柴胡疏肝散调控Notch通路抑制慢性脂肪性肝炎大鼠肝纤维化的研究
Effect of Chaihu Shugan Powder on Notch pathway inhibition of liver fibrosis in rats with chronic steatohepatitis
- 上海中医药杂志 2022年56卷第10期 页码：57-64
- 作者机构：
1.郑州市第六人民医院药学部（河南 郑州 450000）
2.天津大学新城医院药剂科（天津 300450）
3.郑州市第六人民医院肝病中心（河南 郑州 450000）
- 作者简介：
周淑娟，女，硕士，副主任药师，主要从事临床药学及中药药理学研究工作
李琤，副主任医师；E-mail：Leec0317@163.com
- 基金信息：
DOI：10.16305/j.1007-1334.2022.2104057
中图分类号：
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周淑娟,陈岩岩,李琤,等.柴胡疏肝散调控Notch通路抑制慢性脂肪性肝炎大鼠肝纤维化的研究[J].上海中医药杂志,2022,56(10):57-64.
ZHOU Shujuan,CHEN Yanyan,LI Cheng,et al.Effect of Chaihu Shugan Powder on Notch pathway inhibition of liver fibrosis in rats with chronic steatohepatitis[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(10):57-64.
周淑娟,陈岩岩,李琤,等.柴胡疏肝散调控Notch通路抑制慢性脂肪性肝炎大鼠肝纤维化的研究[J].上海中医药杂志,2022,56(10):57-64. DOI： 10.16305/j.1007-1334.2022.2104057.
ZHOU Shujuan,CHEN Yanyan,LI Cheng,et al.Effect of Chaihu Shugan Powder on Notch pathway inhibition of liver fibrosis in rats with chronic steatohepatitis[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(10):57-64. DOI： 10.16305/j.1007-1334.2022.2104057.
摘要
目的,2,观察柴胡疏肝散对慢性脂肪性肝炎大鼠肝纤维化病变的抑制作用，并探讨其对肝组织Notch通路的调控作用。,方法,2,采用高脂饮食喂养50只成年SD大鼠建立慢性脂肪性肝炎模型，对建模成功者采用随机数字表分为模型组、阳性组及柴胡疏肝散低、中、高剂量组，另取8只成年SD大鼠记为正常组。阳性组予以罗格列酮2 mg/kg灌胃，柴胡疏肝散低、中、高剂量组分别予以3.15、6.30、12.60 g/kg柴胡疏肝散药液灌胃，模型组和正常组每100 g大鼠体质量予以1 mL 质量分数为0.9%的氯化钠溶液灌胃，均每天1次，持续10周。HE染色观察建模情况；ELISA法检测各组大鼠干预后血清肝功能；放射免疫法检测各组大鼠干预后血清肝纤维化指标和羟脯氨酸（Hyp）含量；改良氯胺-T法检测肝组织Hyp含量；HE染色观察各组干预后肝组织病变，天狼猩红染色观察肝纤维化病变；采用RT-qPCR法及Western blot法分别检测各组干预后肝组织转化生长因子-β1（,TGF,-,β1,）、,Notch1,、,Notch3,、发状分裂相关增强子-1（,Hes1,）、α-肌动蛋白（,α,-,SMA,）mRNA和蛋白表达。,结果,2,干预后模型组血清肝功能和肝纤维化指标、肝组织Hyp含量均高于正常组，阳性组和柴胡疏肝散低、中、高剂量组均低于模型组，柴胡疏肝散低剂量组均高于阳性组，柴胡疏肝散高剂量组均低于阳性组，上述差异均有统计学意义（,P,<,0.05）。模型组肝纤维化病变显著，阳性组和柴胡疏肝散低、中、高剂量组均减轻，且柴胡疏肝散高剂量组与正常组最为接近。模型组干预后肝组织,TGF,-,β1,、,Notch3,、,Hes1,、,α,-,SMA, mRNA及蛋白相对表达量均高于正常组，阳性组和柴胡疏肝散低、中、高剂量组均低于模型组，柴胡疏肝散低剂量组均高于阳性组，柴胡疏肝散高剂量组均低于阳性组，而,Notch1, mRNA及蛋白的变化趋势正相反，上述差异均有统计学意义（,P,<,0.05）。,结论,2,对慢性脂肪性肝炎大鼠予以柴胡疏肝散灌胃可减轻肝损害，抑制肝纤维化病变，推测与其调控Notch通路，抑制TGF-β1、Notch3、Hes1、α-SMA表达，上调Notch1表达有关。
Abstract
Objective,2,To observe the inhibitory effect of Chaihu Shugan Powder on liver fibrosis in rats with chronic steatohepatitis， and to explore its effect on the regulation of Notch pathway in liver tissues.,Methods,2,Totally 50 SD adult rats were fed with high-fat diet to establish chronic steatohepatitis in rats. The successful modelled rats were divided into model group， positive group， low， medium and high dose groups of Chaihu Shugan Powder by a random number table. Another 8 adult SD rats were recorded as normal group. The positive group was administrated with rosiglitazone 2 mg/kg， Chaihu Shugan Powder low， medium and high dose groups with 3.15， 6.30， 12.60 g/kg Chaihu Shugan Powder soup， and the model group and the normal group with 