化痰活血扶正方及其拆方后的相关药组对模型大鼠肝纤维化指标的影响
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摘要
目的观察化痰活血扶正方拆方后的相关药组对肝纤维化大鼠模型肝功能及肝纤维化指标的影响,并探讨其作用机制.方法选择雄性SD大鼠120只,随机分为正常组(control)、模型组(model)、阳性药物组(Silybin)、低中高剂量化痰组(HTL、HTM、HTH)、低中高剂量活血化瘀组(HXHYL、HXHYM、HXHYH)、低中高剂量扶正组(FZL、FZM、FZH)、低中高剂量化痰活血扶正组(HTHXFZL、HTHXFZM、HTHXFZH).除正常照组外,其余各组大鼠均腹腔注射4%TAA(水为溶剂)0.05 mL/kg体重,剂量200 mg/kg,每周2次,持续8 wk.造模开始次日,各低、中、高剂量组分别按照0.25,0.5,1.0 g/kg剂量,每日1次、予10 m L/kg体重不同浓度的药物灌胃,阳性药物组给予水飞蓟宾50 mg/kg体重灌胃,每日1次,用药8 wk.观察治疗前后的肝功能[谷草转氨酶(aspartate transaminase,AST)、谷丙转氨酶(alanine transaminase,ALT)、总蛋白(total protein,TP)、AIb、GLB]、肝纤维化指标[层黏连蛋白(laminin,LN)、COL_4、透明质酸(hyaluronic acid,HA)].结果干预后,各组血清的AST、ALT均有下降,除FZL组外,其余各组与模型组相比差异均有统计学意义(P<0.05、P<0.01或P<0.001);HTM、HTHXFZH的TP与模型组相比差异有统计学意义(P<0.05或P<0.01),HTM、HTH、HXHYM、FZM、FZH、HTHXFZM、HTHXFZH的AIb与模型组相比差异均有统计学意义(P<0.05、P<0.01或P<0.001).各治疗组的LN均有下降,除HXHYM组、FZM组外,其余各组与模型组相比差异显著,均有统计学意义(P<0.05、P<0.01或P<0.001);各治疗组的COL_4均有下降,除HTL、HTH、HXHYM、HXHYH、FZL、FZH组外,其余各组与模型组相比差异显著,均有统计学意义(P<0.05或P<0.001);各治疗组的HA均有下降,其中HXHYM、FZL、HTHXFZH与模型组相比差异显著,均有统计学意义(P<0.05或P<0.01).结论化痰活血扶正方拆方后各药组可显著改善肝纤维化模型大鼠的肝功能及肝纤维化指标,减缓肝纤维化进展速度.
AIM To observe the effect of phlegm reducing, blood activating, and body resistance strengthening decoction and its decomposed formulas on liver function and hepatic fibrosis indexes in rats with liver fibrosis, and to explore the underlying mechanism.METHODS One hundred and twenty male SD rats were randomly divided into a normal group, a model group, a positive drug(silybin) group, low-, middle-, and high-dose phlegm reducing groups(HTL, HTM, and HTH), low-, middle-, and high-dose blood activating groups(HXHYL, HXHYM, and HXHYH), low-, middle-, and high-dose body resistance strengthening groups(FZL, FZM, and FZH), and low-, middle-, and high-dose phlegm reducing, blood activating, and body resistance strengthening decoction groups(HTHXFZL, HTHXFZM, and HTHXFZH). Except the normal group, the rats in the other groups were injected with 4% TAA in water at a dose of 200 mg/kg, twice a week for 8 wk. The next day after modelling, the low-, middle-, and high-dose groups were intragastrically given corresponding drugs at 0.25, 0.5, and 1.0 g/kg(once daily), respectively, and the positive drug group was given silybin 50 mg/kg body weight once daily for 8 wk. The liver function [aspartate transaminase(AST), alanine transaminase(ALT), total protein(TP), Alb, and GLB] and hepatic fibrosis indexes [laminin, COL_4, hyaluronic acid(HA)] were observed before and after treatment.RESULTS After intervention, serum AST and ALT decreased in all groups except the FZL group, and the differences between the other groups and the model group were statistically significant(P < 0.05, P < 0.01, or P < 0.001). Serum TP in the HTM and HTHXFZH groups was significantly different from that in the model group(P < 0.05 or P < 0.01). Serum Alb in the HTM, HTH, HXHYM, FZM, FZH, HTHXFZM, and HTHXFZH groups was significantly different from that in the model group(P < 0.05, P < 0.01, or P < 0.001). Serum LN decreased in each treatment group, and except the HXHYM and FZM groups, the difference between the other groups and the model group was significant(P < 0.05, P < 0.01 or P < 0.001). Serum COL_4 decreased in each treatment group, and except the HTL, HTH, HXHYM, HXHYH, FZL, and FZH groups, there was a significant difference between the other groups and the model group(P < 0.05 or P < 0.001). Serum HA decreased in each treatment group, and there was a significant difference between the HXHYM, FZL, and HTHXFZH groups and the model group(P < 0.05 or P < 0.01).CONCLUSION Phlegm reducing, blood activating, and body resistance strengthening decoction and its decomposed formulas can significantly improve liver function and liver fibrosis in rats with liver fibrosis.
