蔷薇红景天低聚原花青素对动脉粥样硬化大鼠肝脏的保护作用
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摘要
目的:研究蔷薇红景天低聚原花青素(oligomeric procyanidins from Rhodiola rosea L.,OPCRR)对动脉粥样硬化(atherosclerosis,AS)大鼠肝脏的保护作用。方法:采用VD3结合高脂乳剂灌胃的方法建立大鼠AS模型。随机分为阴性对照组,模型对照组,OPCRR 60、120、240 mg/kg m_b剂量组和姜黄素(50 mg/kg m_b)对照组。连续灌胃8周后,通过分析各组大鼠肝脏的组织形态、脂质、氧化应激和炎症细胞因子等指标水平的变化,研究OPCRR对大鼠AS的干预效果。结果:与模型对照组相比,OPCRR可以显著降低大鼠血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(lowdensitylipoproteincholesterol,LDL-c)水平(P<0.05),显著提高高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-c)水平(P<0.05),并显著降低大鼠AS指数(P<0.05);OPCRR可显著减少肝脏中的炎性灶和细胞变性,减轻肝细胞的受损程度;肝组织TC、TG、LDL-c和极低密度脂蛋白胆固醇(very low density lipoprotein cholesterol,VLDL-c)水平显著下降(P<0.05),HDL-c水平显著升高(P<0.05);肝脏中丙二醛的含量显著减少,超氧化物歧化酶和谷胱甘肽过氧化酶的活力显著提高(P<0.05);同时肝脏中的白细胞介素(interleukin,IL)-1β、IL-6、IL-10、肿瘤坏死因子-α、单核细胞趋化蛋白-1和细胞间黏附因子-1水平显著下降(P<0.05)。结论:OPCRR可以通过改善肝脏中脂质代谢、氧化应激和炎症反应而起到对AS大鼠肝脏的保护作用,且整体效果优于姜黄素。
Objective: To study the hepatoprotective effect and underlying mechanism of oligomeric procyanidins from Rhodiola rosea L.(OPCRR) in rats with atherosclerosis(AS). Methods: A rat model of AS was established by orally administering vitamin D3 and a high-fat emulsion simultaneously. The animals were divided into negative control, AS model, positive control(curcumin at 50 mg/kg m_b), and low-, medium-and high-dose OPCRR(60, 120 and 240 mg/kg m_b) groups. After administration for 8 consecutive weeks, we determined the changes in liver histology, lipids, oxidative stress and inflammatory cytokines in order to evaluate the effectiveness of OPCRR in alleviating AS. Results: Compared with the AS model group, OPCRR significantly reduced the serum levels of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-c), and significantly increased serum high density lipoprotein cholesterol(HDL-c) level(P < 0.05). Meanwhile, OPCRR significantly reduced AS index, and it improved the morphology of liver cells, protected the structure of hepatic lobules, significantly reduced the num_ber of inflammatory foci and cell degeneration in the liver, and attenuated liver cell damage. Hepatic TC, TG, LDL-c and very low density lipoprotein cholesterol levels dropped significantly, and HDL-c significantly increased in the OPCRR-treated rats compared with the model control group(P < 0.05); malondialdehyde level in the liver significantly reduced, and the activities of superoxide dismutase and glutathione peroxidase increased significantly(P < 0.05). At the same time, the levels of hepatic inflammatory cytokines(interleukin(IL)-1b, IL-6, IL-10, tumor necrosis factor-α, monocyte chemoattractant protein-1 and intercellular cell adhesion molecule-1) significantly decreased(P < 0.05). Conclusion: OPCRR can protect the liver of AS rats by regulating lipid metabolism, oxidative stress and inflammation in the liver, and its effect is better than that of curcumin.