1 mL/ 100 g normal saline once a day for 10 weeks. Hematoxylin eosin （HE） staining was used to observe the modeling. The serum liver function was measured with ELISA before and after the intervention， and radioimmunoassay was used to detect the liver fibrosis indexes and contents of hydroxyproline （Hyp） after intervention. Hyp contents in liver tissues were detected by modified chloramine-T method. HE staining was used to observe the pathological changes of liver tissues. Hepatic fibrosis was observed by Sirius red staining. The mRNA and protein expressions of ,TGF,-,β1,，, Notch 1， Notch 3， ,hairy and enhancer of split 1 （,Hes1,）， α- smooth muscle actin （,α,-,SMA,） were detected by RT-qPCR and Western blot.,Results,2,The levels of serum liver function and liver fibrosis indexes， Hyp content in liver tissues of the model group after intervention were higher than those of the normal group， while those in the positive group and Chaihu Shugan Powder low， medium and high dose groups were lower than those in the model group， and the levels in the low dose group of Chaihu Shugan Powder were higher than those in the positive group， while those in the high dose group of Chaihu Shugan Powder were lower than those in the positive group. And the above differences were statistically significant （,P,<,0.05）. The pathological changes of liver fibrosis in the model group were significant， while those in the positive group and Chaihu Shugan Powder low， medium and high dose groups were alleviated， and the changes in the high dose group of Chaihu Shugan Powder were most similar to those of the normal group. After intervention， the relative expressions of ,TGF,-,β1， Notch3， Hes1， α,-,SMA, mRNAs and proteins in liver tissue in the model group were higher than those in the normal group， while those in the positive group and Chaihu Shugan Powder low， medium and high dose groups were lower than those in the model group， and those in the low dose group of Chaihu Shugan Powder were higher than those in the positive group， while the expressions in the high dose group of Chaihu Shugan Powder were lower than those in the positive group. And the changes of ,Notch 1, mRNA and protein were on the contrary. The above differences had highly statistically significant （,P,<,0.05）.,Conclusion,2,Intragastric administration of Chaihu Shugan Powder to rats with chronic steatohepatitis can alleviate liver damage and inhibit hepatic fibrosis， which may be related to the regulation of Notch pathway， inhibition of TGF-β1， Notch3， Hes1， α-SMA expression and up-regulation of Notch1 expression.
关键词
慢性肝炎脂肪肝肝纤维化柴胡疏肝散Notch通路大鼠模型中药研究
Keywords
chronic hepatitisfatty liverliver fibrosisChaihu Shugan PowderNotch pathwayrat modeltraditional Chinese herbal medicine research
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