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[中药汤剂治疗小鼠溃疡性结肠炎的机制:STAT3/NF-κB/IL-6信号通路的作用]

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

作者信息

Wang Kang, Miao Zhiwei, Dong Yun, Ye Bai

机构信息

Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210046, China.

Department of Gastroenterology, Zhangjiagang Hospital of Chinese Medicine, Zhangjiagang 215600, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2020 Feb 29;40(2):196-202. doi: 10.12122/j.issn.1673-4254.2020.02.10.

Abstract

OBJECTIVE

To investigate the therapeutic effect of (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 (=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 ( < 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 ( < 0.05). JWHQ Decoction at the high dose produced significantly better therapeutic effects than the positive drug in terms of the colon length ( < 0.05) and the colon histopathological score ( < 0.05); high-dose JWHQ Decoction also showed better effect than the other two doses ( < 0.05), whose effects were comparable ( > 0.05). The mouse models of UC showed significantly increased expression levels of STAT3, NF-κB, and IL-6 in the colon tissue ( < 0.01), which were obviously lowered by the positive drug and JWHQ Decoction ( < 0.01), especially at the high dose ( < 0.01). JWHQ Decoction at the moderate dose produced similar effects with the positive drug on STAT3, NF-kB and IL-6 levels ( > 0.05), and their effects were stronger than those of low-dose JWHQ Decoction ( < 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.

摘要

目的

探讨(JW HQ)汤对溃疡性结肠炎(UC)的治疗作用及对STAT3/NF-κB/IL-6信号通路的调控作用。

方法

将48只小鼠随机分为空白对照组、模型组、阳性对照组(柳氮磺胺吡啶)以及低、中、高剂量JW HQ汤组(每组 = 8只)。除空白对照组外,其余各组小鼠均饮用含3%葡聚糖硫酸钠(DSS)的水以诱导UC,7天后,空白对照组和模型组小鼠给予生理盐水,其余4组小鼠给予JW HQ汤灌胃(10 mL/kg),连续7天。治疗结束后,处死小鼠,测量结肠长度,HE染色观察组织病理学变化。采用RT-qPCR和蛋白质免疫印迹法检测结肠组织中STAT3、NF-κB和IL-6的表达水平。

结果

与空白对照组相比,其余5组小鼠结肠长度均显著缩短,结肠组织病理评分显著升高(P < 0.05)。与模型组相比,4个治疗组小鼠结肠长度均显著延长,病理评分明显降低(P < 0.05)。高剂量JW HQ汤在结肠长度(P < 0.05)和结肠组织病理评分(P < 0.05)方面的治疗效果明显优于阳性药物;高剂量JW HQ汤的效果也优于其他两个剂量组(P < 0.05),而低、中剂量组效果相当(P > 0.05)。UC小鼠模型结肠组织中STAT3、NF-κB和IL-6表达水平显著升高(P < 0.01),阳性药物和JW HQ汤可使其明显降低(P < 0.01),尤其是高剂量JW HQ汤(P < 0.01)。中剂量JW HQ汤对STAT3、NF-κB和IL-6水平的影响与阳性药物相似(P > 0.05),且其作用强于低剂量JW HQ汤(P < 0.05)。

结论

JW HQ汤可能通过下调结肠组织中STAT3、NF-κB和IL-6的表达,影响STAT3/NF-κB/IL-6信号通路,从而改善小鼠UC。

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