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银杏内酯B抑制非酒精性脂肪性肝病大鼠肝脏极低密度脂蛋白输出 被引量:5

Ginkgolide B inhibits very-low-density lipoprotein output in liver of rats with non-alcoholic fatty liver disease
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摘要 目的:探讨银杏内酯B对高脂高糖饮食诱导的非酒精性脂肪性肝病大鼠肝脏极低密度脂蛋白(VLDL)输出的影响。方法:72只SD大鼠适应性喂养10 d后按照随机数字表法分为正常对照(CON)组、模型(MOD)组、阳性药物辛伐他汀(SIM)组及银杏内酯B低、中和高剂量治疗组,每组12只。除对照组外,大鼠采用高脂高糖饮食喂养12周后,每组随机选取2只检测造模是否成功。造模成功后给予治疗,其中CON组和MOD组大鼠给予1 mL·kg^(−1)·d^(−1)生理盐水灌胃治疗,SIM组大鼠给予2 mg·kg^(−1)·d^(−1) SIM治疗,银杏内酯B低、中和高剂量治疗组大鼠分别给予0.5、1.0和2.0 mg·kg^(−1)·d^(−1)银杏内酯B治疗,治疗4周后,收集大鼠血液检测肝功能和血脂(VLDL和LDL)水平,收集肝脏检测肝脏组织病理学、肝脂(VLDL和LDL)水平,同时采用免疫荧光和Western blot检测肝脏组织中VLDL合成关键蛋白微粒体甘油三酯转运蛋白(MTP)和载脂蛋白B-100(ApoB-100)的表达。结果:与CON组相比,MOD组血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、VLDL和LDL及肝脏中VLDL和LDL均显著升高(P<0.05);与MOD组相比,SIM组和银杏内酯B各治疗组上述指标均显著降低(P<0.05)。肝脏病理学显示,正常组细胞排列整齐,细胞大小均一,细胞核基本都分布于细胞中央;而MOD组则弥漫有大量脂肪空泡,细胞核受到挤压紧贴于细胞膜分布;各治疗组相较于MOD组细胞形态明显好转。与CON组相比,MOD组肝脏内MTP和ApoB-100表达均显著升高(P<0.05),而SIM和银杏内酯B均可显著降低二者表达(P<0.05)。结论:银杏内酯B可通过调控MTP和ApoB-100表达降低非酒精性脂肪性肝病大鼠肝脏VLDL的输出,进而保护肝脏。 AIM:To study the effect of ginkgolide B on the output of very low-density lipoprotein(VLDL)in rats with non-alcoholic fatty liver disease induced by a high-fat and high-sugar diet.METHODS:After 10 d of adaptive feeding,72 SD rats were randomly divided into normal control(CON)group,model(MOD)group,positive drug simvastatin(SIM)group,and low-,medium-and high-dose ginkgolide B treatment(GB-L,GB-M and GB-H)groups via random number table method(n=10).After all rats except control rats were received a high-fat and high-sugar diet for 12 weeks,2 animals were randomly selected to test whether the modeling was successful built or not from each group.The rats in CON group and MOD group were treated with 1 mL·kg^(−1)·d^(−1) saline,the rats in SIM group were treated with 2 mg·kg^(−1)·d^(−1) simvastatin,and the rats in the 3 doses of ginkgolide B groups were treated with ginkgolide B at 0.5,1.0 and 2.0 mg·kg^(−1)·d^(−1),respectively.After 4 weeks,the blood was collected for liver function and lipid(VLDL and LDL)determination,and the liver was collected for liver histopathological observation,hepatic lipid(VLDL and LDL)testing and detection of microsomal triglyceride transfer protein(MTP)and apolipoprotein B-100(ApoB-100)protein expression by immunofluorescence and Western blot.RESULTS:Compared with CON group,alanine aminotransferase(ALT),aspartate aminotransferase(AST),VLDL and LDL in serum,VLDL and LDL in liver tissues were significantly increased in MOD group(P<0.05).Compared with MOD group,the above indicators were significantly reduced in SIM group and 3 ginkgolide B groups(P<0.05).The liver histopathological observation showed that the cells in CON group were neatly arranged,uniform in size,and the nuclei were basically distributed in the center of the cells.The slices in MOD group were filled with a large number of fat vacuoles,and the nuclei were squeezed and distributed close to the cell membrane.The cell morphological changes in each treatment group were significantly better than those in MOD group.
作者 武俊紫 赵茜 罗德霞 范晓明 马琼 石安华 WU Jun-zi;ZHAO Xi;LUO De-xia;FAN Xiao-ming;Ma Qiong;SHI An-hua(School of Basic Medicine,Yunnan University of Chinese Medicine,Kunming 650504,China;Laboratory of Microcosmic Syndrome Differentiation,Education Department of Yunnan,Kunming 650500,China;Guangxi Key Laboratory of Sys-tematic Medicine,Guilin Medical College,Guilin 541100,China)
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2021年第2期300-305,共6页 Chinese Journal of Pathophysiology
基金 国家自然科学基金项目(No.81760818) 云南省科学技术厅-中医联合专项面上项目[No.2019FF002(-041),No.2019FF02(-055)]。
关键词 银杏内酯B 非酒精性脂肪性肝病 极低密度脂蛋白 载脂蛋白B-100 微粒体甘油三酯转运蛋白 Ginkgolide B Non-alcoholic fatty liver disease Very low density lipoprotein Apolipoprotein B-100 Microsomal triglyceride transper protein
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