatitis B rats.Conclusions The mechanism of Gal in inhibiting inflammation,cell apoptosis and HBV virus replication in hepatitis B rats is potentially attributed to up-regulation of the AMPK/SIRT1 pathway.
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