基于 STAT3/NF-kB/IL-6 通路研究加味黄芩汤治疗溃疡性结肠炎的作用机制

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。

Mechanism of Jiawei Huangqin decoction for treating ulcerative colitis in mice: the role ofSTAT3/NF-kB/IL-6 pathway

Objective To investigate the therapeutic effect of Jiawei Huangqin (JWHQ) decoction on ulcerative colitis (UC) andthe regulation of STAT3/NF-kB/IL-6 pathway. Methods Forty-eight mice were randomized into blank control group, modelgroup, positive control (Sulfasalazine) group, and low-, moderate- and high-dose JWHQ Decoction groups (n=8). In all but theblank control groups, the mice were given 3% DSS in drinking water to induce UC, followed 7 days later by treatment withsaline (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 HEstaining. The expression levels of STAT3, NF-κB, and IL-6 in the colon tissues were detected with RT-qPCR and Westernblotting. Results Compared with those in the blank control group, the colon length was significantly shortened and thepathological score of the colon tissue was significantly higher in all the other 5 groups (P<0.05). Compared with those in themodel group, the colon length was significantly longer and the pathological scores were obviously reduced in all the 4treatment groups (P<0.05). JWHQ Decoction at the high dose produced significantly better therapeutic effects than the positivedrug in terms of the colon length (P<0.05) and the colon histopathological score (P<0.05); high-dose JWHQ Decoction alsoshowed better effect than the other two doses (P<0.05), whose effects were comparable (P>0.05). The mouse models of UCshowed significantly increased expression levels ofSTAT3, NF-κB, and IL-6 in the colon tissue (P<0.01),which were obviously lowered by the positive drugand JWHQ Decoction (P<0.01), especially at the highdose (P<0.01). JWHQ Decoction at the moderate doseproduced 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).Conclusion JWHQ Decoction can improve UC in mice possibly by down-regulating the expression of STAT3, NF-kB and IL-6in colonic tissue to affect the STAT3/NF-kB/IL-6 pathway.