28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a 1H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO?+?vehicle; MCAO?+?B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine, O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats.
目的: 观察健康志愿者不同功率递增速率完成症状限制性极限心肺运动试验(CPET)对CPET亚极限运动相关核心指标的影响。方法: 选择12名健康志愿者在一周内不同工作天随机完成中等适度程度(30 W/min)及比较低(10 W/min)和比较高(60 W/min)3种不同功率递增速率CPET。按标准方法比较12名志愿者CPET亚极限运动相关核心指标:无氧阈(AT)、单位功率摄氧量(ΔVO2/ΔWR)、摄氧通气有效性峰值平台(OUEP)、二氧化碳通气当量平均90 s最低值(Lowest VE/ VCO2)、二氧化碳通气当量斜率(VE/ VCO2 Slope)及截距(intercept)和无氧阈时的摄氧通气效率值(VO2/ VE@AT)和无氧阈时的二氧化碳通气当量值(VE/ VCO2@AT)。对三组不同功率递增速率下各个指标的差异组间两两比较。结果: 中等适度功率递增速率组与比较低和比较高功率递增速率组相比摄氧通气有效性峰值平台(42.22±4.76 vs 39.54±3.30 vs 39.29±4.29)和二氧化碳通气当量平均90 s最小值(24.13±2.88 vs 25.60±2.08 vs 26.06±3.05)明显好,差异有统计学意义(P<0.05);比较低、比较高功率递增速率组与中等适度功率递增速率组相比,单位功率摄氧量显著升高和降低((8.45±0.66 vs 10.04±0.58 vs 7.16±0.60)ml/(min·kg)),差异有统计学意义(P<0.05);无氧阈值没有发生明显改变((0.87±0.19 vs 0.87±0.19 vs 0.89±0.19)L/min),差异无统计学意义(P>0.05);结论: 比较低、比较高功率递增速率可以明显改变摄氧通气有效性、二氧化碳排出通气有效性、单位功率摄氧量等CPET亚极限运动相关指标;选择比较低和比较高的功率递增速率和适度功率递增速率CPET相比明显降低了健康个体的摄氧通气有效性和二氧化碳排出通气有效性。CPET规范化操作要求选择适合受试者的功率递增速率,这样得到的CPET亚极限相关指标才最能反应受试者的真实功能状态。 相似文献