首页|白桦脂酸对CCl4诱导小鼠急性肝损伤的保护作用及机制研究

白桦脂酸对CCl4诱导小鼠急性肝损伤的保护作用及机制研究

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目的 研究白桦脂酸(Betulinic acid)对四氯化碳(CCl4)诱导的小鼠肝损伤的保护作用及其相关机制.方法 50只 ICR小鼠随机分为5组:空白对照组、CCl4组、CCl4+水飞蓟素组(200 mg/kg)、CCl4+白桦脂酸低剂量组(20 mg/kg)、CCl4+白桦脂酸高剂量组(40 mg/kg).除空白对照组和CCl4组给予等体积蒸馏水外,其余各组每日灌胃给予相应剂量药物,共7 d.末次给药2 h后,腹腔注射0.1%的CCl4植物油溶液(10 mL/kg),空白对照组腹腔注射等体积植物油.18 h后取血、肝脏.各组小鼠肝脏做 HE染色,检测血清丙二醛(MDA)、超氧化物歧化酶(SOD)、白介素(IL-6、IL-1β)和肿瘤坏死因子(TNF-α)水平,并采用蛋白免疫印记法(Western blot)检测肝脏组织中 p-NF-κB、NF-κB、p-IκBα、IκBα、Nrf-2和 HO-1蛋白表达.结果 白桦脂酸(20、40 mg/kg)能降低CCl4诱导的肝损伤小鼠血清 MDA、IL-6、IL-1β和 TNF-α含量(P<0.01),升高 SOD含量(P<0.01);能显著改善小鼠肝脏组织的病理学改变;显著降低肝脏 p-NF-κB、p-IκBα蛋白表达(P<0.01),增加肝脏 Nrf-2和 HO-1蛋白表达(P<0.05~0.01).结论 白桦脂酸对CCl4诱导的小鼠肝损伤具有保护作用,这种效应可能与 Nrf-2/HO-1/NF-κB信号通路有关.
The Protective Effect of Betulinicd Acid Alleviates CCl4-Induced Acute Liver Injury in Mice and Its Related Mechanism
OBJECTIVE To observe the effect of betulinic acid on CCl4induced liver injury in mice and its possible molecular mechanisms.METHODS Male ICR mice were randomly divided into 5 groups:normal control group,CCl4group(20 mg/kg),CCl4+Silibinin group(200 mg/kg),CCl4+betulinic acid group(20 mg/kg),CCl4+betulinic acid group(40 mg/kg). Mice in the normal control group and CCl4group were given distilled water while other groups were given drugs in 7 days by ga-vage.2 h after the last administration,0.1% CCl4with vegetable oil solution(10 mL/kg)by intraperitoneal injection,and the mice in normal control group were given the same volume of vegetable oil solution.18 h after the model establishment,the blood and liver were collected.Hematoxylin(HE)staining was used to observe the changes of hepatic histopathology.Super-oxide dismutase(SOD),malonaldehyde(MDA),interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor(TNF-α)were measured by corresponding kits.Western blot was used to demonstrate the expression levels of related protein.RE-SULTS Betulinic acid significantly reduced levels of pro-inflammatory cytokines including interleukin-6(IL-6),interleukin-1β (IL-1β)and tumor necrosis factor-α(TNF-α)in serum.Besides,it also attenuated superoxide dismutase(SOD)and malondi-aldehyde(MDA)in serum.In addition,betulinic acid regulated proteins levels of Nrf-2/HO-1/NF-κB pathway in liver.CON-CLUSION Betulinic acid exhibited therapeutical effect on CCl4induced liver injury in mice which might be related to the regula-tion of Nrf-2/HO-1/NF-κB pathway.

betulinic acidliver injuryNrf-2/HO-1/NF-κB

徐立新、严丽军

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南通市第三人民医院肝病科,江苏 南通 226000

南京医科大学第一临床医学院,江苏 南京 226000

白桦脂酸 肝损伤 Nrf-2/HO-1/NF-κB

国家自然科学基金

81774364

2017

南京中医药大学学报
南京中医药大学

南京中医药大学学报

CSTPCDCSCD北大核心
影响因子:1.658
ISSN:1672-0482
年,卷(期):2017.33(6)
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