Research progress of neuronal injury mediated by microglial activation and depression / 中国药理学通报

Depression is a common neurological disorder with high incidence, high recurrence and high disability, but its pathogenesis is unclear. In recent years, the protective and attacking effects of glial cells on neurons have become the frontier of neurological disease research. Neuronal injury caused by abnormal activation of microglia (MG) plays an important role in the pathogenesis of depression. In this paper, through literature retrieval by GeenMedical and CNKI, the relevant pathways and key targets of MG activation in depression are summarized so as to provide a theoretical basis for further clinical research.

Cornel iridoid glycoside alleviates microglia-mediated inflammatory response via NLRP3/calpain pathway / 中国药理学与毒理学杂志

OBJECTIVE Vascular dementia(VaD)is associated with cerebral hypoperfusion,which results in long-term cognitive impairment and memory loss.Neuroin-flammation is an important mechanism of vascular demen-tia.Cornel iridoid glycoside(CIG)is the major active con-stituent isolated from the ripe fruit of Cornus officinalis.Previous studies have shown that CIG enhances neuro-logical function in VaD rats.In the present research,we attempted to clarify the molecular processes underlying the role of CIG on neuroinflammation in VaD.METHODS In vivo,we created a chronic cerebral ischemia rat model by ligation of the bilateral common carotid arteries(2VO).The rats were divided into sham operation,2VO,2VO + CIG(60 and120 mg·kg-1·d-1),and 2VO+ butylphthalide(100 mg·kg-1·d-1)groups and then treated rats with differ-ent concentrations of CIG.In vitro,BV2 microglia cells were induced with bacterial lipopolysaccharide(LPS)and interferon-γ(IFN-γ)to construct the model of microglias with analog neuroinflammation.Histopathology and biel-schowsky silver staining were used to detect myelin integrity and neuronal loss.Immunofluorescence was used to observe changes in microglia.Magnetic Luminex Assay was used to detect changes in inflammatory fac-tors.Western blotting,ELISA or calpain activity assay was used to measure the expression and activity of cal-pain,as well as the expression of NLRP3 inflammasome protein.Furthermore,NLRP3 overexpressing cells were used to further elucidate the potential anti-inflammatory molecular mechanism of CIG.RESULTS ① CIG improved neuronal impairment in the brain of 2VO rats.②CIG increased white matter(WM)integrity in 2VO rats.③ CIG reduced microglia inflammatory response in the cortex and hippocampus of 2VO rats.④ CIG inhibited calpain activity in the cortex and hippocampus of 2VO rats.⑤ CIG exerted anti-inflammatory effects on BV2 cells stimulated by LPS and IFN-γ.⑥ CIG Inhibited the expression and activity of calpain in LPS/IFN-γ-activated BV2 cells.⑦ The main component of CIG had a weak binding force to calpain1.⑧ CIG inhibited the activation of the NLRP3 inflammasome.⑨CIG reduced the activity of calpain induced by NLRP3 overexpression.CONCLU-SION CIG inhibits microglial polarization into a proinflam-matory state by attenuating the assembly of the NLRP3 inflammasome and calpain activation,thus reducing brain inflammation,WM injury,and the loss of neurons.To sum up,the present study suggests that CIG inhibits neuroinflammation.The NLRP3/calpain pathway may be the main pathway by which CIG protects against neuroin-flammation.

Effect of hirudin on pulmonary fibrosis by regulating p38MAPK/NF-kB signaling pathway and its mechanism / 中国药理学通报

