Effect of Fuzheng Huayu Capsule on Experimental Non-alcoholic Fatty Liver Fibrosis in Mice

Xin XIN; Bei-yu CAI; Cheng CHEN; Xin WANG; Zi-ming AN; Chang-qing ZHAO; Ping LIU; Yi-yang HU; Qin FENG

doi:10.13422/j.cnki.syfjx.20210202

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Effect of Fuzheng Huayu Capsule on Experimental Non-alcoholic Fatty Liver Fibrosis in Mice

Pharmacology | 更新时间：2021-03-05

- Effect of Fuzheng Huayu Capsule on Experimental Non-alcoholic Fatty Liver Fibrosis in Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 6, Pages: 37-45(2021)
- 作者机构：
  
  1.上海中医药大学附属曙光医院，上海 201203
  2.上海中医药大学肝病研究所，上海市中医临床重点实验室，肝肾疾病病证教育部重点实验室，上海 201203
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20210202
  CLC： R2-0;R22;R285.5
- Received：20 October 2020，
  
  Published Online：22 January 2021，
  
  Published：20 March 2021
- 稿件说明：
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辛鑫,蔡蓓玉,陈成等.扶正化瘀胶囊对非酒精性脂肪性肝纤维化小鼠的影响[J].中国实验方剂学杂志,2021,27(06):37-45.

XIN Xin,CAI Bei-yu,CHEN Cheng,et al.Effect of Fuzheng Huayu Capsule on Experimental Non-alcoholic Fatty Liver Fibrosis in Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(06):37-45.
辛鑫,蔡蓓玉,陈成等.扶正化瘀胶囊对非酒精性脂肪性肝纤维化小鼠的影响[J].中国实验方剂学杂志,2021,27(06):37-45. DOI： 10.13422/j.cnki.syfjx.20210202.

XIN Xin,CAI Bei-yu,CHEN Cheng,et al.Effect of Fuzheng Huayu Capsule on Experimental Non-alcoholic Fatty Liver Fibrosis in Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(06):37-45. DOI： 10.13422/j.cnki.syfjx.20210202.

摘要

目的

探讨扶正化瘀胶囊对高反式脂肪酸高糖饮食诱导小鼠非酒精性脂肪性肝纤维化的治疗作用。

方法

采用40只SPF级雄性C57/B6小鼠随机分成4组，分别为正常组、模型组、扶正化瘀胶囊组、扶正化瘀胶囊组，每组10只，除正常组10只外，余30只用高脂高糖饮食诱导小鼠非酒精性脂肪性肝纤维化模型24周。在造模第25周起，4组分别灌胃给药4周，1次/d，扶正化瘀胶囊组4.8 g·kg

-1

；奥贝胆酸组10 mg·kg

-1

；模型组、正常组同体积生理盐水灌胃。第28周结束后收集肝组织和血清样本。分别采用苏木素-伊红（HE）染色观察各组小鼠肝组织病理变化、天狼猩红染色观察肝纤维化程度、油红O染色观察脂质沉积程度，碱水解法测定肝组织羟脯胺酸（Hyp）含量，酶法检测肝组织甘油三酯（TG）含量的变化，试剂盒法检测血清丙氨酸氨基转移酶（ALT），天门冬氨酸氨基转移酶（AST）活性及空腹血糖（FBG），酶联免疫吸附测定（ELISA）技术检测空腹胰岛素（INS）水平，并计算胰岛素抵抗指数（HOMA-IR）的变化，实时荧光定量聚合酶链式反应（Real-time PCR），蛋白免疫印迹法（Western blot）和免疫组化检测肝纤维化相关mRNA与蛋白水平的变化。

结果

与正常组比较，模型组肝组织出现显著的胶原纤维沉积、纤维化分期大多为F2-F3期，肝组织炎性灶数目增多、肝细胞气球样变和肝细胞脂肪变性明显，肝组织Hyp，TG含量显著升高（

