Effect of <italic style="font-style: italic">Biejiajian Pills</italic> （鳖甲煎丸） on IL-6/STAT3 Signal Pathway in Liver Tissue of Diethylnitrosamine Rat Models of Liver Precancerous Lesion Model Rats

Weicong CHEN; Bin WEN; Haitao SUN; Jialing SUN; Xuemei YANG; Shaohui HUANG; Haiyan AN; Jie PANG; Songqi HE

doi:10.13288/j.11-2166/r.2021.19.012

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Effect of Biejiajian Pills （鳖甲煎丸） on IL-6/STAT3 Signal Pathway in Liver Tissue of Diethylnitrosamine Rat Models of Liver Precancerous Lesion Model Rats

更新时间：2021-10-12

- Effect of Biejiajian Pills （鳖甲煎丸） on IL-6/STAT3 Signal Pathway in Liver Tissue of Diethylnitrosamine Rat Models of Liver Precancerous Lesion Model Rats
- Journal of Traditional Chinese Medicine Vol. 62, Issue 19, Pages: 1720-1727(2021)
- 作者机构：
  
  1.南方医科大学中医药学院，广东省广州市广州大道北1838号，510515
  2.中国人民解放军南部战区空军医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2021.19.012
  CLC：
- Received：24 March 2021，
  
  Revised：2021-07-25，
  
  Published：02 October 2021
- 稿件说明：
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陈炜聪,文彬,孙海涛等.鳖甲煎丸对二乙基亚硝胺诱导的肝癌前病变模型大鼠肝组织IL-6/STAT3信号通路的影响[J].中医杂志,2021,62(19):1720-1727.

CHEN Weicong,WEN Bin,SUN Haitao,et al.Effect of Biejiajian Pills （鳖甲煎丸） on IL-6/STAT3 Signal Pathway in Liver Tissue of Diethylnitrosamine Rat Models of Liver Precancerous Lesion Model Rats[J].Journal of Traditional Chinese Medicine,2021,62(19):1720-1727.
陈炜聪,文彬,孙海涛等.鳖甲煎丸对二乙基亚硝胺诱导的肝癌前病变模型大鼠肝组织IL-6/STAT3信号通路的影响[J].中医杂志,2021,62(19):1720-1727. DOI： 10.13288/j.11-2166/r.2021.19.012.

CHEN Weicong,WEN Bin,SUN Haitao,et al.Effect of Biejiajian Pills （鳖甲煎丸） on IL-6/STAT3 Signal Pathway in Liver Tissue of Diethylnitrosamine Rat Models of Liver Precancerous Lesion Model Rats[J].Journal of Traditional Chinese Medicine,2021,62(19):1720-1727. DOI： 10.13288/j.11-2166/r.2021.19.012.

摘要

目的

探讨鳖甲煎丸治疗肝癌前病变的可能作用机制。

方法

30只雄性Wistar大鼠随机分为正常组、模型组、鳖甲煎丸组，每组10只。除正常组外其余两组注射二乙基亚硝胺（DEN）连续16周建立肝癌前病变模型。造模第8周，鳖甲煎丸组给予鳖甲煎丸药液1.1 g/kg灌胃，正常组和模型组予以10 ml/kg生理盐水灌胃，均每日1次，连续灌胃至第18周。给药结束后测量大鼠体重、肝脏重量、肝脏表面结节数量及最大结节直径，观察肝脏病理改变及肝组织甲胎蛋白（AFP）、人胎盘型谷胱甘肽S-转移酶（GST-π）表达情况，检测肝功能指标包括丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）、总胆红素（TBiL）、白蛋白（ALB）、谷氨酰转肽酶（GGT）、碱性磷酸酶（ALP），血清白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、趋化因子2（CCL-2）表达，肝组织IL-6、TNF-α、CCL-2 mRNA表达及IL-6、TNF-α、磷酸化转录激活因子3（p-STAT3）蛋白表达。

结果

与正常组比较，模型组大鼠体重明显降低，肝脏重量及肝脏体重比均明显增加，肝脏表面结节数量及结节最大直径明显增加，HE染色见肿瘤病灶内出现大片肝细胞坏死，肿瘤细胞异型性明显，不典型增生结节内GST-π呈强阳性，瘤组织中AFP染色明显，肝功能指标除ALB外均明显升高，血清IL-6、CCL-2水平，肝组织IL-6、CCL-2mRNA表达及IL-6、TNF-α、p-STAT3蛋白相对表达量均明显升高（

