Astrocytes are the most important glial cell type in the central nervous system (CNS), which play an important role in maintaining homeostasis, regulating synaptic plasticity and protecting neurons. During pathological damage, astrocytes can differentiate into A1 and A2 subtypes, which play a dual role in blocking or repairing nerve damage and participate in the pathological changes of a variety of CNS diseases such as stroke, Alzheimer's disease, Parkinson's disease, spinal cord injury and cervical spondylotic myelopathy. This review focuses on the phenotype characteristics and activation mechanisms of A1 and A2 astrocytes and their relationships with different CNS diseases, in order to provide reference for treatment of CNS diseases.

AIM:This study aims to investigate the role of dynamin-related protein 1(Drp1)in the A1 type activation of astrocytes and elucidate the underlying mechanism of abnormal astrocyte activation.METHODS:Rat astro-cyte line CTX-TNA2 was divided into control group,astrocyte-conditioned medium(ACM)group,and 5,10 and 25 μmol/L mitochondrial division inhibitor-1(Mdivi-1;a selective inhibitor of Drp1)+ACM group.The cells in ACM group were exposed to ACM containing interleukin-1α(IL-1α),tumor necrosis factor-α(TNF-α)and complement 1q(C1q)for 24 h to induce type A1 activation,while those in Mdivi-1+ACM group were pre-treated with various concentrations of Mdi-vi-1 for 2 h before stimulation with ACM for 24 h.RT-qPCR was used to detect the expression levels of A1 type activation-related indicators IL-1β,TNF-α and IL-10 mRNA in each group.Immunofluorescence was utilized to assess the expres-sion levels of A1 type activation marker molecules C3,inducible nitric oxide synthase(iNOS)and S100 calcium binding protein A10(S100A10).The level of mitochondrial reactive oxygen species(ROS)was measured using MitoSOX Red staining and flow cytometry analysis.The mitochondrial morphology was observed using the MICA full-field imaging analy-sis platform.Lastly,the expression level of mitochondrial fission protein 1(FIS1)and the activation level of Drp1 in each group were evaluated through immunoblotting analysis.RESULTS:The RT-qPCR and immunofluorescence results indi-cated that the ACM group exhibited significantly elevated levels of IL-1β and TNF-α mRNA,and C3 protein expression compared with control group,along with increased iNOS protein expression and reduced IL-10 mRNA and S100A10 pro-tein expression(P＜0.05).Interventions with 10 and 25 μmol/L Mdivi-1 effectively inhibited the rise in IL-1β and TNF-α mRNA,and C3 and iNOS protein expression induced by ACM,while promoting S100A10 expression.MitoSOX Red staining revealed a significant increase in mitochondrial ROS levels in astrocytes stimulated by ACM,which was effectively re-versed by Mdivi-1 intervention.The MICA full-field imaging analysis platform demonstrated that ACM induced the forma-tion of round-shaped mitochondria in astrocytes,while 10 and 25 μmol/L Mdivi-1 interventions facilitated the restoration of their tubular shape.Additionally,Western blot results confirmed that Mdivi-1 intervention effectively reversed the acti-vation of Drp1 and FIS1.CONCLUSION:The Drp1-mediated mitochondrial fission represents one of the intrinsic molecu-lar mechanisms underlying A1 type activation of astrocytes,and Mdivi-1,as a selective inhibitor of Drp1,can effectively inhibit abnormal astrocyte activation.

AIM:This study aims to investigate the role of dynamin-related protein 1(Drp1)in the A1 type activation of astrocytes and elucidate the underlying mechanism of abnormal astrocyte activation.METHODS:Rat astro-cyte line CTX-TNA2 was divided into control group,astrocyte-conditioned medium(ACM)group,and 5,10 and 25 μmol/L mitochondrial division inhibitor-1(Mdivi-1;a selective inhibitor of Drp1)+ACM group.The cells in ACM group were exposed to ACM containing interleukin-1α(IL-1α),tumor necrosis factor-α(TNF-α)and complement 1q(C1q)for 24 h to induce type A1 activation,while those in Mdivi-1+ACM group were pre-treated with various concentrations of Mdi-vi-1 for 2 h before stimulation with ACM for 24 h.RT-qPCR was used to detect the expression levels of A1 type activation-related indicators IL-1β,TNF-α and IL-10 mRNA in each group.Immunofluorescence was utilized to assess the expres-sion levels of A1 type activation marker molecules C3,inducible nitric oxide synthase(iNOS)and S100 calcium binding protein A10(S100A10).The level of mitochondrial reactive oxygen species(ROS)was measured using MitoSOX Red staining and flow cytometry analysis.The mitochondrial morphology was observed using the MICA full-field imaging analy-sis platform.Lastly,the expression level of mitochondrial fission protein 1(FIS1)and the activation level of Drp1 in each group were evaluated through immunoblotting analysis.RESULTS:The RT-qPCR and immunofluorescence results indi-cated that the ACM group exhibited significantly elevated levels of IL-1β and TNF-α mRNA,and C3 protein expression compared with control group,along with increased iNOS protein expression and reduced IL-10 mRNA and S100A10 pro-tein expression(P＜0.05).Interventions with 10 and 25 μmol/L Mdivi-1 effectively inhibited the rise in IL-1β and TNF-α mRNA,and C3 and iNOS protein expression induced by ACM,while promoting S100A10 expression.MitoSOX Red staining revealed a significant increase in mitochondrial ROS levels in astrocytes stimulated by ACM,which was effectively re-versed by Mdivi-1 intervention.The MICA full-field imaging analysis platform demonstrated that ACM induced the forma-tion of round-shaped mitochondria in astrocytes,while 10 and 25 μmol/L Mdivi-1 interventions facilitated the restoration of their tubular shape.Additionally,Western blot results confirmed that Mdivi-1 intervention effectively reversed the acti-vation of Drp1 and FIS1.CONCLUSION:The Drp1-mediated mitochondrial fission represents one of the intrinsic molecu-lar mechanisms underlying A1 type activation of astrocytes,and Mdivi-1,as a selective inhibitor of Drp1,can effectively inhibit abnormal astrocyte activation.

