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研究

Protective Effect of Cassia Seed Dispersible Tablets on Acute Liver Injury in Rats and Its Spectrum Effect Relationship

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。

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.