罗格列酮对小鼠高胆固醇血症的治疗作用、肝脏胆汁酸代谢影响及其机制探讨

发布时间：2018-03-11 18:25

本文选题：罗格列酮　切入点：高胆固醇血症　出处：《山东医药》2017年31期 　论文类型：期刊论文

【摘要】：目的观察罗格列酮对小鼠高胆固醇血症的治疗作用、肝脏胆汁酸代谢影响,并探讨其可能机制。方法36只小鼠随机分为3组各12只,干预组和模型组均制备高胆固醇血症模型,并分别灌胃罗格列酮羧甲基纤维素钠混悬液、空白羧甲基纤维素钠溶液,持续给予高脂饲料;正常组每日灌胃等体积羧甲基纤维素钠溶液,始终给予普通饲料。观察各组组织病理学及血生化指标[血糖、血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)]变化。液质联用仪分析肝脏组织中胆汁酸丰度。另检测肝脏或肠组织中Cyp7a1、Cyp8b1、FXR、SHP、Lrh1、Hnf4α、Fgf15、Fgfr4、JNK1/2、ERK1/2基因。结果模型组肝细胞中充斥大量脂肪泡,干预组细胞内脂肪泡接近正常组。与模型组比较,干预组TC、LDL、血糖水平降低,ALT水平升高,P均0.05。模型组TCA显著下降,但干预组没有能逆转其下降的趋势;模型组DCA无太大变化,但干预组DCA急剧上升,远远超过对照组。与模型组比较,干预组JNK1、Erk2、Cyp7a1、FXR表达升高,SHP表达降低,P均0.05。结论罗格列酮对小鼠高胆固醇血症有治疗作用,且影响肝脏胆汁代谢,其机制可能为调控胆汁酸代谢通路基因表达,影响胆汁酸组的整体轮廓特征。
[Abstract]:Objective to observe the therapeutic effect of rosiglitazone on hypercholesterolemia in mice and the effect of hepatic bile acid metabolism and to explore its possible mechanism. Methods 36 mice were randomly divided into 3 groups (12 mice each), and hypercholesterolemia models were established in both the intervention group and the model group. Rosiglitazone sodium carboxymethyl cellulose suspension and blank sodium carboxymethyl cellulose solution were given continuously with high fat diet. The normal group was given sodium carboxymethyl cellulose solution of the same volume daily. Observe histopathology and blood biochemical indexes [blood glucose, blood glucose]. Serum total cholesterol, low density lipoprotein cholesterol (LDL-Cn), alanine aminotransferase (alt), glutamic oxalacetic transaminase (AST)]. The bile acid abundance in liver tissue was analyzed by liquid / mass spectrometry. The liver tissue was also detected for Cyp7a1Cyp8b1FXRSHP1Hnf4 伪 Fgf15Fgfr4JNK1 / 2ERK1- 2 gene. Results the liver tissue of the model group was treated with Cyp7a1Cyp8b1FXRHnf4 伪 -Fgf15 Fgfr4JNK1 / 2 ERK1 / 2 gene. The cells are filled with fat bubbles, Compared with the model group, compared with the model group, the plasma glucose level decreased and alt level increased in the intervention group (P < 0.05). The TCA decreased significantly in the model group, but it did not reverse the decreasing trend in the intervention group, and the DCA in the model group did not change significantly. Compared with the model group, the expression of JNK1Erk2Cyp7a1FXR in the intervention group increased and the expression of SHP decreased by 0.05.Conclusion rosiglitazone has a therapeutic effect on hypercholesterolemia in mice and affects the bile metabolism of liver. The mechanism may be to regulate the gene expression of bile acid metabolic pathway and affect the overall profile of bile acid group.
【作者单位】：遵义医学院国家级药学实验教学示范中心药学实验室;遵义医学院基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室;遵义医学院附属医院;
【基金】：国家自然科学基金资助项目(81402985,81560673,81660685) 贵州省科技重大专项(黔科合重大专项字[2015]6010) 贵州省科学技术基金(黔科合J字[2015]2158号,黔科合JZ字[2015]2010号) 贵州省出国留学人员择优资助计划(黔人项目资助合同(2015)03号) 上海市复方中药重点实验室开放基金(14DZ2271000) 国家级/省级大学生创新创业项目(201510661002) 遵义医学院大学生创新创业项目(遵医[2015]5046) 贵州省药剂学研究生卓越人才培养计划(黔教研合ZYRC字[2014]019)
【分类号】：R965

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