AIM To observe the effect of phlegm reducing, blood activating, and body resistance strengthening decoction and its decomposed formulas on liver function and hepatic fibrosis indexes in rats with liver fibrosis, and to explore the underlying mechanism.METHODS One hundred and twenty male SD rats were randomly divided into a normal group, a model group, a positive drug(silybin) group, low-, middle-, and high-dose phlegm reducing groups(HTL, HTM, and HTH), low-, middle-, and high-dose blood activating groups(HXHYL, HXHYM, and HXHYH), low-, middle-, and high-dose body resistance strengthening groups(FZL, FZM, and FZH), and low-, middle-, and high-dose phlegm reducing, blood activating, and body resistance strengthening decoction groups(HTHXFZL, HTHXFZM, and HTHXFZH). Except the normal group, the rats in the other groups were injected with 4% TAA in water at a dose of 200 mg/kg, twice a week for 8 wk. The next day after modelling, the low-, middle-, and high-dose groups were intragastrically given corresponding drugs at 0.25, 0.5, and 1.0 g/kg(once daily), respectively, and the positive drug group was given silybin 50 mg/kg body weight once daily for 8 wk. The liver function [aspartate transaminase(AST), alanine transaminase(ALT), total protein(TP), Alb, and GLB] and hepatic fibrosis indexes [laminin, COL_4, hyaluronic acid(HA)] were observed before and after treatment.RESULTS After intervention, serum AST and ALT decreased in all groups except the FZL group, and the differences between the other groups and the model group were statistically significant(P < 0.05, P < 0.01, or P < 0.001). Serum TP in the HTM and HTHXFZH groups was significantly different from that in the model group(P < 0.05 or P < 0.01). Serum Alb in the HTM, HTH, HXHYM, FZM, FZH, HTHXFZM, and HTHXFZH groups was significantly different from that in the model group(P < 0.05, P < 0.01, or P < 0.001). Serum LN decreased in each treatment group, and except the HXHYM and FZM groups, the difference between the other groups and the model group was significant(P < 0.05, P < 0.01 or P < 0.001). Serum COL_4 decreased in each treatment group, and except the HTL, HTH, HXHYM, HXHYH, FZL, and FZH groups, there was a significant difference between the other groups and the model group(P < 0.05 or P < 0.001). Serum HA decreased in each treatment group, and there was a significant difference between the HXHYM, FZL, and HTHXFZH groups and the model group(P < 0.05 or P < 0.01).CONCLUSION Phlegm reducing, blood activating, and body resistance strengthening decoction and its decomposed formulas can significantly improve liver function and liver fibrosis in rats with liver fibrosis.
