目的 研究决明子分散片对大鼠急性肝损伤的保护作用及其谱效关系。方法 将决明子分散片按高、中、低(生药量:9.26、4.63、1.54 g·kg-1)3个剂量给大鼠灌胃给药,连续给药7 d,末次给药10 h后,用四氯化碳橄榄油溶液(四氯化碳-橄榄油=1∶1,2 mL·kg-1)造模,24 h后,取出肝脏,观察外观,制作病理切片,测定血清中天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)和丙氨酸氨基转移酶(alanine aminotransferase,ALT)的含量。建立决明子分散片的HPLC指纹图谱,采用灰关联度法研究决明子分散片对大鼠急性肝损伤保护作用的谱效关系。结果 决明子分散片能明显减轻大鼠肝脏病变,并且显著降低大鼠血清AST和ALT的含量。10批决明子分散片有63个共有峰。随着给药剂量由1.54 g·kg-1增加到9.26 g·kg-1,决明子分散片各共有峰与AST的关联度逐渐增加,但与ALT的关联度先增加后降低。不同给药剂量关联度随共有峰的变化趋势基本一致,但29号峰(橙黄决明素)与AST的关联度先增加后降低,与ALT的关联度逐渐降低。高、中、低3个剂量的关联序不一致,AST的关联序分别为(前15个色谱峰):54>32>40>29>42>37>56>62>33>60(大黄酚)>24>27>52>36(大黄酸)>63(大黄素甲醚);29>32>40>54>42>37>56>62>33>60>24>52>27>36>63;29>54>32>40>42>37>56>62>33>60>24>27>52>36>63。ALT的关联序分别为(前15个色谱峰):32>42>40>37>54>56>62>29>33>60>24>52>27>36>63;29>54>32>40>42>37>56>62>33>60>24>27>52>36>63;
29>32>54>40>42>37>56>62>33>60>24>52>27>36>63。结论 决明子分散片对大鼠急性肝损伤的保护作用来自与给药剂量有关的多种活性成分之间的协同或拮抗作用。随着给药剂量的不同,发挥作用的化学成分的关联顺序并不相同,但3个剂量组发挥药效的主要成分较为一致,该成分群的存在为决明子分散片的深入研究奠定了基础。
Abstract
OBJECTIVE To investigate the protective effect and spectrum effect relationship of Cassia seed dispersible tablets on acute liver injury in rats. METHODS Cassia seed dispersive tablets were administered to rats by gavage at high, medium, and low dosages (crude drug dose: 9.26, 4.63, 1.54 g·kg-1) continuously for 7 days. Ten hours after the last administration, the animal model was made with carbon tetrachloride olive oil solution (carbon tetrachloride-olive oil, 1∶1, 2 mL·kg-1). After 24 h, the liver was taken out, the appearance was observed, pathological sections was made, and the contents of AST and ALT in serum were measured. The HPLC fingerprint of Cassia seed dispersive tablets was established, the spectrum effect relationship on the protective effect of acute liver injury in rats was investigated by gray matter association method. RESULTS Cassia seed dispersible tablets could significantly alleviate liver lesions in rats, and significantly decreased serum AST and ALT levels. The 10 batches of Cassia seed dispersible tablets had 63 common peaks. As the dosage increased from 1.54 g·kg-1 to 9.26 g·kg-1, the association degree of each consensus peak of Cassia seed dispersible tablets with AST gradually increased, but the association with ALT increased first and then decreased. The variation trend of association degree with different administration dose and the shared peak were basically consistent, but the association of peak 29 with AST increased first and then decreased, and the association with ALT gradually decreased. The order of association among the three dosages (9.26,4.63, 1.54 g·kg-1) was inconsistent, the association orders of AST for the top 15 chromatographic peaks were as follows: 54>32>40>29(aurantio-obtusin)>42>37>56>62>33>60(chrysophanol)>24>27>52>36(rhein)>63(physcion), 29>32>40>54>42>37>56>62>33>60>24>52>27>36>63, 29>54>32>40>42>37>56>62>33>60>24>27>52>36>63. The association orders of ALT for the top 15 chromatographic peaks were as follows: 32>42>40>37>54>56>62>29>33>60>24>52>27>36>63, 29>54>32>40>42>37>56>62>33>60>24>27>52>36>63,
29>32>54>40>42>37>56>62>33>60>24>52>27>36>63. CONCLUSION The protective effect of Cassia seed dispersible tablets on acute liver injury in rats results from the synergistic or antagonistic effects between multiple active ingredients related to the administered dosage. The order of association of the chemical components that exert an effect is not the same as the dosage changes, however, the main components in the three dosage groups to exert drug efficacy are relatively consistent, The presence of this component group sets the stage for an in-depth study of Cassia seed dispersible tablets.
关键词
决明子 /
灰色关联度 /
谱效关系 /
保肝作用
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Key words
Cassia seed /
grey correlation degree /
spectral effect relationship /
hepatoprotective effect
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中图分类号：
R966
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参考文献
[1] XIA N, CHEN Y L, TAO H Y, et al. Protective effect of polysaccharides from morus nigra linn. Fruits on CCl4-induced liver damage in rats. Food Sci(食品科学), 2015, 36(13):247-251.
[2] WU S S, WANG Y, XU T, et al. Protective effect of Holboellia latifolia wall. on liver injury induced by Carbon tetrachloride in mice. J Anhui Agric Sci(安徽农业科学), 2021, 49(4):163-165, 174.
