0.05）。 結(jié)論: 梔子可通過上調(diào)腎臟外排轉(zhuǎn)運體Mrp2的蛋白表達，增加膽酸鹽自尿液的排泄而發(fā)揮利膽作用，這可能是梔子“引濕熱自小便而出”而發(fā)揮利膽功效的相關(guān)中醫(yī)理論的分子機制。;Objectives Gardenia Jasminoides (Zhizi in Chinese), belonging to Rubiaceae family, has been traditionally used to treat cholestasis and jaundice for centuries in Asia. In the theory of traditional Chinese medicines, Zhizi could dispel dampness and heat via the urine to execute its choleretic effects. However, the potential molecular mechanism is still poorly clarified. Here, we investigated the effect of different dose of Zhizi aqueous extracts powder on urinary excretion of bile acids (BAs), and explored the potential mechanism via renal BAs efflux transporters Mrp2 and Mrp4 in normal rats. Methods Male Wistar rats were orally administrated with 0.3 or 0.9 g/kg/d dose of Zhizi aqueous extract powder for 2 weeks, then body weight, serum aminotransferase, total BAs concentrations in liver, bile, serum, kidney, and urine, 1 h bile flow, 12-h urinary volume, biliary, and urinary excretion amount of total BAs as well as protein expression of major renal BAs efflux transporter Mrp2 and Mrp4, were all evaluated. Results Zhizi especially the high dose of Zhizi aqueous extract powder reduced hepatic total BAs concentration. Additionally, bile flow and biliary excretion had no significant difference, but the remarkable increased urinary excretion of BAs and 2 ? 3 folds up-regulated renal Mrp2 expression were observed after administrated with Zhizi as compared with the control group. Conclusion The findings indicated that Zhizi reduced hepatic total BAs level by increasing urinary excretion rather than the biliary excretion of BAs, which in turn ascribed to elevated protein expression of Mrp2 at apical membrane of renal tubular epithelial cells."/>

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Archive > Volume 10 Issue 4 > 2018,10(4):431-436. DOI:10.1016/j.chmed.2018.08.008 Prev Next

梔子上調(diào)腎臟Mrp2增加膽酸鹽自尿液外排而發(fā)揮利膽功效的機制探究

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Potential mechanism of cholagogic effect of Gardenia jasminoides Zhizi: Reduction of hepatic bile acids level by increasing urinary excretion via up-regulating renal Mrp2 in normal rats

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    摘要:
    目的：梔子是治療膽汁淤積和黃疸的常用中藥，中醫(yī)理論認為梔子可“引濕熱自小便而出”從而發(fā)揮其退黃利膽的功效，然而有關(guān)梔子利膽的分子機制目前尚未闡明。因此，實驗以正常大鼠為研究對象，通過考察不同劑量梔子水提物對膽酸鹽隨尿液排泄量的影響以及對腎臟介導(dǎo)膽酸鹽自尿液外排的主要轉(zhuǎn)運體Mrp2和Mrp4蛋白表達量的影響，探究的梔子利膽的分子機制。 方法：雄性Wistar大鼠隨機分為對照組，等效劑量組和高劑量組3組（n=6），各組大鼠分別灌胃給予純化水、0.3 g/kg/d和0.9 g/kg/d梔子水提物干燥粉末的水溶液，每天2次，連續(xù)灌胃2周。于干預(yù)結(jié)束時禁食12 h，麻醉后，收集大鼠血清、1 h膽汁和12 h尿液樣本，以及肝臟和腎臟組織樣本，測定血清轉(zhuǎn)氨酶以及各樣本中總膽酸鹽的水平，并采用Western Blotting法測定大鼠腎臟中Mrp2和Mrp4的蛋白表達量。 結(jié)果：與對照組相比，梔子水提物尤其是高劑量組可明顯降低肝臟中膽酸鹽的濃度（P<0.05），顯著增加膽酸鹽自尿液的排泄總量（P<0.05）并上調(diào)腎臟Mrp2的蛋白表達量（P<0.05），但其對膽汁流速、膽酸鹽自膽汁排泄量及腎臟Mrp4蛋白表達量無顯著影響（P>0.05）。 結(jié)論: 梔子可通過上調(diào)腎臟外排轉(zhuǎn)運體Mrp2的蛋白表達，增加膽酸鹽自尿液的排泄而發(fā)揮利膽作用，這可能是梔子“引濕熱自小便而出”而發(fā)揮利膽功效的相關(guān)中醫(yī)理論的分子機制。

    Abstract:
    Objectives Gardenia Jasminoides (Zhizi in Chinese), belonging to Rubiaceae family, has been traditionally used to treat cholestasis and jaundice for centuries in Asia. In the theory of traditional Chinese medicines, Zhizi could dispel dampness and heat via the urine to execute its choleretic effects. However, the potential molecular mechanism is still poorly clarified. Here, we investigated the effect of different dose of Zhizi aqueous extracts powder on urinary excretion of bile acids (BAs), and explored the potential mechanism via renal BAs efflux transporters Mrp2 and Mrp4 in normal rats. Methods Male Wistar rats were orally administrated with 0.3 or 0.9 g/kg/d dose of Zhizi aqueous extract powder for 2 weeks, then body weight, serum aminotransferase, total BAs concentrations in liver, bile, serum, kidney, and urine, 1 h bile flow, 12-h urinary volume, biliary, and urinary excretion amount of total BAs as well as protein expression of major renal BAs efflux transporter Mrp2 and Mrp4, were all evaluated. Results Zhizi especially the high dose of Zhizi aqueous extract powder reduced hepatic total BAs concentration. Additionally, bile flow and biliary excretion had no significant difference, but the remarkable increased urinary excretion of BAs and 2 ? 3 folds up-regulated renal Mrp2 expression were observed after administrated with Zhizi as compared with the control group. Conclusion The findings indicated that Zhizi reduced hepatic total BAs level by increasing urinary excretion rather than the biliary excretion of BAs, which in turn ascribed to elevated protein expression of Mrp2 at apical membrane of renal tubular epithelial cells.

    關(guān)鍵詞:
    梔子，利膽功效，膽酸鹽，尿液排泄，Mrp2

    Keywords:


    Project Supported:
    Prof. Xinan Wu’s and Dr. Yuhui Wei’s the National Natural Science Foundation of China (Number: 81373494 and 81373927)

    Clc Number:

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