Objective: To study the hepatoprotective effect and underlying mechanism of oligomeric procyanidins from Rhodiola rosea L.(OPCRR) in rats with atherosclerosis(AS). Methods: A rat model of AS was established by orally administering vitamin D3 and a high-fat emulsion simultaneously. The animals were divided into negative control, AS model, positive control(curcumin at 50 mg/kg m_b), and low-, medium-and high-dose OPCRR(60, 120 and 240 mg/kg m_b) groups. After administration for 8 consecutive weeks, we determined the changes in liver histology, lipids, oxidative stress and inflammatory cytokines in order to evaluate the effectiveness of OPCRR in alleviating AS. Results: Compared with the AS model group, OPCRR significantly reduced the serum levels of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-c), and significantly increased serum high density lipoprotein cholesterol(HDL-c) level(P < 0.05). Meanwhile, OPCRR significantly reduced AS index, and it improved the morphology of liver cells, protected the structure of hepatic lobules, significantly reduced the num_ber of inflammatory foci and cell degeneration in the liver, and attenuated liver cell damage. Hepatic TC, TG, LDL-c and very low density lipoprotein cholesterol levels dropped significantly, and HDL-c significantly increased in the OPCRR-treated rats compared with the model control group(P < 0.05); malondialdehyde level in the liver significantly reduced, and the activities of superoxide dismutase and glutathione peroxidase increased significantly(P < 0.05). At the same time, the levels of hepatic inflammatory cytokines(interleukin(IL)-1b, IL-6, IL-10, tumor necrosis factor-α, monocyte chemoattractant protein-1 and intercellular cell adhesion molecule-1) significantly decreased(P < 0.05). Conclusion: OPCRR can protect the liver of AS rats by regulating lipid metabolism, oxidative stress and inflammation in the liver, and its effect is better than that of curcumin.
引文
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[9]魏国华,刘兰,蔡晓波,等.高脂饮食所致动脉粥样硬化家兔肝组织学损伤评估[J].中国动脉硬化杂志,2008,16(5):373-375.
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[14]马蕾.蔷薇红景天原花青素对衰老的营养干预及其作用机制研究[D].保定:河北农业大学,2014:1-13.
[15]王琛,孟哲,马艳秋,等.姜黄素对血管紧张素Ⅱ诱导血管平滑肌细胞增殖及氧化应激的影响[J].西安交通大学学报(医学版),2016,37(3):441-446.DOI:10.7652/jdyxb201603029.
[16]赵文.一种蔷薇红景天原花青素的制备方法:CN2011100915740[P].2013-08-14[2017-06-30].
[17]赵娟,李相军,孙波,等.维生素D3联合高脂饲料建立大鼠动脉粥样硬化模型[J].实用医学杂志,2009,25(21):3569-3571.
[18]吴开云,高摄渊,袁融,等.维生素D诱发大鼠动脉粥样硬化的实验研究[J].解剖学报,1996(2):133-135.DOI:10.16098/j.issn.0529-1356.1996.02.006.
[19]王伟,杨滨,王岚,等.丹参山楂药对大鼠动脉粥样硬化的影响[J].中国中药杂志,2011,36(6):784-789.
[20]YANG P Y,RUI Y C,LI K,et al.Expression of intercellular adhesion molecule-1 in U937 foam cells and inhibitory effect of imperatorin[J].Acta Pharmacologica Sinica,2002,23(4):327-330.
[21]TABAS I,WILLIAMS K J,BORéN J.Subendothelial lipoprotein retention as the initiating process in atherosclerosis update and therapeutic implications[J].Circulation,2007,116(16):1832-1844.
[22]唐妮,高静,吴晨曦,等.参芪鲫鱼药膳汤对大鼠早期动脉粥样硬化血脂及肝脏的影响[J].中国疗养医学,2015,24(11):1134-1138.DOI:10.13517/j.cnki.ccm.2015.11.006.
[23]姜岩,刘丹.原花青素预防大鼠冠状动脉粥样硬化研究[J].中国医学工程,2011(4):104;106.
[24]ZHANG Kexia,ZHANG Yuanyuan,ZHANG Meiyu,et al.Effects of phospholipid complexes of total flavonoids from persimmon(Diospyros kaki L.)leaves on experimental atherosclerosis rats[J].Journal of Ethnopharmacology,2016,191:245-253.DOI:10.1016/j.jep.2016.06.043
[25]李向阳,龚其海,吴芹,等.金钗石斛多糖对大鼠高脂血症和肝脏脂肪变性的影响[J].中国药学杂志,2010,45(15):1142-1144.