Aim To observe the effect of hirudin on pulmonary inflammation and fibrosis in rats with bleo-myc in-induced pulmonary fibrosis and the underlying mechanism.Methods Sixty male SD rats were ran¬domly divided into control group, model group, hirudin treatment group ( low,medium and high concentration) and prednisone group.The control group received en-dotracheal injection of saline, while the remaining five groups carried out endotracheal one-time injection of blemycin to establish rat pulmonary fibrosis model.From the second day after modeling, hirudin treatment groups were respectively administered different concen¬trations of hirudin subcutaneous injection, while control group was given saline, and prednisone was gavaged with 5 mg • kg~1 prednisone acetate, then all rats were sacrificed on day 28.Lung lesions were observed by HE and Masson staining.The relative expression levels of COL 1 and ot-SMA mRNA were detected by real¬time fluorescence quantitative PCR.The content of hydroxy proline ( HYP) in lung tissues was determined by kit.The expression levels of p38MAPK/NF-KB sig¬naling pathway related proteins in lung tissues were de¬tected by Western blot, and IL-6 and TNF-cx levels were detected by ELISA.Results Compared with model group, the inflammatory response and interstitial fibrosis of lung tissues were improved, the content of hvdroxvproline decreased, the expression of p-p38 MAPK,NF-kB p-p65and p~IkB protein decreased, and the concentration of TNF-cx and IL-6 decreased after hirudin intervention.Conclusions Hirudin can effec¬tively inhibit alveolar inflammation and reduce the de¬velopment of pulmonary fibrosis, which may be related to regulating p38 MAPK/NF-kB signaling pathway,re¬ducing the inflammatory response of lung tissues and reducing the deposition of extracellular matrix.

Effect of dexmedetomidine on cognition,immune inflammatory reaction and oxidative stress in lung cancer patients with VATS / 中国基层医药

To investigate the effect of dexmedetomidine on cognition ( MMSE score),immune inflammatory reaction and oxidative stress in lung cancer patients with VATS.Methods From January 2016 to December 2017,89 lung cancer patients underwent VATS in the Second Hospital of Qinhuangdao were randomly divided into the control group (n＝46) and the dexmedetomidine group (n＝43) according to the digital table.The MMES,CD4 and CD8 lymphocytes,inflammatory factors and oxidative stress factors were compared between the two groups before operation (T0) and at 3 hours (T1),12 hours (T2),24 hours (T3) after operation.Results There were no statistically significant differences in MMSE ,CD4 and CD8 lymphocytes,inflammatory factors and oxidative stress factors between the two groups (P＞0.05).At the time points of T1,T2 and T3,MMSE scores decreased in both two groups, but the MMSE score in the dexmedetomidine group was higher than those in the control group [(27.67 ±1.97) points vs.(25.61 ±1.81) points,(26.47 ±1.92) points vs.(24.70 ±2.26) points,(26.16 ± 1.90)pouints vs.(23.41 ±2.33) points,t ＝-2.122,-2.553,-2.528,P ＝0.037,0.012,0.013].The CD8 lymphocyte,inflammatory factors and oxidative stress factors increased after operation in both two groups , and dexmedetomidine could inhibit the increase of immune inflammatory factors and oxidative response factors (IL-6:t＝ 3.038,2.489,3.291,P＝0.003,0.015,0.001;hsCRP:t＝2.147,2.164,2.752,P＝0.035,0.033,0.007;TNF-α:t＝2.119,2.323,2.485,P＝0.037,0.023,0.015;MDA:t＝2.499,2.116,2.094,P＝0.014,0.037,0.039;MPO:t＝2.190,2.166,2.849,P＝0.031,0.033,0.005;SOD:t＝-2.551,-2.598,-3.141,P＝0.012,0.011,0.002). The incidence rate of adverse reactions in dexmedetomidine group was lower than that in control group (6／43 vs. 18／46,P＝0.011).Conclusion Dexmedetomidine can improve cognition ,reduce immune inflammatory reaction and oxidative stress,and alleviate adverse effects in lung cancer patients with VATS.

Research advance of A20 on atherosclerosis / 中国药理学通报

Atherosclerosis, as a chronic inflammatory disease, is the most common one among cardiovascular system disorders. Inflammation is crucial in the development of atherosclerosis, which participates in the entire process of atherosclerosis. NF-κB can target to most inflammatory factors, and excessive NF-κB activation aggravates atherosclerosis development. Previous stud- ies have shown that the zinc finger protein A20 plays a key role in the anti-inflammatory and anti-apoptotic response. Research advances on A20 in protection of atherosclerosis are thus summa-rized in this review.

