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@#Abstract: Integrated stress response is an adaptive response produced by eukaryotic cells after intracellular and extracellular stimulation. The activation of integrated stress response inhibits the translation of most proteins, yet it can promote the translation of certain proteins to cope with complex cellular microenvironment changes. A large number of studies have found that in a variety of nervous system diseases, the integrated stress response can be activated by stress signals of disease-related cells and participates in the occurrence and progression of diseases through processes such as learning and memory consolidation, myelin regeneration and synaptic plasticity. This article summarizes the role, mechanism and possible drug targets of integrated stress response in central nervous system diseases and discusses the potential of pharmacological methods to regulate integrated stress response in the treatment of central nervous system diseases, in order to provide reference for pathological research on and drug development for central nervous system diseases.
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@#As a key component of glutamatergic system, metabotropic glutamate receptor 5 (mGluR5) has been extensively involved in the regulation of physiological processes such as synaptic transmission, synaptic plasticity and synaptic excitation/inhibition balance.Over the past few decades, mGluR5 has been found to be closely related to multiple neurological and psychiatric disorders, thus it is of considerable interest as a drug target in the treatment of such disorders.This review summarizes the structure and distribution of mGluR5, its normal physiological function, its pathological roles in related central nervous system (CNS) diseases, as well as the current status of its drug development, in order to provide reference for further investigation.
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Objective:To observe the effects of Yikunjing capsules on the bone histomorphometry indexes and the serum Interleukin-6 (IL-6) level in mice with osteoporosis.Methods:60 cases ofC57 female mice were randomly divided into 5 groups,such as model group (equal volume of normal saline),estrogen group (nilestriol,0.25 mg/kg),Yikunjing capsules high dose group (1.44 g/kg),Yikunjing capsules medium dose group (0.72 g/kg) and Yikunjing capsules low dose group (0.36 g/kg),sham group (equal volume of normal saline) were treated with sham operation.The mice in each group was intragastrically administrated for 70 days.Enzyme linked immunosorbent assay (ELISA) was used to detect the serum IL-6 level.The bone histomorphometry index were detected with BI-2000 Medical Image Analysis System.And the Number of blood vessels in distal femoral metaphysis of each group was measured by CT.Results:Compared with the sham group,the width and area of trabecular bone,the thickness of cortical bone,area of trabecular bone,the number of osteoblasts,the bone mineral density and the number of blood vessels in model group were significantly reduced(P＜0.05),while the number of osteoclasts and serum IL-6 level were significantly increased (P＜0.05).Compared with the model group,above indexes in estrogen group,Yikunjing capsules high,medium,low dose group were improved (P＜0.05),and the effect of Yikunjing capsules high dose group and estrogen group was almost the same (P＞0.05).Conclusion:Yikunjing capsules can rectify the bone histomorphometry indexes reduce the serum IL-6 level and increase the number of blood vessels in mice with osteoporosis,and intragastrically administrating 1.44 g/kg Yikunjing capsules could get the better effect.
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Objective To investigate the pharmacokinetics of intravenously infused domestic alfentanil in the patients undergoing general anesthesia.Methods Twelve American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 18-47 yr,weighing 49-86 kg,scheduled for elective subtotal thyroidectomy under general anesthesia,were enrolled in the study.Anesthesia was induced with iv midazolam 0.02 mg/kg,alfentanil 25 μg/kg,propofol 1.5 mg/kg and rocuronium 0.8 mg/kg.The patients were endotracheally intubated and mechanically ventilated.Anesthesia was maintained with inhalation of 0.8％-2.0％ sevoflurane,iv infusion of alfentanil 1 μg · kg-1 · min-1,and intermittent iv boluses of rocuronium 10-20 mg,bispectral index value was maintained at 40-60,and infusion was stopped at 10 min before the end of surgery.Before induction of anesthesia,at 1,3,5,8,10,14,20,35,65,95 and 125 min ofalfentanil infusion,and at 5,15,30,60,120,180,240,300 and 360 min after termination of alfentanil infusion,venous blood samples were collected for determination of the plasma concentration of alfentanil (by high performance liquid chromatography-mass spectrometry/mass spectrometry).DAS 3.0 software was used to analyze the pharmacokinetic parameters of alfentanil.Results The pharmacokinetics of domestic alfentanil was best described by a two-compartment pharmacokinetic model.The distribution half-life was (1.8 ± 0.8) min,and the elimination half-life was (91±22) min.The volume of distribution at steady state was (0.38±0.12) L/kg,and the clearance was (4.3± 1.6) ml · kg-1 · min-1.The elimination of domestic alfentanil followed the first-order kinetics.Conclusion The distribution of intravenously infused domestic alfentanil is fitted to a two-compartment pharmacokinetic model with elimination following the first-order kinetics in the patients undergoing general anesthesia.
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Objective To develop a forebrain ischemic preconditioning model in C57BL/6 mice and determine the protective effects of ischemic preconditioning on brain ischemia-reperfusion injury. Methods Forty-eight 8-10 week old C57BL/6 mice weighing 19-23 g were randomly divided into four groups of 12 animals, A: sham-operation group; B: ischemic preconditioning group; C: ischemia-reperfusion group (I/ R); D: ischemic preconditioning + I/R group. The animals were anesthetized with halothane. Bilateral common carotid artery (BCCA) was exposed and occluded for 6min (ischemic preconditioning) or 18min followed by 3h reperfusion (I/R). In group D BCCA was firstly occluded for 6 min, then released and 48h later occluded again for 18min followed by 3h reperfusion. 6 animals in each group were sacrificed 72h after reperfusion and brain was immediately removed for detection of DNA fragmentation of neurons in hippocampus by TUNEL. Another 6 animals were sacrificed on the 7th day after I/R and neuronal damage was identified by microtubule-associated protein-2 immunochemistry and quantified by cresyl violet staining. Results I/R resulted in severe damage to hippocampus in C57BL/6 mice. The ischemic preconditioning caused neither noticeable hippocampal neuronal damage nor DNA fragmentation but significantly reduced hippocampal neuronal damage and DNA fragmentation caused by I/R. Conclusion Our results indicate that hippocampal neuronal injury induced by I/R can be greatly reduced by ischemic preconditioning in C57BL/6 mice. Many kinds of gene-altered C57BL/6 mice are available, this preconditioning model may provide an useful method for investigating the molecular mechanisms of ischemic preconditioning.