本文關(guān)鍵詞：Triton WR-1399通過影響VLDL-C代謝通路和RCT誘導(dǎo)急性HLP小鼠模型的研究　出處：《中國藥理學(xué)通報(bào)》2017年03期 　論文類型：期刊論文

  更多相關(guān)文章： Triton WR- 高脂血癥模型 基因表達(dá) VLDL-C HMGCR LPL 非諾貝特

【摘要】：目的觀察肌肉注射化學(xué)表面活化劑Triton WR-1399誘導(dǎo)小鼠急性高脂血癥模型,考察時(shí)效和量效關(guān)系,并從基因水平探討Triton WR-1399誘發(fā)高脂血癥動(dòng)物模型的機(jī)制。方法用肌肉注射的方式分別給予小鼠0.4 g·kg~(-1),0.8 g·kg~(-1)和1.5 g·kg~(-1)的Triton WR-1399,取血時(shí)間點(diǎn)為24、32、48、56、72、80和96 h,觀察這7個(gè)時(shí)間點(diǎn)小鼠甘油三酯(TG)、膽固醇(TC)、低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)的變化;采用熒光定量PCR(RT-q PCR)法檢測脂蛋白脂肪酶(LPL),膽固醇脂酰轉(zhuǎn)移酶(LCAT),膽固醇7-羥化酶(CYP7A1),載脂蛋白AI(Apo AI),載脂蛋白(Apo B),低密度脂蛋白受體(LDLR),B類Ⅰ型清道夫受體(SRB1)和羥甲基戊二酰輔酶A還原酶(HMGCR)的脂質(zhì)代謝相關(guān)通路基因mRNA相對表達(dá)量變化�；谀Ｐ蛷�(fù)制方法考察,研究貝特類和他汀類代表藥物的調(diào)脂作用,驗(yàn)證模型的穩(wěn)定性。結(jié)果 Triton WR-1399(0.8 g·kg~(-1),1.5 g·kg~(-1))劑量組的TC、TG和LDL-C水平明顯升高,LPL、LDLR、Apo B和SRB1的基因相對表達(dá)明顯降低,HMGCR的基因相對表達(dá)明顯升高;非諾貝特對該急性模型有明顯降脂作用。結(jié)論采用肌肉注射0.8 g·kg~(-1)Triton WR-1399所誘導(dǎo)的急性高脂血癥小鼠模型穩(wěn)定,可用于調(diào)脂藥物篩選,其誘導(dǎo)模型的機(jī)制可能與抑制VLDL-C代謝通路和阻斷膽固醇逆向轉(zhuǎn)運(yùn)過程有關(guān)。基于該模型的發(fā)病機(jī)制,非諾貝特比瑞舒伐他汀表現(xiàn)出更為明顯的降脂作用。
[Abstract]:Objective To observe the acute hyperlipidemia model induced by intramuscular injection of chemical surface activator Triton WR-1399, investigate the relationship between aging and dose effect, and explore the mechanism of Triton WR-1399 induced hyperlipidemia animal model from gene level. Methods 0.4 g mice were treated with kg~ intramuscular injection mode (-1), 0.8 g - kg~ (-1) and 1.5 g kg~ (-1) Triton WR-1399, blood sampling time points of 24, 32, 48, 56, 72, 80 and 96 h, observe the 7 time points of mouse triglyceride (TG), cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) changes; fluorescent quantitative PCR (RT-q PCR) method for the detection of lipoprotein lipase (LPL), cholesterol acyl transferase (LCAT), cholesterol 7- hydroxylase (CYP7A1), apolipoprotein AI (Apo AI), apolipoprotein (Apo B), low density lipoprotein receptor (LDLR), scavenger receptor class B type 1 (SRB1) and two HMG coenzyme A reductase (HMGCR) mRNA expression of lipid metabolism related genes of mRNA pathway. Based on the model replication method, the lipid regulating effect of bets and statins was studied to verify the stability of the model. The results of Triton WR-1399 (0.8 g - kg~ (-1), 1.5 g - kg~ (-1)) dose group TC, TG and LDL-C levels were significantly increased, the relative expression of LPL, LDLR, Apo, B and SRB1 genes were significantly decreased, the relative expression of HMGCR gene significantly increased; fenofibrate has obvious lipid-lowering effect on the acute model. Conclusion the mouse model of acute hyperlipidemia induced by intramuscular injection of 0.8 g kg~ (-1) Triton WR-1399 is stable, and can be used for screening lipid lowering drugs. The mechanism of its induced model may be related to inhibiting VLDL-C metabolic pathway and blocking the reverse cholesterol transport process. Mechanism based on this model, Liberia fenofibrate rosuvastatin showed more obvious lipid-lowering effect.
【作者單位】： 廣州中醫(yī)藥大學(xué);廣東省中醫(yī)藥工程技術(shù)研究院;廣東省中醫(yī)藥研究開發(fā)重點(diǎn)實(shí)驗(yàn)室;廣州中醫(yī)藥大學(xué)第二臨床醫(yī)學(xué)院;
【基金】：廣東省科技廳資助項(xiàng)目(No 2015A040404030,2014A070705014,2013B060300034) 廣東省中醫(yī)藥管理局資助項(xiàng)目(No 20151013,20152006,20161026,20141028)
【分類號(hào)】：R589.2;R-332
【正文快照】： R972.6;R977.6HMGCR;LPL;非諾貝特高脂血癥(hyperlipidemia,HLP),即脂質(zhì)代謝紊亂引起的多種脂質(zhì)水平異常,是導(dǎo)致脂肪肝、動(dòng)脈粥樣硬化及心腦血管損害等多種疾病的重要因素[1]。因此,為篩選防治高脂血癥的藥物及其藥效評(píng)價(jià)提供有效且穩(wěn)定的動(dòng)物模型顯得尤為重要。Triton WR-139

【相似文獻(xiàn)】

相關(guān)期刊論文 前1條

1 崔旭華;王炳欣;呂娟;劉建梅;陳倩;;由常規(guī)脂質(zhì)分析資料評(píng)價(jià)血清VLDL-C和LDL-C的應(yīng)用[J];寧夏醫(yī)學(xué)雜志;1988年03期

，

本文編號(hào)：1344236