Study on the Preventive Effect and Mechanism of Wei Medicine Kunlun Snow Chrysanthemum Polysaccha-rides on Carbon Tetrachloride-induced Acute Liver Injury in Mice / 中国药房

OBJECTIVE:To study the preventive effect and mechanism of Wei medicine Kunlun snow chrysanthemum polysac-charides(KSCP)on carbon tetrachloride(CCl4)-induced acute liver injury in mice. METHODS:96 mice were randomly divided in-to normal group(normal saline),model group(normal saline),Biphenyl diester dropping pill(positive control,1.5 mg/10 g)and KSCP low-dose,medium-dose,high-dose groups (0.3,0.6,1.2 mg/10 g),16 in each group,with intragastric administration, once a day,for 10 d. Except for normal group,mice in other groups were intraperitoneally injected 1%CCl4 rapeseed oil solution to induce liver injury. After 24 h of modeling,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),tu-mor necrosis factor α(TNF-α),interleukin 1(IL-1)in serum,levels of malondialdehyde(MDA),superoxide dismutase(SOD) in liver tissue were detected;the liver,spleen indexes were calculated. Pathological changes of liver tissue were observed,patho-logical scoring was conducted. The protein expressions of apoptosis-related genes Caspase-3,Bcl-2,Bax in liver tissue were detect-ed. RESULTS:Compared with normal group,levels of ALT,AST,TNF-α,IL-1 in serum,MDA level in liver tissue and liver, spleen indexes in model group were obviously increased(P<0.01);SOD level in liver tissue was decreased(P<0.01);pathologi-cal changes in hepatocellular necrosis,degeneration and inflammatory cell infiltration,and pathological score in model group was obviously increased(P<0.01);caspase-3 protein expression and Bcl-2/Bax ratio in liver tissue in model group were obviously de-creased (P<0.01). Compared with model group,above-mentioned indexes in each administration group were obviously improved (P<0.05 or P<0.01). CONCLUSIONS:KSCP has certain preventive effect on CCl4-induced acute liver injury in mice,and its mechanism may be associated with anti-oxidation,anti-inflammation and regulation of apoptosis-related protein expressions.

Effect of meloxicam on CUMS-induced depressive-like behavior in rats and its preliminary mechanism / 中国药理学通报

Aim To explore the effect of meloxicam on the CUMS-induced depressive-like behaviors in rats and its preliminary mechanism. Methods The rats were exposed to CUMS procedure for 6 weeks to estab-lish the model of depression. Meloxicam(1,3 mg· kg-1 ) and sertraline(5 mg·kg-1 ) were administered to rats from 22d of the stress procedure(once a day,for 21 days,p. o. ) . Depressive-like behaviors were evalu-ated by the open-field test and force swimming test. The levels of PGE2 and TNF-αin cortex were measured by ELISA. Moreover, the concentrations of NE, DA, DOPAC and 5-HIAA were also measured by HPLC, and the protein expression of 5-HT1 AR in cortex was analyzed by the immunohistochemistry. Results Com-pared with the rats of normal control group,the vertical and horizontal movement scores of rats in the open-field test were decreased and the immobility time in the forced swimming test was increased in model group. The levels of PGE2 and TNF-α were both increased signifi-cantly,whereas the concentrations of NE, DA, DOPAC and 5-HIAA were decreased and the expression of 5-HT1AR was reduced in cortex. Compared with the rats of model group, meloxicam significantly improved the depressive behaviors of rats in experimental groups and reversed the content of PGE2 ,TNF-α,NE,DA,DOPAC and 5-HIAA, as well as the expression of 5-HT1AR. Conclusion Meloxicam has a significant protective effect on CUMS-induced depressive-like behaviors, and the protective mechanism might be related to atten-uating inflammation response and reconstructing the balance of the monoamine neurotransmitter system in rat cortex.

