目的:探讨川芎嗪对脊髓损伤的修复作用及机理。方法:将90例不同程度的脊髓损伤患者按照随机盲法分成三组,分别为对照组、高剂量川芎嗪组和低剂量川芎嗪组,每组30人。对照组患者在治疗过程中静脉滴注250 m L 0. 9%氯化钠注射液,连续静滴1...目的:探讨川芎嗪对脊髓损伤的修复作用及机理。方法:将90例不同程度的脊髓损伤患者按照随机盲法分成三组,分别为对照组、高剂量川芎嗪组和低剂量川芎嗪组,每组30人。对照组患者在治疗过程中静脉滴注250 m L 0. 9%氯化钠注射液,连续静滴14 d。高剂量川芎嗪组病例静脉滴注250 m L0. 9%氯化钠注射液+240 mg川芎嗪,连续静滴14 d。低剂量川芎嗪组病例静脉滴注250 m L 0. 9%氯化钠注射液+120 mg川芎嗪,连续静滴14 d。每个患者静脉滴注后进行腰椎穿刺抽取脑脊液进行实时定量PCR测定和促炎性细胞因子的生化检测。结果:与对照组相比,应用川芎嗪治疗的脊髓损伤患者脑脊液中TNF-α与IL-1β的mRNA表达降低,与低剂量组相比,高剂量组降低更加明显。另外,应用川芎嗪治疗的脊髓损伤患者脑脊液中Nrf2、GCLc与GCLm的mRNA表达上调,与低剂量组相比,高剂量组患者上调更加明显。结论:川芎嗪可能通过改善炎性反应及应激反应来促进脊髓损伤的康复。展开更多
Homology modeling and structural analysis of human glutamate cysteine ligase catalytic subunit (hGCLC) were performed with a software package the Molecular Operating Environment. A yeast GCLC (yGCLC;PDB code: 3LVV) wa...Homology modeling and structural analysis of human glutamate cysteine ligase catalytic subunit (hGCLC) were performed with a software package the Molecular Operating Environment. A yeast GCLC (yGCLC;PDB code: 3LVV) was selected as a template for the 3D structure modeling of hGCLC. The modeled hGCLC showed significant 3D similarities at the ligand biding site (LBS) to the yGCLC structure. The contact energy profiles of the hGCLC model were in good agreement with those of the yGCLC structure. Ramachandran plots revealed that only 1.4% of the amino acid residues were in the disfavored region for hGCLC. The molecular electrostatic potential (MEP) map of the hGCLC model exhibited that the model was slightly different from the yGCLC model electrostatically at the LBS. Further, docking simulations revealed the similarity of the ligand-receptor bound location between the hGCLC and yGCLC models. The different binding orientations between the glutathione (GSH)-hGCLC and GSH-yGCLC complexes reflected the different MEP maps at the LBSs between the hGCLC and yGCLC models. These results indicate that the hGCLC model was successfully modeled and analyzed. To the best of our knowledge, this is the first report of a hGCLC model with detailed analyses, and our data verify that the model can be utilized for application to target hGCLC for the development of anticancer drugs.展开更多
文摘目的:探讨川芎嗪对脊髓损伤的修复作用及机理。方法:将90例不同程度的脊髓损伤患者按照随机盲法分成三组,分别为对照组、高剂量川芎嗪组和低剂量川芎嗪组,每组30人。对照组患者在治疗过程中静脉滴注250 m L 0. 9%氯化钠注射液,连续静滴14 d。高剂量川芎嗪组病例静脉滴注250 m L0. 9%氯化钠注射液+240 mg川芎嗪,连续静滴14 d。低剂量川芎嗪组病例静脉滴注250 m L 0. 9%氯化钠注射液+120 mg川芎嗪,连续静滴14 d。每个患者静脉滴注后进行腰椎穿刺抽取脑脊液进行实时定量PCR测定和促炎性细胞因子的生化检测。结果:与对照组相比,应用川芎嗪治疗的脊髓损伤患者脑脊液中TNF-α与IL-1β的mRNA表达降低,与低剂量组相比,高剂量组降低更加明显。另外,应用川芎嗪治疗的脊髓损伤患者脑脊液中Nrf2、GCLc与GCLm的mRNA表达上调,与低剂量组相比,高剂量组患者上调更加明显。结论:川芎嗪可能通过改善炎性反应及应激反应来促进脊髓损伤的康复。
文摘Homology modeling and structural analysis of human glutamate cysteine ligase catalytic subunit (hGCLC) were performed with a software package the Molecular Operating Environment. A yeast GCLC (yGCLC;PDB code: 3LVV) was selected as a template for the 3D structure modeling of hGCLC. The modeled hGCLC showed significant 3D similarities at the ligand biding site (LBS) to the yGCLC structure. The contact energy profiles of the hGCLC model were in good agreement with those of the yGCLC structure. Ramachandran plots revealed that only 1.4% of the amino acid residues were in the disfavored region for hGCLC. The molecular electrostatic potential (MEP) map of the hGCLC model exhibited that the model was slightly different from the yGCLC model electrostatically at the LBS. Further, docking simulations revealed the similarity of the ligand-receptor bound location between the hGCLC and yGCLC models. The different binding orientations between the glutathione (GSH)-hGCLC and GSH-yGCLC complexes reflected the different MEP maps at the LBSs between the hGCLC and yGCLC models. These results indicate that the hGCLC model was successfully modeled and analyzed. To the best of our knowledge, this is the first report of a hGCLC model with detailed analyses, and our data verify that the model can be utilized for application to target hGCLC for the development of anticancer drugs.
