利福平诱导小鼠脂肪肝实验模型的研究
发布时间：2018-08-19 10:31
【摘要】：目的观察利福平(RIF)引起的小鼠肝脏脂肪变及其动态演变过程,为进一步探讨药物性脂肪肝的机制奠定基础。方法将42只成年健康雄性ICR小鼠随机分为7组(对照组,RIF 8 h、24 h、3 d、1周、2周、4周组),经灌胃给予RIF处理(200 mg/kg),末次给药后禁食6 h处死小鼠,采集血液及肝脏组织。计算肝脏系数;检测血清丙氨酸氨基转移酶(ALT)活性;HE染色观察肝脏组织病理学改变;检测血清中三酰甘油(TG)、胆固醇酯(TCH)、高密度脂蛋白(HDL)、极低密度脂蛋白(VLDL)水平;检测肝脏组织中TG水平;油红O染色检测肝脏组织脂质沉积。结果与对照组比较,RIF处理组小鼠肝脏重量、系数均从24 h开始逐渐升高,4周时达到高峰;与对照组比较,24 h、3 d、1周、2周组ALT水平逐渐升高,4周组ALT水平显著升高。HE染色显示8、24h组肝脏组织无明显变化,3 d组可见小的空泡,而从1周开始出现显著增多的大的圆形空泡。8、24 h组血清中TG和VLDL水平较对照组轻度升高,3 d时升高最明显,而1、2、4周组中呈下降趋势,且显著低于对照组。RIF处理各组血清TCH、HDL水平均较对照组降低。肝脏组织TG含量从8 h开始明显升高,1周时达峰值,之后2、4周组呈下降趋势但仍显著高于对照组。油红O染色结果显示,8、24 h组肝脏组织中可见少量脂质沉积,从3 d组开始出现显著增多的大圆形脂滴。结论 RIF能引起小鼠肝脏组织中脂质沉积,且呈明显的时间效应关系。
[Abstract]:Objective to observe the steatosis and dynamic evolution of livers induced by rifampicin (RIF) in mice, and to lay a foundation for further study on the mechanism of drug induced fatty liver. Methods 42 healthy adult male ICR mice were randomly divided into 7 groups (control group: control group, 8 h, 24 h, 3 d, 1 week, 2 weeks and 4 weeks). The mice were treated with RIF (200 mg/kg), and the mice were sacrificed at 6 h after the last administration. Blood and liver tissues were collected. Liver coefficient was calculated, serum alanine aminotransferase (ALT) activity was detected by HE staining, liver histopathology was observed, serum triacylglycerol (TG), cholesterol ester (TCH), high density lipoprotein (HDL), very low density lipoprotein (VLDL) was detected. TG level in liver tissue and lipid deposition in liver tissue were detected by oil red O staining. Results compared with the control group, the liver weight of RIF treated mice increased gradually from 24 h to reach the peak at 4 weeks. Compared with the control group, the level of ALT increased gradually in the group of 24 h and 3 d and 2 weeks. The level of ALT in the group of 4 weeks was significantly increased. The HE staining showed that there was no obvious change in liver tissue in the group of 824 h after 3 days. Small vacuoles were found in the group 3 days after treatment. However, the serum TG and VLDL levels in the 24 h group with large circular vacuoles increased significantly from week 1 to week 1, which were significantly higher than those in the control group at 3 d after slight increase, but decreased in the 4 week group. Compared with the control group, the serum TCHF HDL level in RIF group was significantly lower than that in the control group. The content of TG in liver tissue increased significantly from 8 hours to the peak at 1 week, then decreased in the group of 2 ~ 4 weeks, but still significantly higher than that in the control group. The results of oil red O staining showed that a small amount of lipid deposition was observed in the liver tissues of the rats in the 824 h group, and a significant increase of large circular lipid droplets began to appear in the 3 d group. Conclusion RIF can induce lipid deposition in the liver tissue of mice, and has a time-dependent relationship.
【作者单位】： 安徽医科大学第一附属医院消化内科安徽省消化系统疾病重点实验室;安徽医科大学卫生毒理学系;
【基金】：国家自然科学基金(编号:81001480) 2013年高等学校博士学科点专项(编号:20133420110005) 安徽省自然科学基金(编号:1308085MH120) 安徽省高校省级自然科学研究重点项目(编号:KJ2011A159) 安徽省高等学校省级优秀青年人才基金项目(编号:2011SQRL058ZD)
【分类号】：R965;R-332
[Abstract]:Objective to observe the steatosis and dynamic evolution of livers induced by rifampicin (RIF) in mice, and to lay a foundation for further study on the mechanism of drug induced fatty liver. Methods 42 healthy adult male ICR mice were randomly divided into 7 groups (control group: control group, 8 h, 24 h, 3 d, 1 week, 2 weeks and 4 weeks). The mice were treated with RIF (200 mg/kg), and the mice were sacrificed at 6 h after the last administration. Blood and liver tissues were collected. Liver coefficient was calculated, serum alanine aminotransferase (ALT) activity was detected by HE staining, liver histopathology was observed, serum triacylglycerol (TG), cholesterol ester (TCH), high density lipoprotein (HDL), very low density lipoprotein (VLDL) was detected. TG level in liver tissue and lipid deposition in liver tissue were detected by oil red O staining. Results compared with the control group, the liver weight of RIF treated mice increased gradually from 24 h to reach the peak at 4 weeks. Compared with the control group, the level of ALT increased gradually in the group of 24 h and 3 d and 2 weeks. The level of ALT in the group of 4 weeks was significantly increased. The HE staining showed that there was no obvious change in liver tissue in the group of 824 h after 3 days. Small vacuoles were found in the group 3 days after treatment. However, the serum TG and VLDL levels in the 24 h group with large circular vacuoles increased significantly from week 1 to week 1, which were significantly higher than those in the control group at 3 d after slight increase, but decreased in the 4 week group. Compared with the control group, the serum TCHF HDL level in RIF group was significantly lower than that in the control group. The content of TG in liver tissue increased significantly from 8 hours to the peak at 1 week, then decreased in the group of 2 ~ 4 weeks, but still significantly higher than that in the control group. The results of oil red O staining showed that a small amount of lipid deposition was observed in the liver tissues of the rats in the 824 h group, and a significant increase of large circular lipid droplets began to appear in the 3 d group. Conclusion RIF can induce lipid deposition in the liver tissue of mice, and has a time-dependent relationship.
【作者单位】： 安徽医科大学第一附属医院消化内科安徽省消化系统疾病重点实验室;安徽医科大学卫生毒理学系;
【基金】：国家自然科学基金(编号:81001480) 2013年高等学校博士学科点专项(编号:20133420110005) 安徽省自然科学基金(编号:1308085MH120) 安徽省高校省级自然科学研究重点项目(编号:KJ2011A159) 安徽省高等学校省级优秀青年人才基金项目(编号:2011SQRL058ZD)
【分类号】：R965;R-332
【参考文献】
相关期刊论文 前3条
1 曹云海;陈熙;张程;石嫦娥;徐德祥;许建明;;利福平对小鼠肝细胞胆汁酸转运体Bsep和Mrp2表达与定位的影响[J];中国药理学通报;2010年12期
2 徐娟;陈熙;张程;段自v，
本文编号：2191400
本文链接：https://www.wllwen.com/yixuelunwen/yiyaoxuelunwen/2191400.html
最近更新
教材专著
