基于IL-6/STAT3信号通路研究甘草泻心汤治疗溃疡性结肠炎的作用机制

陈浩; 徐速; 颜帅; 陈丙学; 张波; 卢芩; 孙晖; 周星鑫; 曾莉

基于IL-6/STAT3信号通路研究甘草泻心汤治疗溃疡性结肠炎的作用机制

陈浩¹,
徐速²,
颜帅³,
陈丙学⁴,
张波¹,
卢芩¹,
孙晖¹,
周星鑫¹,
曾莉^5,

1.
东南大学附属中大医院，江苏南京 210009
2.
南京中医药大学附属盐城市中医院，江苏盐城 224001
3.
苏州市中医医院肛肠科，江苏苏州 215009
4.
溧阳市中医院肛肠科，江苏溧阳 213300
5.
南京中医药大学第一临床医学院，江苏南京 210023

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出版历程
- 刊出日期: 2017-11-10

Gancao Xiexin Decoction Ameliorates TNBS/Ethanol-Induced Ulcerative Colitis in SD Rats Through Regulation of the IL-6/STAT3 Signaling Pathway

CHENHao¹,
XUSu²,
YANShuai³,
CHENBing-xue⁴,
ZHANGBo¹,
LUQin¹,
SUNHui¹,
ZHOUXing-xin¹,
ZENGLi^5
,

1.
Zhongda Hospital, Southeast University, Nanjing, 210009, China
2.
Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, 224001, China
3.
Department of Anorectal Surgery, Suzhou Hospital of Traditional Chinese Medicine, Suzhou, 215009, China
4.
Department of Anorectal Surgery, Liyang Hospital of Traditional Chinese Medicine, Liyang, 213300, China
5.
The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China

摘要

摘要: 目的观察甘草泻心汤对溃疡性结肠炎模型大鼠的疗效和IL-6/STAT3信号通路中相关分子的调节作用，以揭示其治疗溃疡性结肠炎的作用机制及安全性。方法将60只SD大鼠随机分为空白组，模型组，美沙拉嗪组，甘草泻心汤低、中、高剂量组6组。以TNBS/乙醇法造模后分别以生理盐水、美沙拉嗪及甘草泻心汤各剂量灌胃。14d后检测血清ALT、AST、BUN及Cr含量，HE染色观察结肠组织结构改变，免疫组化分析结肠组织IL-6、STAT3及磷酸化STAT3的蛋白表达，以qPCR法检测结肠组织IL-6及STAT3的mRNA表达。结果与空白组比较，模型组血清AST含量明显升高（P<0.01），而ALT、BUN、Cr无明显变化（P>0.05），结肠组织病理评分明显增加（P<0.01），结肠组织IL-6和STAT3的蛋白和mRNA表达均明显增高（P<0.01），且STAT3活化明显增加（P<0.01）。与模型组比较，甘草泻心汤各剂量组血清AST含量明显降低（P<0.01），美沙拉嗪组及甘草泻心汤中剂量组结肠组织病理评分明显降低（P<0.01），结肠组织IL-6、STAT3和磷酸化STAT3的蛋白表达明显降低（P<0.01），IL-6和STAT3的mRNA表达明显降低（P<0.01）。结论甘草泻心汤能改善溃疡性结肠炎模型大鼠结肠病理结构改变，尤以中剂量明显。其作用机制可能与降低结肠组织中IL-6水平，抑制IL-6/STAT3信号转导通路，降低STAT3表达与活化有关。甘草泻心汤对TNBS溃疡性结肠炎模型大鼠的治疗安全有效。
- 溃疡性结肠炎 /
- 甘草泻心汤 /
- 白介素-6 /
- 信号转导转录激活因子3
Abstract: OBJECTIVE To observe the curative effect of Gancao Xiexin Decoction(GCXXT) on ulcerative colitis (UC) model rats and explore the regulation mechanism of related molecules in the pathways of IL-6/STAT3. METHODS 60 SD rats were randomly divided into 6 groups: control， TNBS/ethanol， mesalazine and GCXXT (2.93， 5.86， 11.72g/kg) groups. Blood serum was extracted to detect the content of ALT， AST， BUN and Cr. Colon tissues were observed by optical microscope. The expressions of protein of IL-6， STAT3 and phosphate STAT3 were evaluated by immunohistochemistry. The expressions of mRNA of IL-6 and STAT3 were analyzed by qPCR. RESULTS Compared with the blank group， AST in serum of model group increased obviously (P<0.01). However， ALT， BUN and Cr displayed no change (P>0.05). Pathological scores of colon tissues of model group increased significantly (P<0.01). The expressions of protein and mRNA of IL-6 and STAT3 in colon tissues increased in model group (P<0.01). Furthermore， the activation of STAT3 increased (P<0.01). Compared with the model group， AST in serum of rats of three groups treated with GCXXT decreased (P<0.01). Pathological scores of colon tissues of mesalazine group and medium dose GCXXT group decreased significantly (P<0.01). After the treatment of mesalazine or GCXXT， the expression of protein of IL-6， STAT3 and phosphate STAT3 reduced (P<0.01). The expression of mRNA of IL-6 and STAT3 decreased (P<0.01). CONCLUSION GCXXT can alleviate the pathological changes of colon， and medium dose of it can lead to satisfactory results. The mechanism may be related to its abilities to decrease expression of IL-6 in colonic tissue， inhibit IL-6/STAT3 signaling pathway and reduce the expression and activation of STAT3. These results showed that GCXXT is effective and safe in ameliorating ulcerative colitis.
- ulcerative colitis /
- Gancao Xiexin decoction /
- interleukin-6 /
- signal transducer and activator of transcription 3

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