The immunoregulatory effect of Rho kinase inhibitor Fasudil on macrophages in a mouse model of ;experimental autoimmune encephalomyelitis / 中华微生物学和免疫学杂志

Objective To investigate the immunoregulatory effect of Fasudil-modified macrophages on cell transferred experimental autoimmune encephalomyelitis ( EAE) in a mouse model.Methods Fe-male C57BL/6 mice were immunized with MOG35-55 to establish the model of EAE.The encephalomyelitic mononuclear cells ( MNCs) were isolated from spleen of mice with EAE on day 9 after immunization and treated with or without Fasudil for 72 h in vitro.Several assays including the flow cytometry analysis, Griess reaction and ELISA were performed to analyze the M1 and M2 phenotypes of macrophages, the production of NO and the levels of cytokines, respectively.The cultured MNCs (5×107 cells) were resuspended in 500μl of PBS and transferred into na?ve C57BL/6 recipients via intraperitoneal injection.Two groups including the PBS-MNCs group and the Fasudil-MNCs group were set up.The body weights and clinical scores of the mice in each group were recorded in every other days after the induction of EAE in the recipients.Results The Fasudil treated MNCs affected the induction of EAE in adoptive cell transferred mice.The expression of CD16/32, iNOS and IL-12 on F4/80-macrophages were decreased, while the expression of CD206, CD23 and IL-10 on F4/80-macrophages were increased upon the treatment of Fasudil, indicating that Fasudil im-proved the differentiation of macrophages from M1 to M2 phenotypes.Moreover, Fasudil inhibited the pro-duction of NO and enhanced the expression of Arginase-1.Conclusion Fasudil ameliorated the clinical se-verity of EAE in mice by promoting the transformation of macrophages from M1 to M2 phenotype.

Progress in inflammatory pathogenesis of atherosclerosis / 西安交通大学学报(医学版)

both pathogenesis and complications of atherosclerosis.There are three kinds of inflammation in formation and development of atherosclerosis:biological,immunological and chemical inflammation.Vessel wall manifests the acute exudative inflammation in the early stage of atherosclerosis and chronic proliferative inflammation in the progressive stage of atherosclerosis.Many inflammatory cells,inflammatory cytokines and mediators,adhesion molecules,chemotactic factors and growth factors are involved in the inflammatory responses of vessel wall.It has been demonstrated that anti-atherosclerotic drugs used in clinical practice can produce anti-inflammatory effects. Therefore,anti-inflammatory therapy is a new strategy for prevention and treatment of atherosclerosis.

The influence of intestinal dysbacteriosis on visceral sensitivity and possible mechanisms / 西安交通大学学报(医学版)

Objective To detect the changes of visceral sensitivity in rats presenting intestinal dysbacteriosis and the expressions of tight junction protein (ZO-1)and Toll-like receptor 4 (TLR4)so as to explore the effect of intestinal dysbacteriosis on visceral sensitivity and the possible mechanisms.Methods We randomly divided 30 male SD rats of SPF grade into normal control group (n = 12 )and dysbacteriosis group (n = 18 ).Rats in dysbacteriosis group were administered with lincomycin hydrochloride (300 mg/mL),1 mL each time per rat once a day for 7 consecutive days;those in normal control group were fed with the same amount of saline.On the eighth day,six rats were randomly selected from normal control group and dysbacteriosis group respectively to detect whether the model was successful.After the model was successfully constructed,the remaining 12 dysbacteriosis rats were randomly divided into the negative control group and the probiotics intervention group with 6 in each.Rats in the intervention group were given probiotic bifidobacterium triple viable capsules (Bifico)orally,one capsule with 1/3 mL of saline,1 mL each time per rat once a day for 7 consecutive days;those in the negative control group received the same amount of saline.On the eighth day,fresh feces was cultured for flora to detect visceral sensitivity by abdominal withdrawal reflex (AWR),the mRNA and protein expressions of ZO-1 and TLR4 in the colon,and the expression of serum inflammatory cytokines IL-10 and TNFα.Results The expression of ZO-1 in the colon was significantly lower in the rats of dysbacteriosis group than those in the control group,and the expression of TLR4 was also significantly increased.Correspondingly,the expression of pro-inflammatory factor TNFα in the serum of the rats in dysbacteriosis group was significantly increased,while that of anti-inflammatory factor IL-10 was significantly lower than in the control group (P <0.05).Furthermore,compared with dysbacteriosis group,the expression of ZO-1 was increased significantly and TLR4 was decreased in probiotics group in varying degrees. Similarly,the expression of TNFα was obviously lower while that of IL-10 in the serum was higher (P < 0.05 ). Conclusion Inhibiting the expression of ZO-1 and increasing the expression of TLR4,thus leading to chronic low-grade inflammation, may be one mechanism of visceral hypersensitivity caused by intestinal dysbacteriosis. Probiotics may restore the dysbacteriosis and thus improve visceral hypersensitivity.

