IL －6／STAT3信号通路在脓毒症早期大鼠下丘脑－垂体－肾上腺轴中的表达及意义

摘要

Objective To explore the inner link between interleukin -6 ( IL -6 )/signal transducer and activator of transcription 3 ( STAT3 ) signaling pathway and hypothalamus -pituitary -adrenal axis ( HPAA) excessive activation in the early stage of sepsis rats .Methods Twenty -four adult male Wistar rats were randomly divided into Control group ( n=8 ) , sham-operated group ( n=8) and CLP group (n=8).The septic rat models were challenged by CLP , executed after 6 hours, the hypothalamus, pituitary and adrenal gland was isolated .Expression levels of CRH, IL-6, STAT3 and SOCS3 mRNA in hypothalamus , POMC, IL-6, STAT3 and SOCS3 mRNA in pituitary and IL -6, STAT3 and SOCS3 mRNA in adrenal gland were quantified by real -time quantitative PCR ( RT -PCR).Results Compared to Control group and Sham group: CRH, IL -6, STAT3 and SOCS3 mRNA expression levels were up -regulated significantly (P<0.01) in the hypothalamus tissues of CLP group;POMC, IL-6, STAT3 and SOCS3 mRNA expression levels were up -regulated significantly (P<0.01) in the pituitary tissues of CLP group; IL-6, STAT3 and SOCS3 mRNA expression levels were up-regulated significantly (P<0.01) in adrenal gland tissues of CLP group .Expression levels of all purpose gene were not different in Control group and Sham group .Conclusion IL -6/STAT3 signaling pathway has a close relationship with HPAA excessive activation in the early stage of sepsis rats.IL-6/STAT3 signaling pathway may be regarded as a novel therapeutic target for HPAA excessive activation of the sepsis .%目的：探讨大鼠脓毒症早期出现的HPA轴过度激活与IL－6／STAT3信号通路的内在联系。方法24只健康雄性Wistar大鼠，随机分为正常对照组（ Control组）、假手术组（ Sham组）、模型组（CLP组）三组。采用盲肠结扎穿孔（CLP）法建立脓毒症模型，术后6 h处死，分离出下丘脑、垂体、肾上腺组织。 RT－PCR检测下丘脑组织CRH、IL－6、STAT3、SOCS3 mRNA水平，垂体组织阿片促黑色素原（ POMC）、IL－6、STAT3、SOCS3 mRNA水平，肾上腺组织 IL－6、STAT3、SOCS3 mRNA水平。结果 CLP组较Control组、Sham组下丘脑组织中CRH、IL－6、STAT3、SOCS3 mRNA表达水平明显增加（P＜0.01），垂体组织中POMC、IL－6、STAT3、SOCS3 mRNA表达水平明显增加（P＜0.01），肾上腺组织中IL－6、STAT3、SOCS3 mRNA表达水平明显增加（P＜0.01）。Control组与Sham组各指标比较差异无统计学意义。结论脓毒症早期出现的HPA轴过度激活与IL－6／STAT3信号通路有着密切联系。针对IL－6／STAT3信号通路这一靶点进行干预，有望改善脓毒症状态下HPA轴的过度激活，为脓毒症的治疗提供新的思路。