[3] DONG Y, CHEN X P, YANG H Y, et al. Hepatoprotective effects of grape seed oil on acute liver injury. Sci Technol Food Ind(食品工业科技), 2022, 43(8):342-347.
[4] LIU X D, WEN W J, ZHAO Z J. Protective effect of total flavonoids from lithocarpus polystachyus rehd. on CCl4-induced acute liver injury in mice. Her Med(医药导报), 2020, 39(12):1626-1630.
[5] FANG C Q, ZHANG W J, ZHANG J Z, et al. Research status of the construction and application of common liver injury animal models. Chin J Clin Pharmacol(中国临床药理学杂志), 2022, 38(3):276-280.
[6] HU F X. The changes and clinical significance of Th17, Treg and CTL in peripheral blood of the patients with HBV-associated subacute-on-chronic liver failure . Suzhou: Soochow University, 2012.
[7] Ch.P(2020) VolⅠ(中国药典2020年版. 一部) . 2020:151-152.
[8] YU F, SUN L, XU L J, et al. Research progress on modern application of cassia semen. Mod Chin Med(中国现代中药), 2018, 20(5):626-630.
[9] PU J W, YANG X, WU Y, et al. Protective effect of total anthraquinone in semen cassia on acute liver injury induced by LPS in rats and its mechanism. China J Mod Med(中国现代医学杂志), 2020, 30(20):6-11.
[10] WAN M. Determination of several components in raw and fried cassia seed and comparative study on their liver protecting effects. Shenyang: Liaoning University of Traditional Chinese Medicine, 2018.
[11] ZHANG B, XIE Y L. Protective Effects of total anthraquinone derived from cassia semen on immunological liver injury. J Beihua University Nat Sci, 2018, 19(6):741-744.
[12] YAN H Y, ZOU C C. Progress and prospect of application of traditional Chinese medicine fingerprint (specific chromatogram) in Chinese Pharmacopoeia (2010-2020). J South Med Univ(南方医科大学学报), 2022, 42(1):150-155.
[13] ZHU B, LI Y, HU T, et al. The hepatoprotective effect of polysaccharides from pleurotus ostreatus on carbon tetrachloride-induced acute liver injury rats. Int J Biol Macromol, 2019, 131:1-9.
[14] WANG Y F, ZHANG K F, ZHOU Y Q, et al. Protective effect and related mechanism of total flavonoids from marchantia convoluta on acute hepatic injury induced by carbon tetrachloride in rats. Lishizhen Med Mater Med Res(时珍国医国药), 2017, 28(2):277-279.
[15] LIU W, ZHANG Y N, PEI J, et al. Grey relational analysis of the relationship between variety and quality of Radix Cyathulae. Chin Pharm J(中国药学杂志), 2014, 49(20):1796-1801.
[16] WEI M L, ZOU C C, YAN H Y, et al. The mean value calculation method of Deng′s correlation degree on spectrum effect relationship of different doses of Fructus Trichosanthis dropping pills. Anhui Med J (安徽医学), 2019, 40(4):351-355.
[17] SHUI N X, DONG T H, SHA Z. On several theoretical problems of grey correlation degree. Syst Eng (系统工程), 1992, 10(6):23-26.
[18] ZOU C C, YAN H Y, WANG L L, et al. Screening and validation of antithrombotic effective components group from trichosanthes extract. Acta Pharm Sin(药学学报), 2019, 54(3):502-509.
[19] DENG J L. Basic Nethod of Grey System(灰色系统基本方法). Wuhan: Huazhong University of Science & Technology Press, 1987.
[20] MENG Y, LIU Y, FANG N, et al. Hepatoprotective effects of cassia semen ethanol extract on non-alcoholic fatty liver disease in experimental rat. Pharm Biol, 2019, 57(1):98-104.
[21] LI X E, GUO B J. Effect of cassia seeds protein and anthraquinone glycoside on blood fat of rats with hyperlipemia . Chin J Clin Rehabil(中国临床康复), 2004, 8(18):3694-3695.
[22] YANG B, REN J, QIN K M, et al. Research progress on pharmacological action and mechanism of cassia seed. J Chin Med Mater(中药材), 2018, 41(5):1247-1251.
[23] SONG P F, PAN Q S, YANG L. Biomarkers of drug-induced Liver Injury . World Chin Med(世界中医药), 2020, 15(23):3553-3560.
[24] MA J Q, GONG H B, LI E, et al. Study on the protective effects of beet extract and beet-schisandra extract compound on CCl4-induced liver injury . Pharm Today(今日药学), 2021, 31(6):409-415, 469.
[25] WEI Q, LIU K M. Research progress on spectrum-effect relationship of traditional Chinese medicine. Tradit Chin Drug Res Clin Pharmacol(中药新药与临床药理), 2019, 30(5):634-638.
[26] YAN H Y, ZOU C C, WEI M L, et al. Spectrum-effect relationship of gua lou xie bai dropping pills on myocardial ischemia. J Chin Med Mater(中药材), 2015, 38(9):1912-1918.
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脚注
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基金
安徽高校省级自然科学研究重大项目资助(KJ2016SD60),2021年安徽省大学生创新创业训练计划项目资助(S202110368104,S202110368098),2022年皖南医学院大学生科研资助项目(WK2022XS19)
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