Atorvastatin attenuates activation and injury of human microvascular endothelial cells induced by oxidized low density lipoprotein / 中国药理学通报

Aim To investigate the effects of atorvas-tatin ( ATV) on activation and injury of microvascular endothelial cells induced by oxidized low density lipo-protein ( ox-LDL) . Methods Cultured human micro-vascular endothelial cells were pre-incubated with ATV for 24 h prior to exposure of endothelial cells to ox-LDL. After exposure of endothelial cells to ox-LDL, the cell viability was measured by MTT method, LDH in supernatants was determined by enzyme activity as-say kit, ICAM-1 in supernatants was assayed by using ELISA method, phosphorylation of NF-κB p65 was de-tected by western blot analysis, transcriptional activity of NF-κB signal pathway was measured by employing dual-luciferase reporter assay system. Results Hu-man microvascular endothelial cells were activated and injured by ox-LDL. Inhibition of the cell viability, re-lease of LDH, expression of ICAM-1, phosphorylation of NF-κB p65 , and up-regulated transcriptional activity of NF-κB induced by ox-LDL were attenuated by ATV. Conclusion ATV can significantly inhibit the activa-tion and injury of human microvascular endothelial cells induced by ox-LDL, and that may be related to inhibition of phosphorylation and transcriptional activity of NF-κB.

Expression profile of inflammation related genes in laryngeal cancer / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the expression profile of inflammation related genes in laryngeal squamous cell carcinoma by functional gene chip technique and to probe into the role of correlative genes in pathogenesis of the laryngeal squamous cell cancer and in tumor immunity. METHODS The total RNAs were respectively extracted from two pair samples of laryngeal tumor and the normal tissue around the tumor, and then were reversely transcribed to cDNAs, then synthesized to cRNAs. The cRNAs were labeled with the hybridization probes. The probes were then hybridized with four pieces of inflammation related genes chip. It was chemiluminescently detected and the acquired image was analyzed with special software. RESULTS Forty genes were differently expressed in inflammation related gene profile of laryngeal tumor, among which 22 genes were upregulated and 18 genes were down regulated. Thirteen genes were shown differential expression in both chips with 10 upregulated genes and 3 downregulated genes. CONCLUSION The differently expressed genes in inflammation related gene chips will provide clues and theoretical foundation for the investigation of the relationship between tumor and inflammation, and also the immune pathogenesis of laryngeal tumor. Furthermore CCL-7 may have an important role in the occurrence of laryngeal cancer, and the role of immunity of the pathogenesis of laryngeal tumor needs further studied.

Anti -allergic Effects of Xitare Tab lets Combined with External Applica tion of Xitare Ointment / 中药新药与临床药理

Objective To investigate the anti -allergic effects of Xitare tablets combined with external use of Xitare Oint-3Gussinye Mment.MethodsSynlogousratmodelsofdermalsensitivity,mousemodelsofDNCB-induceddelayedhypersensitivity,ratmodelsofmastocyticdegranulationandguineapigmodelsofhistamine-phosphate-induceditchingreactionwereap-plied.ResultsXitaretablets(1.75,3.5,7.0g/kgbodyweight,bid,ig)combinedwithexternaluseofXitareOint-ment(0.7,1.4,2.1g/pertime,qd)obviouslycounteractedtheallergicreactioninratswithdermalsensitivity(P