化瘀通阳方对溃疡性结肠炎大鼠IL-23/JAK-STAT信号通路的影响

Effects of Stasis-resolving Yang-activating Prescription on IL-23/JAK-STAT Signaling Pathway in UC Rats

目的:观察化瘀通阳方对溃疡性结肠炎大鼠白细胞介素23(interleukin-23,IL-23)/非受体酪氨酸激酶-信号转导蛋白及转录激活因子(janus kinase-signal-transducer and activator of transcription,JAK-STAT)信号通路的影响。方法:将32只健康Wistar大鼠随机选取8只设为空白对照组,剩余24只大鼠分为模型复制组并采用5%葡聚糖硫酸钠(dectran sodium sulfate,DSS)溶液灌胃结合自由饮用,7天后随机处死其中6只大鼠及空白对照组2只大鼠,剖取结肠组织观察造模是否成功。造模成功后第2天将模型复制组18只大鼠按照随机数字表法分为模型组、化瘀通阳组和美沙拉嗪组,每组6只;未加干预的6只大鼠为空白对照组。空白对照组和模型组大鼠给予生理盐水灌肠,化瘀通阳组大鼠给化瘀通阳方剂灌肠,美沙拉嗪组大鼠给予美沙拉嗪灌肠液灌肠,各组大鼠灌肠均持续10天,每天1次。10天后,比较4组大鼠结肠长度及病理情况,观察结肠组织IL-23、JAK激酶1(janus kinase 1,JAK1)、酪氨酸激酶2(tyrosine kinase 2,TYK2)、信号转导子和转录激活子1(signal transducer and activator of transcription 1,STAT1)、信号转导子和转录激活子4(signal transducer and activator of transcription 4,STAT4)]的表达。结果:与模型组比较,化瘀通阳组和美沙拉嗪组大鼠结肠长度及病理切片显示炎症情况均显著改善(P<0.01);与模型组大鼠比较,化瘀通阳组和美沙拉嗪组大鼠结肠组织中IL-23、JAK1、STAT1、STAT4含量均降低,但两组间比较差异无统计学意义(P>0.05);TYK2各组间无明显差异(P>0.05)。结论:化瘀通阳方治疗溃疡性结肠炎的作用机制可能是通过抑制IL-23/JAK-STAT信号通路的激活、减少其他炎性因子的产生、缓解肠道炎症反应、改善肠黏膜受损情况、恢复肠道功能而实现的。

Objective:To observe the effects of stasis-resolving yang-activating prescription on IL-23/JAKSTAT signaling pathway in rats with ulcerative colitis(UC).Methods:Eight rats were chosen from 32 healthy Wistar rats and set as blank control group,the remaining 24 rats were built as model replication group,they were given 5%dectran sodium sulfate(DSS)solution by gavage and free drinking,six rats in model replication group and two in blank control group were randomly sacrificed in seven days,the colon tissue was dissected to observe whether the model was successful.On the second day after successful modeling,18 rats in the model replication group were allocated to the model group,stasis-resolving yang-activating group and mesalazine group according to random number table method,six rats in each group;six rats without intervention were selected as blank control group.Blank control group and the model group accepted physiological saline enema,stasis-resolving yangactivating group stasis-resolving yang-activating prescription enema and mesalazine group mesalazine enema,the rats in different groups accepted enema for ten days consecutively,once each day.To compare colon length and pathological conditions between four groups in ten days,to observe the expressions of IL-23,JAK1,TYK2,STAT1 and STAT4 in colon tissue.Results:Compared with the model group,colon length and pathological section in stasis-resolving yang-activating group and mesalazine group displayed that the inflammation was significantly improved(P<0.01);compared with the rats in the model group,the contents of IL-23,JAK1,STAT1 and STAT4 reduced in colon tissue of stasis-resolving yang-activating group and mesalazine group,and the difference had no statistical meaning between both groups(P>0.05);no significant difference has been found in the contents of TYK2 between different groups(P>0.05).Conclusion:The mechanism of stasis-resolving yang-activating prescription in treating UC could alleviate intestinal inflammatory response,improve intestinal mucosal damage and recover intestinal function,which might be through inhibiting the activation of IL-23/JAK-STAT signaling pathway and reducing the production of other inflammatory factors.