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沙棘熊果酸对酒精性肝病模型大鼠的保护作用 被引量:6

Protective Effect of Ursolic Acid Extracted from Hippophae rhamnoides L.on Alcohol-Induced Liver Disease in Rats
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摘要 目的探讨沙棘熊果酸对酒精性肝病模型大鼠的保护作用及其机制。方法SPF级雄性Wistar大鼠50只,随机分为5组:正常对照组、模型对照组和熊果酸小、中、大剂量(50,100,150 mg·kg^(-1)·d^(-1))组,每组10只。采用灌胃方式给药,持续8周,末次给药12 h后,腹主动脉取血,留取肝脏组织。测定大鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平及肝匀浆中三酰甘油(TG)含量;苏木精-伊红(HE)染色观察大鼠肝脏形态结构改变;TUNEL法测定大鼠肝细胞凋亡率;免疫印迹法(Western blotting)检测大鼠肝组织Bcl-2、Bax及cleaved caspase-3的蛋白表达变化。结果HE染色显示,模型对照组大鼠肝索排列紊乱,且细胞浆内散在空泡,肝组织内炎症细胞聚集,肝细胞呈现片状坏死。但熊果酸各剂量组较模型对照组肝脏脂肪变性明显改善,炎症细胞浸润及坏死区域明显减少,组织结构趋向正常,且熊果酸中、大剂量组血清ALT、AST水平及肝组织TG含量明显降低(P<0.05)。TUNEL结果显示,熊果酸大剂量组染色阳性细胞数及肝细胞凋亡指数较模型对照组明显降低(P<0.05);免疫印迹法检测结果显示,与模型对照组比较,熊果酸各剂量组肝组织Bcl-2蛋白表达均明显升高,Bax蛋白表达均明显下降,且cleaved caspase-3蛋白表达量均增多。结论沙棘熊果酸对大鼠酒精性肝病有改善作用,其机制可能与调控肝细胞凋亡关键蛋白Bcl-2、Bax、cleaved caspase-3的表达水平,进而抑制肝细胞的异常凋亡有关。 Objective To explore the effect and mechanism of ursolic acid(UA)extracted from Hippophae rhamnoides L.on alcohol-induced liver disease in rats.Methods Fifty male Wistar rats(SPF)were randomly divided into five groups:normal control group,model control group,low-,medium-and high-dose UA group,10 rats in each group.The rats were administered by intragastric administration for eight consecutive weeks.After 12 hours of last administration,blood was collected by abdominal aorta and the liver was obtained for histopathological and biochemical assays.The levels of ALT and AST in serum was detected.The content of TG in liver homogenate was determined.The morphological changes of hepatic tissue in rats were observed by HE staining.The apoptotic rate of rat liver cells was detected by TUNEL method.The protein expressions of Bcl-2,Bax and cleaved caspase-3 in liver tissue were detected by Western blotting.Results In model control group,HE staining showed that the hepatic cord was arranged disorderly,and there were lots of vacuoles in the cytoplasm of hepatocytes.The inflammatory cells in the liver tissue gathered,and the hepatocytes showed flake necrosis in model control group.Compared with model control group,ursolic acid significantly improved the steatosis of the liver.In the UA group,infiltration and necrosis of inflammatory cells were significantly decreased,the tissue structure tended to be normal,and the activity of serum ALT,AST,and the content of TG in the medium-and high-dose UA group liver tissue were significantly decreased(P<0.05).TUNEL results showed that the number of positive cells and the apoptosis index of hepatocytes in the high dose of UA group were significantly lower than in model control group(P<0.05).Western blotting results showed that the protein expression of Bcl-2 in liver tissue of UA groups was significantly increased,the protein expression of Bax was significantly decreased,and the protein expression of cleaved caspase-3 was increased,compared with model control group.Conclusion Ursolic acid
作者 李可欣 张男男 侯瑞丽 张文龙 高龙 苗晓涵 戈娜 LI Kexin;ZHANG Nannan;HOU Ruili;ZHANG Wenlong;GAO Long;MIAO Xiaohan;GE Na(Institute of Nutrition and Food Health,Baotou Medical College,Baotou 014040,China;Department of Orthopedics,the First Affiliated Hospital,Baotou Medical College,Baotou 014010,China)
出处 《医药导报》 CAS 北大核心 2021年第5期616-621,共6页 Herald of Medicine
基金 国家自然科学基金资助项目(81550044,81760586) 内蒙古自治区自然科学基金资助项目(2014MS0303) 2015年度内蒙古自治区高等学校“青年科技英才计划”项目(NJTY-15-B11) 内蒙古自治区卫生计生科研计划项目(201701084) 2017年度内蒙古自治区草原英才工程青年创新人才培养计划项目(Q2017089) 2016年度包头市青年创新人才项目(包人社办字[2017]284号) 内蒙古自治区研究生科研创新项目(S2018112037Z) 内蒙古自治区教育厅项目(NJZY16208) 包头医学院科学研究基金项目(BYJJ-YF-2018010)。
关键词 熊果酸 沙棘 肝病 酒精性 细胞凋亡 Ursolic acid Hippophae rhamnoides L. Liver disease,alcohol Cell apoptosis
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