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. 2020 Feb 29;40(2):196-202.
doi: 10.12122/j.issn.1673-4254.2020.02.10.

[Mechanism of Jiawei Huangqin decoction for treating ulcerative colitis in mice: the role of STAT3/NF-kB/IL-6 pathway]

[Article in Chinese]
Kang Wang  1 , Zhiwei Miao  2 , Yun Dong  3 , Bai Ye  1
Affiliations

[Mechanism of Jiawei Huangqin decoction for treating ulcerative colitis in mice: the role of STAT3/NF-kB/IL-6 pathway]

[Article in Chinese]
Kang Wang et al. Nan Fang Yi Ke Da Xue Xue Bao. .

Abstract
in English, Chinese

Objective: To investigate the therapeutic effect of Jiawei Huangqin (JWHQ) decoction on ulcerative colitis (UC) and the regulation of STAT3/NF-kB/IL-6 pathway.

Methods: Forty-eight mice were randomized into blank control group, model group, positive control (Sulfasalazine) group, and low-, moderate- and high-dose JWHQ Decoction groups (n=8). In all but the blank control groups, the mice were given 3% DSS in drinking water to induce UC, followed 7 days later by treatment with saline (blank control and model groups) or JWHQ Decoction by gavage (10 mL/k) for 7 consecutive days. After the treatment, the mice were euthanized and the colon length was measured and the histopathological changes were observed with HE staining. The expression levels of STAT3, NF-κB, and IL-6 in the colon tissues were detected with RT-qPCR and Western blotting.

Results: Compared with those in the blank control group, the colon length was significantly shortened and the pathological score of the colon tissue was significantly higher in all the other 5 groups (P < 0.05). Compared with those in the model group, the colon length was significantly longer and the pathological scores were obviously reduced in all the 4 treatment groups (P < 0.05). JWHQ Decoction at the high dose produced significantly better therapeutic effects than the positive drug in terms of the colon length (P < 0.05) and the colon histopathological score (P < 0.05); high-dose JWHQ Decoction also showed better effect than the other two doses (P < 0.05), whose effects were comparable (P > 0.05). The mouse models of UC showed significantly increased expression levels of STAT3, NF-κB, and IL-6 in the colon tissue (P < 0.01), which were obviously lowered by the positive drug and JWHQ Decoction (P < 0.01), especially at the high dose (P < 0.01). JWHQ Decoction at the moderate dose produced similar effects with the positive drug on STAT3, NF-kB and IL-6 levels (P > 0.05), and their effects were stronger than those of low-dose JWHQ Decoction (P < 0.05).

Conclusions: JWHQ Decoction can improve UC in mice possibly by down-regulating the expression of STAT3, NF-kB and IL-6 in colonic tissue to affect the STAT3/NF-kB/IL-6 pathway.

目的: 探讨加味黄芩汤对溃疡性结肠炎的治疗效果及对STAT3/NF-kB/IL-6通路的调控作用。

方法: 将48只小鼠随机分为空白组、模型组、阳性药物组（柳氮磺吡啶）、中药低剂量组、中药中剂量组、中药高剂量组，8只/组，按照3% DSS造模法对除空白组以外的5组小鼠进行溃疡性结肠炎造模，造模7 d后，空白组和模型组以生理盐水灌胃，药物治疗组以相应的药物灌胃，灌胃量均为10 ml/kg，共持续1周。治疗结束后，使用颈椎脱臼法处死小鼠，测量结肠长度，通过HE染色法观察各组小鼠结肠组织形态变化及结肠组织病理学评分变化，通过RT-qPCR法和Western blot法检测各组小鼠结肠组织STAT3、NF-kB、IL-6 mRNA及蛋白表达水平变化。

结果: 与空白组相比，模型组、阳性药物组及中药各剂量组小鼠结肠长度明显缩短（P < 0.05），结肠组织病理评分均明显升高（P < 0.05）；与模型组相比，阳性药物组及中药各剂量组小鼠结肠长度明显延长（P < 0.05），结肠组织病理评分均明显降低（P < 0.05）；与阳性药物组相比，中药高剂量组小鼠结肠长度明显延长（P < 0.05），结肠组织病理评分均明显降低（P < 0.05），中药中剂量组结肠长度及结肠组织病理评分均无明显差异（P > 0.05）、中药低剂量组结肠长度明显缩短（P < 0.05），结肠组织病理评分均明显增加（P < 0.05）；与中药高剂量组相比，中药中、低剂量组小鼠结肠长度均明显缩短（P < 0.05），结肠组织病理评分均明显增加（P < 0.05）；与中药中剂量组相比，中药低剂量组小鼠结肠长度均明显缩短（P < 0.05），结肠组织病理评分均明显增加（P < 0.05）。与空白组相比，模型组结肠组织STAT3、NF-kB、IL-6 mRNA及蛋白表达水平明显升高（P < 0.01），与模型组相比，阳性药物组及中药各剂量组结肠组织STAT3、NF-kB、IL-6 mRNA及蛋白表达水平明显降低（P < 0.01），其中中药高剂量组结肠组织STAT3、NF-kB、IL-6 mRNA及蛋白表达水平明显低于阳性药物组及中药中、低剂量组（P < 0.05）。而中药中剂量组结肠组织STAT3、NF-kB、IL-6 mRNA及蛋白表达水平与阳性药物组无明显差异（P > 0.05），但明显低于中药低剂量组（P < 0.05）。

结论: 加味黄芩汤对溃疡性结肠炎具有一定的改善作用，其作用机制可能与通过影响STAT3/NF-kB/IL-6通路下调结肠组织STAT3、NF-kB、IL-6表达有关。

Keywords: Jiawei Huangqin decoction; STAT3; interleukin-6; nuclear factor-κB; ulcerative colitis.

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Figures

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各组小鼠结肠组织HE染色结果的比较 HE staining of the colon tissues in each group (Original magnification: ×200). A: Blank group; B: Model group; C: Positive drug group; D, E, F: High-, moderate- and low-dose Jiawei Huangqin (JWHQ) decoction groups, respectively.
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各组小鼠结肠长度的比较 Comparison of colon length among the groups. A: Blank group; B: Model group; C: Positive drug group; D, E, F: High-, moderate- and low-dose JWHQ Decoction groups, respectively.
3
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各组小鼠结肠组织STAT3、NF-kB、IL-6 mRNA表达水平 Expression levels of STAT3, NF KB and IL-6 mRNA in the colon tissues of the mice. Compared with the blank group, **P < 0.01; compared with the model group, ##P < 0.01. A: Blank group; B: Model group; C: Positive drug group; D: High dose group of Jiawei Huangqin decoction; E: Middle dose group of Jiawei Huangqin decoction; F: Low dose group of Jiawei Huangqin decoction.
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各组小鼠结肠组织STAT3、NF-kB、IL-6蛋白表达水平 Expression levels of STAT3, NF KB and IL-6 proteins in the colon tissues of the mice. Compared with the blank group, *P < 0.01; compared with the model group, #P < 0.01. A: Blank group; B: Model group; C: Positive drug group; D, E, F: High-, moderate- and low-dose Jiawei Huangqin decoction groups, respectively.
See this image and copyright information in PMC

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