本文關(guān)鍵詞： 辛伐他汀 調(diào)脂藥 膽汁酸類和鹽類 膽固醇　出處：《中國新藥與臨床雜志》2017年09期 　論文類型：期刊論文

【摘要】：目的研究辛伐他汀對高膽固醇血癥小鼠膽汁酸代謝通路的調(diào)控。方法 C57/BL小鼠隨機分為正常對照組、模型組和辛伐他汀(20 mg·kg~(-1)·d~(-1))組。采用高脂飲食喂養(yǎng)16周制備高膽固醇血癥模型,造模成功后給藥22周,取肝臟組織HE染色,化學(xué)法測定血清總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)、丙氨酸轉(zhuǎn)氨酶(ALT)及天冬氨酸轉(zhuǎn)氨酶(AST)水平,實時定量PCR檢測肝臟或腸組織中Cyp7a1、Cyp8b1、Fxr、Shp、Lrh1、Hnf4α、Fgf15、Fgfr4、Jnk1/2及Erk1/2的基因表達,液質(zhì)聯(lián)用技術(shù)分析肝臟中膽汁酸的含量。結(jié)果辛伐他汀顯著降低了高膽固醇血癥小鼠的TC及LDL-C水平(P0.05),改善了肝細胞內(nèi)的脂肪蓄積,但是同時引起了ALT的異常升高,出現(xiàn)了肝損傷征兆。在膽汁酸通路的基因表達水平上,辛伐他汀可顯著改善高脂飲食造成的膽汁酸通路相關(guān)基因的抑制,尤其是回調(diào)了膽汁酸合成關(guān)鍵酶Cyp7a1的基因表達(P0.05),對Fxr、Fgf15、Jnk1/2及Erk1/2等相關(guān)基因也有顯著上調(diào)作用(P0.05)。辛伐他汀對膽汁酸調(diào)控腸肝循環(huán)通路基因Fgf15等有顯著的回調(diào)作用(P0.05),但是對膽汁酸合成的關(guān)鍵酶Cyp8b1的抑制沒有回調(diào)作用。肝臟膽汁酸含量在高脂飲食壓力下顯著抑制(P0.05),辛伐他汀對部分膽汁酸的肝臟豐度抑制程度加劇(P0.01)。結(jié)論辛伐他汀對膽汁酸通路中關(guān)鍵基因有顯著的調(diào)控作用。
[Abstract]:Objective to study the regulation of simvastatin on bile acid metabolism pathway in hypercholesterolemia mice. Methods C57 / BL mice were randomly divided into normal control group. Model group and simvastatin 20 mg 路kg ~ (-1) 路d ~ (-1) group were fed with high-fat diet for 16 weeks to establish hypercholesterolemia model. The liver tissues were stained with HE and the levels of serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), alanine aminotransferase (alt) and aspartate aminotransferase (AST) were determined by chemical method. Real time quantitative PCR was used to detect the Fgfr4 偽 of Cyp7a1Cyp8b1Cyp8b1FxrHnf4 偽 and Fgf15 Fgfr4 in liver or intestine. Gene expression of Jnk1/2 and Erk1/2. Results Simvastatin significantly decreased TC and LDL-C levels in hypercholesterolemia mice and improved lipid accumulation in liver cells. At the same time, simvastatin can significantly improve the inhibition of genes associated with bile acid pathway caused by high fat diet in the level of gene expression of bile acid pathway. In particular, the gene expression of Cyp7a1, a key enzyme of bile acid synthesis, was corrected by P0.05, and Fxr-Fgf15. Jnk1/2, Erk1/2 and other related genes were also significantly up-regulated. Simvastatin had a significant callback effect on bile acid regulation of intestinal and hepatic circulation pathway gene Fgf15 (. P0.05). However, the inhibition of Cyp8b1, a key enzyme of bile acid synthesis, was not reversed. Liver bile acid content was significantly inhibited under high fat diet stress (P 0.05). The inhibition degree of simvastatin on the hepatic abundance of some bile acids was aggravated by P0.01.Conclusion Simvastatin plays a significant role in regulating the key genes in bile acid pathway.
【作者單位】： 遵義醫(yī)學(xué)院藥學(xué)院國家級藥學(xué)實驗教學(xué)示范中心藥學(xué)實驗室;上海中醫(yī)藥大學(xué)上海市復(fù)方中藥重點實驗室;遵義醫(yī)學(xué)院基礎(chǔ)藥理教育部重點實驗室暨特色民族藥教育部國際合作聯(lián)合實驗室;遵義醫(yī)學(xué)院附屬醫(yī)院藥劑科;
【基金】：國家自然科學(xué)基金(81402985,81560673,81660685) 貴州省科技重大專項(黔科合重大專項字[2015]6010) 貴州省科學(xué)技術(shù)基金(黔科合J字[2015]2158號,黔科合JZ字[2015]2010號) 貴州省出國留學(xué)人員擇優(yōu)資助計劃(黔人項目資助合同(2015)03號) 上海市復(fù)方中藥重點實驗室開放基金(14DZ2271000) 國家級/省級大學(xué)生創(chuàng)新創(chuàng)業(yè)項目(201510661002) 遵義醫(yī)學(xué)院大學(xué)生創(chuàng)新創(chuàng)業(yè)項目(遵醫(yī)[2015]5046) 貴州省藥劑學(xué)研究生卓越人才培養(yǎng)計劃(黔教研合ZYRC字[2014]019)
【分類號】：R965

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