引文
1王雅君,王思鉴.抗纤丸治疗肝硬化病人抗纤维化的疗效.中国老年学杂志2016;36:3758-3759[DOI:10.3969/j.issn.1005-9202.2016.15.069]
2王统华,周喜汉,何守搞,苏建伟,蒋旗,胡高裕.安络化纤丸辅助治疗对乙型肝炎肝硬化患者血清炎性因子、肝纤维化指标及免疫功能的影响.海南医学院学报2017;23:2184-2191
3陈文龙,曹文富,何英,高世娇.不同剂量益气化瘀化痰养阴中药对肝纤维化大鼠肝组织结构及PPARγ的影响.中国老年学杂志2014;34:3369-3372[DOI:10.3969/j.issn.1005-9202.2014.12.073]
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6陈国中,徐珊,张永生,朱飞叶.化痰行瘀汤抗大鼠肝纤维化作用机制研究.浙江中医药大学学报2014;38:1369-1377
7徐学刚,黄毓,黄玉娟.益气活血解毒方治疗慢性病毒性乙型肝炎肝纤维化的临床研究.陕西中医2015;36:1450-1452[DOI:10.3969/j.issn.1000-7369.2015.11.004]
8曾文勇,石小枫,刘杞,王志毅,徐宁,张丽旦.三七总皂苷对肝纤维化大鼠胶原及TGF-β1 mRNA表达的影响.胃肠病学和肝病学杂志2010;15:795-798[DOI:10.3969/j.issn.1006-5709.2010.09.006]
9呙琳琳,戴立里,唐静.丹参素对PDGF-BB刺激下肝星状细胞的抑制作用.第三军医大学学报2011;33:1610-1614
10张巍.赤芍对肝纤维化因子ECM等的影响.临床合理用药杂志2011;9:74-75
11张晓苹,赵宏军,陈芝芸.丹参煎液对肝纤维化大鼠肝脏肾素-血管紧张素系统的影响.中国中西医结合消化杂志2010;17:102-105
12王蓉,潘沛,王杰,吴岩,原永芳.丹参多酚酸盐对肝纤维化大鼠NF-κB和κBα表达的影响.中国新药与临床杂志2011;30:51-55
13陈涛,常欣峰,尹宝,曹思,郑宝平,黄志华,韩立民.白芥子药组对TAA诱导肝纤维化模型大鼠赣功能指标的影响.赣南医学院报2017;37:38-41
14董婧婧,刘艳菊,陈祥胜,付伟,李鑫.三七粉对四氯化碳(CCl4)诱导的大鼠慢性肝损伤的保护作用.中国现代医学杂志2017;27:32-37[DOI:10.3969/j.issn.1005-8982.2017.08.007]
15李雪梅,冯琴,彭景华.苦杏仁苷对二甲基亚硝胺诱导的大鼠肝纤维化的防治作用.中西医结合肝病杂志2011;21:221-223
16吴建良,王志勇,孙丽伟,郭赟,付金龙,刘成海.冬虫夏草对肝纤维化小鼠Smad3蛋白表达的影响.中国中医急症2011;20:1786-1788[DOI:10.3969/j.issn.1004-745X.2011.11.035]
17郑保平,姚乃礼,牛阳,陶夏平.白芥子抗肝纤维化的理论探讨.时珍国医国药2011;22:2754-2755
18李成浩,张红英.黄芪提取物对四氯化碳致大鼠肝纤维化的保护作用.中国实用方剂学杂志2011;37:217-220[DOI:10.3969/j.issn.1005-9903.2011.20.061]
19蒋征奎,王学方.茯苓皮水提物对四氯化碳诱导大鼠肝纤维化的改善作用.中国药房2017;28:3065-3068[DOI:10.6039/j.issn.1001-0408.2017.22.11]
20 Abdulaziz Bardi D,Halabi MF,Abdullah NA,Rouhollahi E,Hajrezaie M,Abdulla MA.In vivo evaluation of ethanolic extract of Zingiber officinale rhizomes for its protective effect against liver cirrhosis.Biomed Res Int 2013;2013:918460[PMID:24396831 DOI:10.1155/2013/918460]
21李静,刘艳丽,李同进.中成药治疗慢性乙型肝炎肝纤维化疗效观察.中国临床医生2015;43:59-60[DOI:10.3969/j.issn.2095-8552.2015.02.018]
22曾峥,全晖,程莉惠,蔡明燕.慢性乙肝肝纤维化中血清肝纤维化指标与肝功能指标联合检测的临床应用价值.智慧健康2017;8:18-20
23刘茂希.骨桥蛋白在大鼠免疫性肝纤维化中的表达及与肝功能指标的相关性.中国图书资料2010;21:33
24陈国忠,徐珊,张永生,朱飞叶.化痰行瘀汤对肝纤维化大鼠血清肝功能及透明质酸含量的影响.浙江中医药大学学报2013;37:1236-1239[DOI:10.3969/j.issn.1005-5509.2013.10.030]