Astrocytes are the most important glial cell type in the central nervous system (CNS), which play an important role in maintaining homeostasis, regulating synaptic plasticity and protecting neurons. During pathological damage, astrocytes can differentiate into A1 and A2 subtypes, which play a dual role in blocking or repairing nerve damage and participate in the pathological changes of a variety of CNS diseases such as stroke, Alzheimer's disease, Parkinson's disease, spinal cord injury and cervical spondylotic myelopathy. This review focuses on the phenotype characteristics and activation mechanisms of A1 and A2 astrocytes and their relationships with different CNS diseases, in order to provide reference for treatment of CNS diseases.

Objective To investigate the effect of dihydroartemisinin(DHA)for enhancing the inhibitory effect of cisplatin(DDP)on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism.Methods CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA(0,5,10,20,40,80,and 160 μmol/L)and DDP(0,4,8,16,32,64,128 μmol/L)for 24 or 48 h,and the combination index of DHA and DDP was calculated using Compusyn software.HNE1/DDP cells treated with DHA,DDP,or their combination for 24 h were examined for cell viability,proliferation and colony formation ability using CCK-8,EdU and colony-forming assays.Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species(ROS).The expression levels of apoptosis-related proteins cleaved PARP,cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting.The effects of N-acetyl-cysteine(a ROS inhibitor)on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed.Results Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells.The combination index of DHA(5 μmol/L)combined with DDP(8,16,32,64,128 μmol/L)were all below 1.Compared with DHA or DDP alone,their combined treatment more potently decreased the cell viability,colony-forming ability and the number of EdU-positive cells,and significantly increased the apoptotic rate,intracellular ROS level,and the expression levels of cleaved PARP,cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells.N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells(P<0.01).Conclusion DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.

Objective To investigate the effect of dihydroartemisinin(DHA)for enhancing the inhibitory effect of cisplatin(DDP)on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism.Methods CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA(0,5,10,20,40,80,and 160 μmol/L)and DDP(0,4,8,16,32,64,128 μmol/L)for 24 or 48 h,and the combination index of DHA and DDP was calculated using Compusyn software.HNE1/DDP cells treated with DHA,DDP,or their combination for 24 h were examined for cell viability,proliferation and colony formation ability using CCK-8,EdU and colony-forming assays.Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species(ROS).The expression levels of apoptosis-related proteins cleaved PARP,cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting.The effects of N-acetyl-cysteine(a ROS inhibitor)on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed.Results Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells.The combination index of DHA(5 μmol/L)combined with DDP(8,16,32,64,128 μmol/L)were all below 1.Compared with DHA or DDP alone,their combined treatment more potently decreased the cell viability,colony-forming ability and the number of EdU-positive cells,and significantly increased the apoptotic rate,intracellular ROS level,and the expression levels of cleaved PARP,cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells.N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells(P<0.01).Conclusion DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.

