白术内酯Ⅰ改善术后肠梗阻大鼠的肠功能、炎症反应、细菌移位及肠道屏障

背景白术内酯Ⅰ(atractylenolideⅠ,AT-1)具有抗炎、抗氧化、抑制肠损伤和改善肠屏障功能的作用,但其对术后肠梗阻(postoperative ileus,POI)的影响和机制并不清楚.目的探讨AT-1对POI大鼠的肠功能、炎症反应、细菌移位及肠道屏障的影响,并探讨初步机制.方法60只泼累格·多雷雄性大鼠,分为5组:对照组、模型组、及低、中、高剂量AT-1干预组,每组12只.用摩擦肠管法构建POI大鼠模型,低、中、高剂量AT-1干预组分别在造模前1 h和造模后1-3 d通过尾静脉注射20、40和80 mg/kg AT-1,每天1次.肠推进实验评估肠推进功能,异硫氰酸酯-葡聚糖法检测肠通透性;苏木精-伊红染色观察小肠组织病理形态;生化分析仪计数外周血白细胞和粒细胞含量,酶联免疫吸附试验法检测血清中白细胞介素(interleukin,IL)-6、IL-1β、肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、内毒素、脂多糖和D-乳酸水平;免疫组化检测肠组织中溶霉菌(Lysozyme)、绒毛蛋白(Villin)、闭锁小带蛋白1(zonula occludens protein 1,ZO-1)和密封蛋白(Claudin)表达分布情况;蛋白质免疫印迹法检测肠组织中核因子κB(nuclear factor kappa-B,NF-κB)相关蛋白表达.结果相比于对照组,模型组小肠绒毛断裂或脱落,隐窝丢失,肠推进功能降低,肠道通透性增加;相比于模型组,AT-1干预组小肠绒毛变长和隐窝增多,肠推进功能增高,肠道通透性降低.免疫组化结果显示,相比于对照组,模型组小肠组织中Lysozyme、Villin、ZO-1和Claudin表达降低,而AT-1干预组上述蛋白表达增高.生化检验结果显示,相比于对照组,模型组外周血中白细胞和中性粒细胞数增多,血清中IL-6、IL-1β、TNF-α、内毒素、脂多糖和D-乳酸水平增高;相比于模型组,AT-1干预组上述血液学指标均降低.蛋白质免疫印迹法检测结果显示,相比于对照组,模型组小肠组织中磷酸化(phospho,p)-P65/P65和磷酸化NF-κB抑制蛋白(phospho-inhibitor of NF-κB,p-IκB)/IκB的表达水平均升高;相比于模型组,AT-1干预组p-P65/P65和p-IκB/IκB的表达水平均降低.且以上结果均具有剂量效应.结论AT-1可有效抑制POI大鼠肠道损伤、炎症反应和NF-κB信号活性,同时维持肠屏障功能的完整性并阻止细菌移位.

Aging precipitation behavior and properties of Al-Zn-Mg-Cu-Zr-Er alloy at different quenching rates

The effect of quenching rate on the aging precipitation behavior and properties of Al-Zn-Mg-Cu-Zr-Er alloy was investigated.The scanning electron microscopy,transmission electron microscopy,and atom probe tomography were used to study the characteristics of clusters and precipitates in the alloy.The quench-inducedηphase and a large number of clusters are formed in the air-cooled alloy with the slowest cooling rate,which contributes to an increment of hardness by 24%(HV 26)compared with that of the water-quenched one.However,the aging hardening response speed and peak-aged hardness of the alloy increase with the increase of quenching rate.Meanwhile,the water-quenched alloy after peak aging also has the highest strength,elongation,and corrosion resistance,which is due to the high driving force and increased number density of aging precipitates,and the narrowed precipitate free zones.