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利福平誘導小鼠脂肪肝實驗模型的研究

發(fā)布時間:2018-08-19 10:31
【摘要】:目的觀察利福平(RIF)引起的小鼠肝臟脂肪變及其動態(tài)演變過程,為進一步探討藥物性脂肪肝的機制奠定基礎(chǔ)。方法將42只成年健康雄性ICR小鼠隨機分為7組(對照組,RIF 8 h、24 h、3 d、1周、2周、4周組),經(jīng)灌胃給予RIF處理(200 mg/kg),末次給藥后禁食6 h處死小鼠,采集血液及肝臟組織。計算肝臟系數(shù);檢測血清丙氨酸氨基轉(zhuǎn)移酶(ALT)活性;HE染色觀察肝臟組織病理學改變;檢測血清中三酰甘油(TG)、膽固醇酯(TCH)、高密度脂蛋白(HDL)、極低密度脂蛋白(VLDL)水平;檢測肝臟組織中TG水平;油紅O染色檢測肝臟組織脂質(zhì)沉積。結(jié)果與對照組比較,RIF處理組小鼠肝臟重量、系數(shù)均從24 h開始逐漸升高,4周時達到高峰;與對照組比較,24 h、3 d、1周、2周組ALT水平逐漸升高,4周組ALT水平顯著升高。HE染色顯示8、24h組肝臟組織無明顯變化,3 d組可見小的空泡,而從1周開始出現(xiàn)顯著增多的大的圓形空泡。8、24 h組血清中TG和VLDL水平較對照組輕度升高,3 d時升高最明顯,而1、2、4周組中呈下降趨勢,且顯著低于對照組。RIF處理各組血清TCH、HDL水平均較對照組降低。肝臟組織TG含量從8 h開始明顯升高,1周時達峰值,之后2、4周組呈下降趨勢但仍顯著高于對照組。油紅O染色結(jié)果顯示,8、24 h組肝臟組織中可見少量脂質(zhì)沉積,從3 d組開始出現(xiàn)顯著增多的大圓形脂滴。結(jié)論 RIF能引起小鼠肝臟組織中脂質(zhì)沉積,且呈明顯的時間效應關(guān)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.
【作者單位】: 安徽醫(yī)科大學第一附屬醫(yī)院消化內(nèi)科安徽省消化系統(tǒng)疾病重點實驗室;安徽醫(yī)科大學衛(wèi)生毒理學系;
【基金】:國家自然科學基金(編號:81001480) 2013年高等學校博士學科點專項(編號:20133420110005) 安徽省自然科學基金(編號:1308085MH120) 安徽省高校省級自然科學研究重點項目(編號:KJ2011A159) 安徽省高等學校省級優(yōu)秀青年人才基金項目(編號:2011SQRL058ZD)
【分類號】:R965;R-332

【參考文獻】

相關(guān)期刊論文 前3條

1 曹云海;陳熙;張程;石嫦娥;徐德祥;許建明;;利福平對小鼠肝細胞膽汁酸轉(zhuǎn)運體Bsep和Mrp2表達與定位的影響[J];中國藥理學通報;2010年12期

2 徐娟;陳熙;張程;段自v,

本文編號:2191400


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