＜0.01）；与模型组比较，鳖甲煎丸组肝脏重量、肝脏体重比均明显下降，肝脏表面结节数量及结节最大直径明显降低，癌细胞多呈高分化，肿瘤坏死区少见，GST-

、AFP染色较浅，阳性区域较少，血清AST、TBiL、GGT水平明显降低，血清IL-6、CCL-2水平，肝组织IL-6、CCL-2 mRNA表达及IL-6、p-STAT3蛋白相对表达量均明显降低（

＜0.05或

＜0.01）。

结论

鳖甲煎丸可能通过降低炎症因子表达，抑制IL-6/STAT3通路的激活，从而抑制肝癌前病变的发生发展。

Abstract

Objective

To explore the possible mechanism of

Biejiajian Pills

（鳖甲煎丸） in the treatment of precancerous lesions of liver.

Methods

Thirty male Wistar rats were randomly divided into normal group， model group， and

Biejiajian Pills

group， with 10 rats in each group. Except for the normal group， the rats in the other two groups were injected with diethylnitrosamine （DEN） for 16 consecutive weeks to establish liver precancerous lesion models. On the 8th week of modelling， the liquid of

Biejiajian Pills （

1.1 g/kg） was given by gavage to the

Beijiajian Pills

group， while normal saline （10 ml/kg） was administered by gavage in the normal group and the model group； the interventions were all given once daily until Week 18. After the administration， the body weight of the rats， the weight of the liver， the number of nodules on the liver surface and the largest nodule diameter were measured； the pathological changes of the liver and the expression of alpha-fetoprotein （AFP） and human placental glutathione S-transferase （GST-π） in the liver tissue were assessed； the levels of liver function indicators including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBiL）， albumin （ALB）， glutamyl transfer Peptidase （GGT）， alkaline phosphatase （ALP）， serum interleukin 6 （IL-6）， tumor necrosis factor α （TNF-α） and chemokine 2 （CCL2）， the mRNA expression of IL-6， TNF-α and CCL2， as well as the protein expression of IL-6， TNF-α and phosphorylated transcription activator 3 （p-STAT3） in the liver tissue were detected.

Results

Compared to those in the normal group， the body weight of the rats in the model group was significantly reduced； the liver weight and the ratio of liver vs body weight were significantly increased； the number of nodules on the liver surface and the largest nodule diameter were significantly increased； HE staining showed large areas of hepatocyte necrosis in the tumor lesions and obvious atypia of cancer cells； GST-π in dysplastic nodules was strongly positive； obvious AFP staining was shown in tumor tissues； all liver function indicators except for ALB were significantly increased； the serum IL-6 and CCL2 levels， the mRNA expression of IL-6 and CCL2， and the protein expression of IL-6， TNF-α， and p-STAT3 in the liver tissue were significantly increased （

＜0.01）. Compared to those in the model group， the liver weight and the ratio of liver vs body weight in the

Biejiajian Pill

group were significantly decreased； the number of nodules on the liver surface and the largest nodule diameter were significantly reduced； cancer cells were mostly highly differentiated； tumor necrosis was rare； GST-π and AFP staining were lighter， with fewer positive areas； serum AST， TBiL， and GGT levels were significantly reduced； the serum levels of IL-6 and CCL2， the expression of IL-6 and CCL2 mRNA in liver tissue and the relative expression of IL-6 and p-STAT3 protein were significantly reduced （

＜0.05 or

＜0.01）.

Conclusion

Biejiajian Pills

may inhibit the activation of IL-6/STAT3 pathway by reducing the expression of inflammatory factors， thereby inhibiting the occurrence and development of liver precancerous lesions.

关键词

Keywords

references

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Effect of Biejiajian Pills （鳖甲煎丸） on IL-6/STAT3 Signal Pathway in Liver Tissue of Diethylnitrosamine Rat Models of Liver Precancerous Lesion Model Rats

DOI：10.13288/j.11-2166/r.2021.19.012

摘要

Abstract

关键词

Keywords

references