Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
目的探讨微生态制剂联合浙贝黄芩汤对急性淋巴细胞白血病(ALL)大剂量化疗后患者粒细胞集落刺激因子受体(G-CSFR)、粒单系集落形成单位(CFU-GM)、肠道菌群及红系爆式集落形成单位(BFU-E)的影响。方法选取延安大学附属医院2019年6月至2022...目的探讨微生态制剂联合浙贝黄芩汤对急性淋巴细胞白血病(ALL)大剂量化疗后患者粒细胞集落刺激因子受体(G-CSFR)、粒单系集落形成单位(CFU-GM)、肠道菌群及红系爆式集落形成单位(BFU-E)的影响。方法选取延安大学附属医院2019年6月至2022年12月收治的ALL患者130例作为研究对象,根据治疗方法将患者分为A组、B组、C组,3组患者均接受大剂量化疗,化疗结束48 h后A组患者实施常规治疗,B组患者单纯浙贝黄芩汤治疗,C组给予微生态制剂联合浙贝黄芩汤治疗,治疗12 d后,对3组患者G-CSFR、CFU-GM、BFU-E表达情况及血细胞数量进行检测。结果治疗后,C组血红蛋白、白细胞、血小板[(79±6)g/L、(3.8±0.4)×10^(9)/L、(66.4±3.6)×10^(9)/L]与A组[(59±7)g/L、(3.2±0.4)×10^(9)/L、(52.6±2.8)×10^(9)/L]、B组[(61±7)g/L、(3.1±0.3)×10^(9)/L、(52.8±2.6)×10^(9)/L]对比,差异有统计学意义(P<0.05)。C组G-CSFR(5.35±0.16)pg/ml和白细胞介素-11受体(IL-11R)(6.38±0.54)μg/kg水平均高于A组[(2.23±0.13)pg/ml和(1.49±0.24)μg/kg]和B组[(2.31±0.16)pg/ml和(2.31±0.49)μg/kg]差异有统计学意义(P<0.05)。治疗后,C组患者7 d CFU-GM(18.5±6.0)个和14 d BFU-E(83.5±7.5)个高于A组[7 d CFU-GM(9.5±2.0)个和14 d BFU-E(59.5±6.5)个]和B组[7 d CFU-GM(12.0±6.5)个和14 d BFU-E(63.5±5.0)个],差异有统计学意义(P<0.05)。7 d后,C组双歧杆菌(12.56±3.25)lgCFU/g、乳酸杆菌(13.56±2.58)lgCFU/g、肠杆菌(5.12±1.45)lgCFU/g、肠球菌(5.14±0.58)lgCFU/g高于A组[(9.26±1.03)lg CFU/g、(8.65±0.84)lg CFU/g、(8.08±0.64)lgCFU/g、(8.15±0.46)lgCFU/g]和B组[(11.35±1.36)lg CFU/g、(12.43±1.14)lgCFU/g、(6.49±0.55)lgCFU/g、(6.66±0.43)lgCFU/g],差异有统计学意义(P<0.05)。结论微生态制剂联合浙贝黄芩汤治疗可以有效提高ALL大剂量化疗后患者的G-CSFR、CFU-GM、BFU-E水平,可能更好地改善化疗引起的患者骨髓抑制情况,改善肠道菌群,具有临床研究价值。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
文摘目的探讨微生态制剂联合浙贝黄芩汤对急性淋巴细胞白血病(ALL)大剂量化疗后患者粒细胞集落刺激因子受体(G-CSFR)、粒单系集落形成单位(CFU-GM)、肠道菌群及红系爆式集落形成单位(BFU-E)的影响。方法选取延安大学附属医院2019年6月至2022年12月收治的ALL患者130例作为研究对象,根据治疗方法将患者分为A组、B组、C组,3组患者均接受大剂量化疗,化疗结束48 h后A组患者实施常规治疗,B组患者单纯浙贝黄芩汤治疗,C组给予微生态制剂联合浙贝黄芩汤治疗,治疗12 d后,对3组患者G-CSFR、CFU-GM、BFU-E表达情况及血细胞数量进行检测。结果治疗后,C组血红蛋白、白细胞、血小板[(79±6)g/L、(3.8±0.4)×10^(9)/L、(66.4±3.6)×10^(9)/L]与A组[(59±7)g/L、(3.2±0.4)×10^(9)/L、(52.6±2.8)×10^(9)/L]、B组[(61±7)g/L、(3.1±0.3)×10^(9)/L、(52.8±2.6)×10^(9)/L]对比,差异有统计学意义(P<0.05)。C组G-CSFR(5.35±0.16)pg/ml和白细胞介素-11受体(IL-11R)(6.38±0.54)μg/kg水平均高于A组[(2.23±0.13)pg/ml和(1.49±0.24)μg/kg]和B组[(2.31±0.16)pg/ml和(2.31±0.49)μg/kg]差异有统计学意义(P<0.05)。治疗后,C组患者7 d CFU-GM(18.5±6.0)个和14 d BFU-E(83.5±7.5)个高于A组[7 d CFU-GM(9.5±2.0)个和14 d BFU-E(59.5±6.5)个]和B组[7 d CFU-GM(12.0±6.5)个和14 d BFU-E(63.5±5.0)个],差异有统计学意义(P<0.05)。7 d后,C组双歧杆菌(12.56±3.25)lgCFU/g、乳酸杆菌(13.56±2.58)lgCFU/g、肠杆菌(5.12±1.45)lgCFU/g、肠球菌(5.14±0.58)lgCFU/g高于A组[(9.26±1.03)lg CFU/g、(8.65±0.84)lg CFU/g、(8.08±0.64)lgCFU/g、(8.15±0.46)lgCFU/g]和B组[(11.35±1.36)lg CFU/g、(12.43±1.14)lgCFU/g、(6.49±0.55)lgCFU/g、(6.66±0.43)lgCFU/g],差异有统计学意义(P<0.05)。结论微生态制剂联合浙贝黄芩汤治疗可以有效提高ALL大剂量化疗后患者的G-CSFR、CFU-GM、BFU-E水平,可能更好地改善化疗引起的患者骨髓抑制情况,改善肠道菌群,具有临床研究价值。