2王统华,周喜汉,何守搞,苏建伟,蒋旗,胡高裕.安络化纤丸辅助治疗对乙型肝炎肝硬化患者血清炎性因子、肝纤维化指标及免疫功能的影响.海南医学院学报2017;23:2184-2191
3陈文龙,曹文富,何英,高世娇.不同剂量益气化瘀化痰养阴中药对肝纤维化大鼠肝组织结构及PPARγ的影响.中国老年学杂志2014;34:3369-3372[DOI:10.3969/j.issn.1005-9202.2014.12.073]
4高世娇,陈文龙,何英,曹文富,赖国旗.益气化瘀化痰养阴剂对肝纤维化模型大鼠肝脏上皮间质表型的影响.中国老年学杂志2015;35:2612-2615[DOI:10.3969/j.issn.1005-9202.2015.10.007]
5陈国中,徐珊,张永生,朱飞叶.化痰行瘀汤对肝纤维化大鼠组织病理学及羟脯氨酸含量的影响.浙江医学2013;35:1498-1501
6陈国中,徐珊,张永生,朱飞叶.化痰行瘀汤抗大鼠肝纤维化作用机制研究.浙江中医药大学学报2014;38:1369-1377
7徐学刚,黄毓,黄玉娟.益气活血解毒方治疗慢性病毒性乙型肝炎肝纤维化的临床研究.陕西中医2015;36:1450-1452[DOI:10.3969/j.issn.1000-7369.2015.11.004]
8曾文勇,石小枫,刘杞,王志毅,徐宁,张丽旦.三七总皂苷对肝纤维化大鼠胶原及TGF-β1 mRNA表达的影响.胃肠病学和肝病学杂志2010;15:795-798[DOI:10.3969/j.issn.1006-5709.2010.09.006]
9呙琳琳,戴立里,唐静.丹参素对PDGF-BB刺激下肝星状细胞的抑制作用.第三军医大学学报2011;33:1610-1614
10张巍.赤芍对肝纤维化因子ECM等的影响.临床合理用药杂志2011;9:74-75
11张晓苹,赵宏军,陈芝芸.丹参煎液对肝纤维化大鼠肝脏肾素-血管紧张素系统的影响.中国中西医结合消化杂志2010;17:102-105
12王蓉,潘沛,王杰,吴岩,原永芳.丹参多酚酸盐对肝纤维化大鼠NF-κB和κBα表达的影响.中国新药与临床杂志2011;30:51-55
13陈涛,常欣峰,尹宝,曹思,郑宝平,黄志华,韩立民.白芥子药组对TAA诱导肝纤维化模型大鼠赣功能指标的影响.赣南医学院报2017;37:38-41
14董婧婧,刘艳菊,陈祥胜,付伟,李鑫.三七粉对四氯化碳(CCl4)诱导的大鼠慢性肝损伤的保护作用.中国现代医学杂志2017;27:32-37[DOI:10.3969/j.issn.1005-8982.2017.08.007]
15李雪梅,冯琴,彭景华.苦杏仁苷对二甲基亚硝胺诱导的大鼠肝纤维化的防治作用.中西医结合肝病杂志2011;21:221-223
16吴建良,王志勇,孙丽伟,郭赟,付金龙,刘成海.冬虫夏草对肝纤维化小鼠Smad3蛋白表达的影响.中国中医急症2011;20:1786-1788[DOI:10.3969/j.issn.1004-745X.2011.11.035]
17郑保平,姚乃礼,牛阳,陶夏平.白芥子抗肝纤维化的理论探讨.时珍国医国药2011;22:2754-2755
18李成浩,张红英.黄芪提取物对四氯化碳致大鼠肝纤维化的保护作用.中国实用方剂学杂志2011;37:217-220[DOI:10.3969/j.issn.1005-9903.2011.20.061]
19蒋征奎,王学方.茯苓皮水提物对四氯化碳诱导大鼠肝纤维化的改善作用.中国药房2017;28:3065-3068[DOI:10.6039/j.issn.1001-0408.2017.22.11]
20 Abdulaziz Bardi D,Halabi MF,Abdullah NA,Rouhollahi E,Hajrezaie M,Abdulla MA.In vivo evaluation of ethanolic extract of Zingiber officinale rhizomes for its protective effect against liver cirrhosis.Biomed Res Int 2013;2013:918460[PMID:24396831 DOI:10.1155/2013/918460]
21李静,刘艳丽,李同进.中成药治疗慢性乙型肝炎肝纤维化疗效观察.中国临床医生2015;43:59-60[DOI:10.3969/j.issn.2095-8552.2015.02.018]
22曾峥,全晖,程莉惠,蔡明燕.慢性乙肝肝纤维化中血清肝纤维化指标与肝功能指标联合检测的临床应用价值.智慧健康2017;8:18-20
23刘茂希.骨桥蛋白在大鼠免疫性肝纤维化中的表达及与肝功能指标的相关性.中国图书资料2010;21:33
24陈国忠,徐珊,张永生,朱飞叶.化痰行瘀汤对肝纤维化大鼠血清肝功能及透明质酸含量的影响.浙江中医药大学学报2013;37:1236-1239[DOI:10.3969/j.issn.1005-5509.2013.10.030]