摘要
目的探讨右美托咪定对脓毒症致肺损伤大鼠HMGB1/TLR4/NF-κB信号通路的调控作用。方法选取30只Wistar大鼠随机分为对照组(假手术)、模型组(盲肠结扎穿孔)、右美托咪定组(盲肠结扎穿孔+右美托咪定处理),每组10只。右美托咪定组于术前30min腹腔注射40μg/kg右美托咪定,对照组和模型组腹腔注射生理盐水。造模后24h处死大鼠。苏木精-伊红染色法评估肺组织病理学变化;ELISA法检测肺组织髓过氧化物酶(myeloperoxidase,MPO)活性;计算肺组织湿干重比(W/D);western blot法检测肺组织中HMGB1、TLR4、NF-κB蛋白表达。结果与对照组相比较,模型组大鼠肺组织MPO、肺损伤评分及肺组织W/D显著增高(P<0.05);与模型组相比较,右美托咪定组大鼠肺组织MPO、肺损伤评分及肺组织W/D显著降低(P<0.05),但仍高于对照组(P<0.05)。与对照组相比较,模型组大鼠肺组织HMGB1、TLR4、NF-κB蛋白表达水平显著增高(P<0.05);与模型组相比较,右美托咪定组大鼠肺组织HMGB1、TLR4、NF-κB蛋白表达水平显著降低(P<0.05),但仍高于对照组(P<0.05)。结论右美托咪定可能通过抑制HMGB1/TLR4/NF-κB信号通路,减轻炎症反应,从而发挥对脓毒症肺损伤的保护作用。
Objective To evaluate the effect of dexmedetomidine against rat sepsis-induced lung injury by regulating HMGB1/TLR4/NF-kB signaling pathway. Methods 30 Wistar rats were randomly divided into thecontrol group （sham-operation） , the model group （cecal ligation and puncture） and the dexmedetomidine group （ ce-cal ligation and puncture ＋ dexmedetomidine treatment） , 10 rats in each group. 30min before operation, the dexme-detomidine group was intraperitoneal？ injected with 40jjig/kg dexmedetomidine, and the control group and model group were intraperitoneal？ injected with normal saline. 24 hours after modeling, pulmonary pathological changes were detected by hematoxylin-eosin staining. The myeloperoxidase （ MPO） activity of lung tissue were detected by ELISA method. The wet and dry weight ratio （ W/D） of lung tissue was detected. The protein expression of HMGB1 , TLR4 and NF-kB in lung tissue were detected by Western blot. Results Compared with the control group, the MPO, lung injury score and lung tissue W/D increased significantly in the model group （P 〈0. 05）. Compared with the model group, the MPO, lung injury score and lung tissue W/D decreased obviously in the dexmedetomidine group （P 〈0. 05） , but they were still higher than those in the control group. Compared with the control group, the MPO, protein expression of HMGB1, TLR4 and NF-kB increased significantly in the model group （ P 〈 0. 05 ） . Compared with the model group, the protein expression of HMGB1, TLR4 and NF-kB of the dexmedetomidine group significant-ly decreased （P 〈0. 05） , but still higher than those in the control group. Conclusion Dexmedetomidine can inhibit HMGB1/TLR4/NF-kB signaling pathways, reduce inflammation, playing a role of protection for sepsis-induce lung injury.
出处
《临床肺科杂志》
2017年第10期1760-1763,共4页
Journal of Clinical Pulmonary Medicine
基金
湖北省自然科学基金面上项目(No 2014CFC1076)
