目的:研究柚皮素(Nar)对脂多糖(LPS)诱导的脓毒症小鼠肠道粘膜损伤的保护作用。方法:将雄性25~30 g ICR小鼠随机分为对照组(control组,腹腔注射等量的PBS)、脓毒症模型组(LPS组,腹腔注射LPS)和柚皮素治疗组(LPS+Nar组),每组12只,造模后2...目的:研究柚皮素(Nar)对脂多糖(LPS)诱导的脓毒症小鼠肠道粘膜损伤的保护作用。方法:将雄性25~30 g ICR小鼠随机分为对照组(control组,腹腔注射等量的PBS)、脓毒症模型组(LPS组,腹腔注射LPS)和柚皮素治疗组(LPS+Nar组),每组12只,造模后24 h取材进行肠道组织病理检测及评分;免疫荧光法检测细胞凋亡、肠道上皮紧密连接蛋白闭锁小带蛋白-1(ZO-1)和Occludin表达;免疫组织化学方法检测细胞凋亡关键蛋白Caspase3表达。结果:与脓毒症模型组相比,Nar治疗组小鼠肠道病理损伤显著减轻。脓毒症模型组小鼠肠道上皮细胞凋亡显著增加,Nar治疗后肠道上皮细胞凋亡减轻,Caspase3表达下降,差别有统计学意义(P<0.01)。荧光染色检测显示,与对照组相比,脓毒症模型组小鼠肠道Occludin表达显著下降,Nar干预组较脓毒症模型组表达上升(P<0.05);脓毒症模型组小鼠肠道ZO-1表达显著下降,Nar干预组较脓毒症组表达上升(P<0.05)。结论:Nar对LPS诱导的脓毒症小鼠肠道粘膜具有一定的保护作用,有望为保护脓毒症肠粘膜屏障功能提供新的治疗方法。展开更多
目的:研究保护素D1,一种鱼油的代谢产物,对重症急性胰腺炎(SAP)小鼠肠粘膜损伤的保护作用。方法:将雄性25~30 g ICR小鼠随机分为假手术组(Sham组,行开腹关腹假手术操作)、重症胰腺炎模型组(SAP组,开腹胰管结扎建立SAP模型)和保护素D1治...目的:研究保护素D1,一种鱼油的代谢产物,对重症急性胰腺炎(SAP)小鼠肠粘膜损伤的保护作用。方法:将雄性25~30 g ICR小鼠随机分为假手术组(Sham组,行开腹关腹假手术操作)、重症胰腺炎模型组(SAP组,开腹胰管结扎建立SAP模型)和保护素D1治疗组(SAP+protectin D1组,SAP造模1 h后经眼内眦注射保护素D1,2 ng/只),每组12只,造模后24 h取材进行肠道组织病理检测及评分;免疫荧光法检测细胞凋亡、肠道上皮紧密连接蛋白闭锁小带蛋白-1(ZO-1)和Occludin表达;免疫组织化学方法检测细胞凋亡关键蛋白Caspase3表达。结果:与SAP组相比,保护素D1治疗组小鼠肠道病理损伤显著减轻。SAP组小鼠肠道上皮细胞凋亡显著增加,保护素D1治疗后肠道上皮细胞凋亡减轻,Caspase3表达下降,差异有统计学意义(P<0.01)。荧光染色检测显示,与假手术组相比,SAP模型组小鼠肠道Occludin表达显著下降,保护素D1治疗组较SAP模型组表达上升(P<0.01);SAP组小鼠肠道ZO-1表达显著下降,保护素D1治疗组较SAP组表达上升(P<0.05)。结论:保护素D1对SAP模型小鼠肠道粘膜具有保护作用,有望为SAP肠粘膜屏障功能损害提供新的治疗方法。展开更多
In the present study, we investigated the activation of protein kinase C （PKC） family in mouse embryonic fibroblast NIH3T3 cells using gadolinium chloride as a representative lanthanide ion. With live cell imaging s...In the present study, we investigated the activation of protein kinase C （PKC） family in mouse embryonic fibroblast NIH3T3 cells using gadolinium chloride as a representative lanthanide ion. With live cell imaging system and confocal laser scanning microscopy, we found that the treatment of 50 μM GdCI3 promoted cell survival under the condition of serum-starvation. Moreover, better cell attachment and cytoskeleton reorganization were also observed. Additionally, GdC13 treatment resulted in the phosphorylation of PKC family at different time points. Furthermore, bisindolylmaleimide （a PKCpan inhibitor） could efficiently reduce the level of phosphorylated PKCpan （βIISer660）, alleviating ERK activation induced by GdC13. This finding indicated that the PKC activation was involved in GdC13-induced MAPK/ERK signaling and thus might contribute to GdClβ-indueed cell cycle progression and cell survival.展开更多
In the present study, we investigated the transformed species and the absorptive mechanism of rare earth elements（REEs） in gastrointestinal（GI） tract, using La Cl3 and La Cit as representative compounds. Artificia...In the present study, we investigated the transformed species and the absorptive mechanism of rare earth elements（REEs） in gastrointestinal（GI） tract, using La Cl3 and La Cit as representative compounds. Artificial gastric and intestinal fluids were used to simulate the environment of the digestive tract in vivo. The inductively coupled plasma mass spectrometry（ICP-MS） result showed that more than 99.9% of La Cl3 and La Cit formed precipitation in artificial intestinal fluid, with the average size distribution of 200 nm（2-h incubation） increasing to 600 nm（24-h incubation） determined by dynamic light scattering（DLS）, indicating the aggregation of the particles. The Fourier transform infrared spectroscopy（FTIR） analysis demonstrated that the constituents of these particles were mainly in the form of lanthanum phosphates. To explore the transport mechanism of REEs in GI tract, the mice Peyer＇s patches（PPs） and intestinal epithelium were separated to evaluate the content of lanthanum by ICP-MS following oral administration with 2 or 100 mg/kg/day of La Cit for 7 d. The results showed that the amount of lanthanum phosphate particles absorbed by PPs was significantly greater than that of intestinal epithelium, indicating that lanthanum particles might be phagocytosed mainly by M cells located in the follicle-associated epithelium（FAE） overlying PPs. Furthermore, Caco-2 cell monoculture and Caco-2/Raji B cell coculture models were established to simulate intestinal epithelial cells and FAE, respectively. The result showed that the transport of lanthanum in Caco-2/Raji B coculture model was significantly higher than that in Caco-2 monoculture model（about 60 times higher）, and the level of lanthanum in the basal compartment of Caco-2 monoculture model was very low, supporting that M cells were the main route for lanthanum phosphate particles to be transported and absorbed. Taken together, these data suggested that La Cl3 and La Cit in GI tract were absorbed mainly via M cells with lanthanum phosphates as transformed species. The obtained results would provide the theoretical basis for the rational application of REEs in agriculture and medicine.展开更多