[26]李国娟,陈宏,董艳华,等.利拉鲁肽对促动脉粥样硬化饮食喂养大鼠大动脉的保护作用及对肝脏PGC-1α表达的影响[J].华中科技大学学报(医学版),2014,43(6):653-657.DOI:10.3870/j.issn.1672-0741.2014.06.009.
[27]盛冲霄,黎红华,崔敏,等.糖尿病与氧化应激在颈动脉粥样硬化大鼠内皮功能障碍中的作用研究[J].中国全科医学,2016,19(9):1015-1020.DOI:10.3969/j.issn.1007-9572.2016.09.006.
[28]MONTERO-VEGA M T.The inflammatory process underlying atherosclerosis[J].Critical Reviews in Immunology,2012,32(5):373-462.DOI:10.1615/CritRevImmunol.v32.i5.10.
[29]WEBER C,NOELS H.Atherosclerosis:current pathogenesis and therapeutic options[J].Nature Medicine,2011,17(11):1410-1422.DOI:10.1038/nm.2538.
[30]GU L,OKADA Y,CLINTON S K,et al.Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice[J].Molecular Cell,1998,2(2):275-281.DOI:10.1016/S1097-2765(00)80139-2.
[31]何忠梅,李成恩,段翠翠,等.短梗五加果多酚预防大鼠动脉粥样硬化作用研究[J].食品科学,2018,39(1):200-206.DOI:10.7506/spkx1002-6630-201801030.
[2]PANG J J,XU Q H,XU X B,et al.Hexarelin suppresses high lipid diet and vitamin D3-induced atherosclerosis in the rat[J].Peptides,2010,31(4):630-638.DOI:10.1016/j.peptides.2009.11.007.
[3]LIU Yueli,WANG Liqun,WU Haitao,et al.Comparison of antiatherosclerotic effects of two different extracts from leaves of Mallotus furetianus[J].Asian Pacific Journal of Tropical Medicine,2011,4(11):878-882.DOI:10.1016/S1995-7645(11)60212-5.
[4]DIAO S L,SUN J W,MA B X,et al.Influence of crocetin on highcholesterol diet induced atherosclerosis in rats via anti-oxidant activity together with inhibition of inflammatory response and p38 MAPKsignaling pathway[J].Saudi Journal of Biological Sciences,2016,25(3):493-499.DOI:10.1016/j.sjbs.2016.11.005.
[5]张玥,朱晓冉,蔡玥,等.灯盏花素对动脉粥样硬化大鼠氧化应激和炎症反应的影响[J].贵州医科大学学报,2017,42(1):71-75.DOI:10.19367/j.cnki.1000-2707.2017.01.016.
[6]魏刚.脂血清胶囊对高脂血症豚鼠的血脂调节及肝脏保护作用研究[D].石家庄:河北医科大学,2015:1-13.
[7]周晓欢,杨玉春,张源明,等.高血压及高脂血症与颈动脉粥样硬化的相关性分析[J].西部医学,2014,26(12):1645-1647.
[8]周筱琼,于小妹,叶雄伟,等.高脂血症患者血浆致动脉粥样硬化指数与血栓形成危险因子的相关性[J].中国动脉硬化杂志,2010,18(10):799-802.
[9]魏国华,刘兰,蔡晓波,等.高脂饮食所致动脉粥样硬化家兔肝组织学损伤评估[J].中国动脉硬化杂志,2008,16(5):373-375.
[10]CROCE K,LIBBY P.Intertwining of thrombosis and inflammation in atherosclerosis[J].Current Opinion in Hematology,2007,14(1):55-61.
[11]HORT M A,STRALIOTTO M R,DUZ M S,et al.Cardioprotective effects of a proanthocyanidin-rich fraction from Croton celtidifolius Baill:focus on atherosclerosis[J].Food and Chemical Toxicology,2012,50(10):3769-3775.DOI:10.1016/j.fct.2012.07.050.
[12]MOHANA T,NAVIN A V,JAMUNA S,et al.Inhibition of differentiation of monocyte to macrophages in atherosclerosis by oligomeric proanthocyanidins:in-vivo and in-vitro study[J].Food and Chemical Toxicology,2015,82:96-105.DOI:10.1016/j.fct.2015.04.028.
