摘要
目的 探讨吴茱萸碱(EVO)调节高迁移率族蛋白1/晚期糖基化终末产物受体(HMGB1/RAGE)信号通路对脓毒症大鼠急性肺损伤(ALI)的影响。方法 SD大鼠随机分为对照组、模型组、EVO组(40 mg/kg EVO)、EVO+HMGB1组(40 mg/kg EVO+500μg HMGB1重组蛋白),每组均12只。除对照组外,其余组采用盲肠结扎穿刺(CLP)法建立脓毒性ALI模型;ELISA法检测血清中炎性因子;苏木精-伊红(HE)染色观察肺组织病理形态;TUNEL染色观察肺组织细胞凋亡情况;肺通透性指数(LPI)评估大鼠肺毛细血管渗漏;Western blot检测肺组织Occludin、ZO-1以及HMGB1-RAGE通路相关蛋白表达。结果 对照组肺组织结构正常;与对照组相比,模型组肺组织炎性细胞浸润严重,肺泡壁增厚,弥漫性水肿明显,肺泡间隙变窄,间质充血增强,病理损伤严重,Smith评分(3.10±0.38)、TNF-α、IL-1β、MCP-1含量、细胞凋亡率、LPI水平(2.98±0.12)、HMGB1、RAGE蛋白水平显著升高(P<0.05),Occludin、ZO-1蛋白水平显著下调(P<0.05);与模型组相比,EVO组肺肿胀、充血、炎性细胞浸润现象改善,Smith评分(0.42±0.04)、TNF-α、IL-1β、MCP-1含量、细胞凋亡率、LPI水平(0.97±1.05)、HMGB1、RAGE蛋白水平显著降低(P<0.05),Occludin、ZO-1蛋白水平显著升高(P<0.05);HMGB1过表达消除了EVO对脓毒症大鼠ALI的有利影响。结论 EVO可能通过下调HMGB1-RAGE信号通路对脓毒症大鼠ALI起到改善效果。
Objective To investigate the impacts of Evodiamine(EVO)on acute lung injury(ALI)in septic rats by regulating high⁃mobility group protein 1(HMGB1)/receptor for advanced glycation end products(RAGE)signaling pathway.Methods SD rats were randomly grouped into a control group,a model group,an EVO group(40 mg/kg EVO),and an EVO+HMGB1 group(40 mg/kg EVO+500μg HMGB1 recombinant protein),with 12 in each group.Except for the control group,the other groups used the cecal ligation puncture(CLP)method to establish a septic ALI model;ELISA method was applied to detect inflammatory factors in serum;HE staining was applied to observe the pathological morphology of lung tissue;TUNEL staining was applied to observe the apoptosis of lung tissue cells;the lung permeability index(LPI)was applied to evaluate pulmonary capillary leakage in rats;Western blot was applied to detect the expression of Occludin,ZO⁃1,and HMGB1⁃RAGE pathway related proteins in lung tissue.Results The lung tissue structure of the control group was normal;compared with the control group,the inflammatory cell infiltration in lung tissue in model group was severe,with thickening of alveolar walls,obvious diffuse edema,narrowing of alveolar spaces,enhanced interstitial congestion,and severe pathological damage,the Smith score(3.10±0.38),TNF⁃α,IL⁃1β,MCP⁃1 contents,apoptosis rate,LPI level(2.98±0.12),HMGB1,and RAGE protein levels were obviously increased(P<0.05),the Occludin and ZO⁃1 protein levels were obviously down⁃regulated(P<0.05);compared with the model group,the lung swelling,congestion,and inflammatory cell infiltration in the EVO group improved,the Smith score(0.42±0.04),TNF⁃α,IL⁃1β,MCP⁃1 contents,apoptosis rate,LPI level(0.97±1.05),HMGB1,and RAGE protein levels were obviously reduced(P<0.05),the Occludin and ZO⁃1 protein levels were obviously increased(P<0.05);Overexpression of HMGB1 eliminated the beneficial effect of EVO on ALI in septic rats.Conclusion EVO may improve ALI in septic rats by down⁃regulating the HMGB1⁃RAGE signaling pathway.
作者
潘之得
沙媛媛
郭健
钱义明
胡冠宇
费露颖
PAN Zhi-de;SHA Yuan-yuan;GUO Jian;QIAN Yi-ming;HU Guan-yu;FEI Lu-ying(Department of Emergency,Yueyang Hospital of Integrated Traditonal Chinese and Western Medicine,Shanghai 200437,China)
出处
《解剖学研究》
CAS
2023年第6期541-546,共6页
Anatomy Research
基金
上海市“科技创新行动计划”自然科学基金项目(23ZR1464200)。