0.01），血清ALT，AST活性及FBG，INS，HOMA-IR水平显著升高（

0.01），肝组织Ⅰ型胶原蛋白（Col-Ⅰ），Col-Ⅳ，

-平滑肌肌动蛋白（

-SMA），转化生长因子-

（TGF-

）蛋白及mRNA表达水平明显升高（

0.05，

0.01）。与模型组比较，扶正化瘀胶囊组小鼠肝组织胶原纤维沉积显著减轻，纤维化分期大多为F0-F1期，肝细胞气球样变显著改善，小叶内炎性灶数目明显减少（

0.05，

0.01）；与模型组比较，扶正化瘀胶囊可显著降低小鼠肝组织Hyp含量、血清ALT，AST水平及Col-Ⅰ，Col-Ⅳ，

-SMA，TGF-

mRNA与蛋白表达（

0.05，

0.01）。

结论

扶正化瘀胶囊对高反式脂肪酸高糖饮食诱导的小鼠非酒精性脂肪性肝纤维化具有良好的治疗作用。

Abstract

Objective

To explore the therapeutic effect of Fuzheng Huayu capsule on nonalcoholic fatty liver fibrosis induced by high trans fatty acid and high sugar diet in mice.

Method

Forty SPF male C57/B6 mice were randomly divided into 4 groups （normal group， model group， Obelcholinic acid group， and Fuzheng Huayu capsule group）， with 10 mice in each group. Except 10 mice in the normal group， nonalcoholic fatty liver fibrosis was induced by high-fat and high-sugar diet for 24 weeks in the other 30 mice. From the 25th week of modeling， 4 groups received intragastric administration for 4 weeks， once a day： Fuzheng Huayu capsule group 4.8 g·kg

-1

. Oxycholic acid group 10 mg·kg

-1

. Model control group and normal group received the same volume of normal saline. Liver tissue and serum samples were collected at the end of the 28th week. The pathological changes of liver tissue of mice in each group were observed by hematoxylin-eosin （HE） staining， the degree of liver fibrosis was observed by Sirius red staining， the degree of lipid deposition was observed by oil red O staining， the content of hydroxypropylamine （Hyp） in liver tissue was determined by alkaline hydrolysis， and the change of triglyceride （TG） in liver tissue was detected by enzyme method. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST） activities and fasting blood glucose （FBG） were detected by kit method， enzyme-linked immunosorbent assay （ELISA） was used to detect fasting Insulin （INS） level and calculate the changes of insulin resistance index （HOMA-IR）， liver fibrosis related mRNA and proteins of were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， Western blot and Immunohistochemistry.

Result

Compared with the normal group， the liver tissue in the model group showed significant collagen fiber deposition， at mostly F2-F3 fibrosis stages， with increased number of inflammatory foci in liver tissue， obvious balloon degeneration and fatty degeneration of liver cells， significantly increased contents of Hyp and TG in liver tissue （

0.01）， significantly increased activities of ALT and AST in serum and levels of FBG， INS and HOMA-IR （

0.01）， and increased type I collagen （Col-Ⅰ）， Col-Ⅳ，

-smooth muscle agonist protein （

-SMA） and transforming growth factor-

（TGF-

） protein and mRNA in liver tissue. Compared with the model group， the collagen fiber deposition in liver tissue of mice in Fuzheng Huayu capsule group was significantly reduced， at mostly F0-F1 fibrosis stages， with significantly improved balloon-like change of hepatocytes， and significantly reduced number of inflammatory foci in lobules （

0.05，

0.01）. Compared with the model group， Fuzheng Huayu capsule can significantly reduce the content of Hyp in liver tissue， the levels of serum ALT and AST， and the expression of Col-Ⅰ， Col-Ⅳ，

-SMA and TGF-

genes and proteins in mice （

0.05，

0.01）.

Conclusion

Fuzheng Huayu capsule has a good therapeutic effect on nonalcoholic fatty liver fibrosis induced by high trans fatty acid and high sugar diet in mice.

关键词

Keywords

references

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