OBJECTIVE：To preliminarily s tudy the potential mechanism of astragaloside Ⅳ on allergic rhinitis （AR）model mice. METHODS ：C57/BL6 mice were randomly divided into blank group ，model group and astragaloside Ⅳ group，with 10 mice in each group. Except for blank group ，AR model was prepared by sensitization and challenge with ovalbumin on day 0，7，14 and 21-27. Astragaloside Ⅳ group was given astragaloside Ⅳ 40 mg/kg intraperitoneally at the dose of 0.02 mL/g on the 15th to 27th day of modeling （given the drug 1 h before challenge sensitization on the 21st to 27th day ）. Blank group and model group were given constant volume of normal saline intraperitoneally ，once a day. Twenty-four hours after sensitization from the last challenge ， the infiltration of inflammatory cells in the nasal mucosa of each group was observed ，and the contents of interleukin 4（IL-4）， IL-5 and interferon gamma （IFN-γ）in the nasal lavage fluid were measured. The levels of reactive oxygen species （ROS），and the count of phosphorylated Janus kinase 2（p-JAK2）and phosphorylation signal transduction and activation of transcription protein 6 （p-STAT6）positive cells in the nasal mucosa and spleen as well as the phosphorylation levels of JAK 2 and STAT 6 proteins in spleen tissue （i.e. p-JAK 2/JAK2 ratio，p-STAT6/STAT6 ratio）were also determined. RESULTS ：Compared with blank group ，the number of inflammatory cells in the nasal mucosa （eosinophils and mast cells ）in the model group ，the contents of IL- 4 and IL- 5 in the nasal lavage fluid ，and the levels of ROS in the nasal mucosa and spleen tissues in the model group ，the count of p-JAK 2 and p-STAT 6 positive cells increased significantly ，the p-JAK2/JAK2 ratio，p-STAT6/STAT6 ratio in the spleen tissue were significantly increased （P＜0.05），and the content of INF-γ in the nasal lavage fluid was significantly decreased（P＜0.05）. Compared with model group ，the count of inflammatory cells infiltrated in the nasal mucosa ，the contents of IL- 4 and IL- 5 in the nasal cavity lavage fluid ，the level of ROS and the number of p-JAK 2 and p-STAT 6 positive cellsin the nasal mucosa and spleen tissue as well as the p-JAK2/JAK2 ratio and p-STAT 6/STAT6 ratio in spleen tissue were decreased significantly （P＜0.05），and the content of INF-γ in nasal lavage fluid was significantly increased（P＜0.05）. CO NCLUSIONS：Astragaloside Ⅳ can effectively improve the inflammatory response in AR model mice ，the mechanism of which may be related to down-regulation of JAK2/STAT6 signaling pathway and ROS level.

Recently, salvia miltiorrhiza has made a great progress in research of central nervous system (CNS) injury and neurodegeneration. Salvia miltiorrhiza and its active ingredients can exert multiple effects involving reduction of cell loss, attenuation of oxidative stress, improvement of micro-circulation and promotion of neuroregeneration, and show a protective effect on CNS diseases. Regulation of oxidative stress and removing accumulated metabolite may be the important mechanisms by which salvia miltiorrhiza exerts neuroprotective effects. This study will systematically discuss the pharmacological effects and possible mechanisms of salvia miltiorrhiza based on the core pathological changes in CSN diseases, and evaluate its drug safety through combing the related toxicology researches to provide a reference for clinical transformation of Chinese medicine in threatment of CNS diseases.

Objective To investigate the effect of Chinese herbal compound"Jisuikang"on the phagocyto-sis of neuronal debris by microglial cells. Methods To prepare serum containing drugs of JSK and divide them into the low,middle and high dose groups,the blank serum group and LPS+blank serum group. BV2 was labeled by lentiviral vectors containing the green fluorescent protein gene (GFP). To establish the damage neuron model and mix injured neurons with the transfected microglia. To observe the situation of microglia which was affected by serum containing drugs devour the neuronal debris. Results The middle and high dose of JSK showed greater phagocytic percentage and phagocytic index than those of the control group(P<0.001). In comparison of LPS+blank serum group,no significant difference was found in the middle and high dose of JSK. However,to the phagocytic index, which was better than that of LPS+blank serum group(P<0.05). Conclusion JSK may enhance the engulfment of neuron debris by BV2,which could provide a better living environment for the growth of neurons.

Objective: To observe the effect of Yiqi Wenyang Decoction on the infiltration and activation of NK cells in nasal mucosa of mouse model with allergic rhinitis (AR), and to explore the potential mechanism for effective intervention of AR with Yiqi Wenyang Decoction. Methods: Fourty-eight mice were randomly divided into blank group, model group, low, medium and high dose of Yiqi Wenyang Decoction group and Cetirizine group, with 8 rats in each group. After modeling of AR, the model group was filled with 0.9% sodium chloride solution. Yiqi Wenyang Decoction groups of each dose were given different concentrations of Yiqi Wenyang Decoction water extract, while the Cetirizine group was given aqueous solution of Cetirizine. The behavior, morphological changes of nasal mucosa and infiltration of NK cells in nasal mucosa were observed. The levels of IL-4 and INF-γ in nasal lavage fluid were measured. Besides, the drug safety was observed by acute toxicity test. Results: In the respect of behavioral scoring, middle and high dose of Yiqi Wenyang Decoction group were superior to the model group (number of sneezing: q value was 7.189, 8.748, respectively; number of scratching nose: q value was 12.074, 14.560, respectively; all P<0.05). In middle and high dose of Yiqi Wenyang Decoction group, the infiltration of NK cells and nasal lavage fluid IL-4 levels were lower than those in model group (IOD: q value was 10.073, 12.322, respectively; IOD/Area: q value was 10.954, 14.073, respectively; IL-4: q value was 4.705, 6.801, respectively; all P<0.05). There was no significant difference in nasal lavage fluid of INF-γ among each group (Fv=1.166, P>0.05). In acute toxicity test, no obvious poisoning symptoms and death occurred in mice. Conclusion Yiqi Wenyang Decoction can control the nasal symptom, reduce the local NK cell infiltration of nasal mucosa and inhibit the expression of the 2-type cytokines released by NK cells, which may be related with the potential mechanism of effective intervention of AR with Yiqi Wenyang Decoction.