[13]孟玉彩.蔷薇红景天中原花青素提取、精制及稳定性研究[D].保定:河北农业大学,2009:1-10.
[14]马蕾.蔷薇红景天原花青素对衰老的营养干预及其作用机制研究[D].保定:河北农业大学,2014:1-13.
[15]王琛,孟哲,马艳秋,等.姜黄素对血管紧张素Ⅱ诱导血管平滑肌细胞增殖及氧化应激的影响[J].西安交通大学学报(医学版),2016,37(3):441-446.DOI:10.7652/jdyxb201603029.
[16]赵文.一种蔷薇红景天原花青素的制备方法:CN2011100915740[P].2013-08-14[2017-06-30].
[17]赵娟,李相军,孙波,等.维生素D3联合高脂饲料建立大鼠动脉粥样硬化模型[J].实用医学杂志,2009,25(21):3569-3571.
[18]吴开云,高摄渊,袁融,等.维生素D诱发大鼠动脉粥样硬化的实验研究[J].解剖学报,1996(2):133-135.DOI:10.16098/j.issn.0529-1356.1996.02.006.
[19]王伟,杨滨,王岚,等.丹参山楂药对大鼠动脉粥样硬化的影响[J].中国中药杂志,2011,36(6):784-789.
[20]YANG P Y,RUI Y C,LI K,et al.Expression of intercellular adhesion molecule-1 in U937 foam cells and inhibitory effect of imperatorin[J].Acta Pharmacologica Sinica,2002,23(4):327-330.
[21]TABAS I,WILLIAMS K J,BORéN J.Subendothelial lipoprotein retention as the initiating process in atherosclerosis update and therapeutic implications[J].Circulation,2007,116(16):1832-1844.
[22]唐妮,高静,吴晨曦,等.参芪鲫鱼药膳汤对大鼠早期动脉粥样硬化血脂及肝脏的影响[J].中国疗养医学,2015,24(11):1134-1138.DOI:10.13517/j.cnki.ccm.2015.11.006.
[23]姜岩,刘丹.原花青素预防大鼠冠状动脉粥样硬化研究[J].中国医学工程,2011(4):104;106.
[24]ZHANG Kexia,ZHANG Yuanyuan,ZHANG Meiyu,et al.Effects of phospholipid complexes of total flavonoids from persimmon(Diospyros kaki L.)leaves on experimental atherosclerosis rats[J].Journal of Ethnopharmacology,2016,191:245-253.DOI:10.1016/j.jep.2016.06.043
[25]李向阳,龚其海,吴芹,等.金钗石斛多糖对大鼠高脂血症和肝脏脂肪变性的影响[J].中国药学杂志,2010,45(15):1142-1144.
[26]李国娟,陈宏,董艳华,等.利拉鲁肽对促动脉粥样硬化饮食喂养大鼠大动脉的保护作用及对肝脏PGC-1α表达的影响[J].华中科技大学学报(医学版),2014,43(6):653-657.DOI:10.3870/j.issn.1672-0741.2014.06.009.
[27]盛冲霄,黎红华,崔敏,等.糖尿病与氧化应激在颈动脉粥样硬化大鼠内皮功能障碍中的作用研究[J].中国全科医学,2016,19(9):1015-1020.DOI:10.3969/j.issn.1007-9572.2016.09.006.
[28]MONTERO-VEGA M T.The inflammatory process underlying atherosclerosis[J].Critical Reviews in Immunology,2012,32(5):373-462.DOI:10.1615/CritRevImmunol.v32.i5.10.
[29]WEBER C,NOELS H.Atherosclerosis:current pathogenesis and therapeutic options[J].Nature Medicine,2011,17(11):1410-1422.DOI:10.1038/nm.2538.
[30]GU L,OKADA Y,CLINTON S K,et al.Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice[J].Molecular Cell,1998,2(2):275-281.DOI:10.1016/S1097-2765(00)80139-2.
[31]何忠梅,李成恩,段翠翠,等.短梗五加果多酚预防大鼠动脉粥样硬化作用研究[J].食品科学,2018,39(1):200-206.DOI:10.7506/spkx1002-6630-201801030.