文摘目的:研究柚皮素(Nar)对脂多糖(LPS)诱导的脓毒症小鼠肠道粘膜损伤的保护作用。方法:将雄性25~30 g ICR小鼠随机分为对照组(control组,腹腔注射等量的PBS)、脓毒症模型组(LPS组,腹腔注射LPS)和柚皮素治疗组(LPS+Nar组),每组12只,造模后24 h取材进行肠道组织病理检测及评分;免疫荧光法检测细胞凋亡、肠道上皮紧密连接蛋白闭锁小带蛋白-1(ZO-1)和Occludin表达;免疫组织化学方法检测细胞凋亡关键蛋白Caspase3表达。结果:与脓毒症模型组相比,Nar治疗组小鼠肠道病理损伤显著减轻。脓毒症模型组小鼠肠道上皮细胞凋亡显著增加,Nar治疗后肠道上皮细胞凋亡减轻,Caspase3表达下降,差别有统计学意义(P<0.01)。荧光染色检测显示,与对照组相比,脓毒症模型组小鼠肠道Occludin表达显著下降,Nar干预组较脓毒症模型组表达上升(P<0.05);脓毒症模型组小鼠肠道ZO-1表达显著下降,Nar干预组较脓毒症组表达上升(P<0.05)。结论:Nar对LPS诱导的脓毒症小鼠肠道粘膜具有一定的保护作用,有望为保护脓毒症肠粘膜屏障功能提供新的治疗方法。
基金National Natural Science Foundation of China (Grant No.21277006 and 20637010)
文摘In the present study, we investigated the activation of protein kinase C （PKC） family in mouse embryonic fibroblast NIH3T3 cells using gadolinium chloride as a representative lanthanide ion. With live cell imaging system and confocal laser scanning microscopy, we found that the treatment of 50 μM GdCI3 promoted cell survival under the condition of serum-starvation. Moreover, better cell attachment and cytoskeleton reorganization were also observed. Additionally, GdC13 treatment resulted in the phosphorylation of PKC family at different time points. Furthermore, bisindolylmaleimide （a PKCpan inhibitor） could efficiently reduce the level of phosphorylated PKCpan （βIISer660）, alleviating ERK activation induced by GdC13. This finding indicated that the PKC activation was involved in GdC13-induced MAPK/ERK signaling and thus might contribute to GdClβ-indueed cell cycle progression and cell survival.
基金National Natural Science Foundation of China(Grant No.21277006 and 21671009)
文摘In the present study, we investigated the transformed species and the absorptive mechanism of rare earth elements（REEs） in gastrointestinal（GI） tract, using La Cl3 and La Cit as representative compounds. Artificial gastric and intestinal fluids were used to simulate the environment of the digestive tract in vivo. The inductively coupled plasma mass spectrometry（ICP-MS） result showed that more than 99.9% of La Cl3 and La Cit formed precipitation in artificial intestinal fluid, with the average size distribution of 200 nm（2-h incubation） increasing to 600 nm（24-h incubation） determined by dynamic light scattering（DLS）, indicating the aggregation of the particles. The Fourier transform infrared spectroscopy（FTIR） analysis demonstrated that the constituents of these particles were mainly in the form of lanthanum phosphates. To explore the transport mechanism of REEs in GI tract, the mice Peyer＇s patches（PPs） and intestinal epithelium were separated to evaluate the content of lanthanum by ICP-MS following oral administration with 2 or 100 mg/kg/day of La Cit for 7 d. The results showed that the amount of lanthanum phosphate particles absorbed by PPs was significantly greater than that of intestinal epithelium, indicating that lanthanum particles might be phagocytosed mainly by M cells located in the follicle-associated epithelium（FAE） overlying PPs. Furthermore, Caco-2 cell monoculture and Caco-2/Raji B cell coculture models were established to simulate intestinal epithelial cells and FAE, respectively. The result showed that the transport of lanthanum in Caco-2/Raji B coculture model was significantly higher than that in Caco-2 monoculture model（about 60 times higher）, and the level of lanthanum in the basal compartment of Caco-2 monoculture model was very low, supporting that M cells were the main route for lanthanum phosphate particles to be transported and absorbed. Taken together, these data suggested that La Cl3 and La Cit in GI tract were absorbed mainly via M cells with lanthanum phosphates as transformed species. The obtained results would provide the theoretical basis for the rational application of REEs in agriculture and medicine.
