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Objectives To investigate the ameliorative effect of cannabinoid 2 receptor(CB2R)agonist JWH-015 on the cog-nitive impairment of Alzheimer' s disease(AD)model mice and to assess the correlation with microglial phenotype transformation. Methods Twenty adult male C57BL/6J mice were randomly divided into four groups:C57BL/6J solvent group,JWH-015 control group,AD model group,and AD model treated with JWH-015 group. Amyloidβ1-42 oligomers of 4μg and the same volume of saline were intraventricularly administered to construct the AD mouse model and the solvent groups. CB2R agonist JWH-015 or the corre-sponding vehicle at a dose of 0.5 mg/(kg·d)was administered by intraperitoneal injection for 3 weeks. Non-spatial learning and memo-ry was measured using novel object recognition task. Furthermore,the mRNA expression levels of M1 microglia marker inducible ni-tric oxide synthase(iNOS)and M2 microglia marker chitinase-3 like protein(Ym1/2)in brain samples of cortex and hippocampus were evaluated using real-time quantitative PCR(qPCR). In the meantime,fifteen CB2R knockout(CB2RKO)mice and five CB2R wild-type(CB2RWT)littermates were assigned to identify the specificity of CB2R in the research. Based on the genotype and different treatment,the animals were divided into four groups:CB2RKO solvent group,CB2RKO AD model group,CB2RKO AD model treat-ed with JWH-015 group and CB2RWT solvent group. Results Compared with solvent group,there was a significant decrease in nov-el object recognition index in C57BL/6J AD model group(P<0.01). The mRNA expression levels of M1 phenotype microglia marker iNOS in cortex and hippocampus were significantly up-regulated(both P<0.05)and the mRNA expression levels of M2 phenotype mi-croglia marker Ym1/2 were significantly down-regulated(both P<0.01). Interestingly,administration of JWH-015 could reverse the impairment of novel object recognition index(P<0.05);compared with C57BL/6J AD model group,administration of JWH-015 also decreased the iNOS mRNA expression levels(both P<0.05)and increased the Ym1/2 mRNA expression levels(both P<0.05)in cortex and hippocampus;compared with CB2RKO solvent group,the novel object recognition index of CB2RKO AD model group was decreased(P<0.05);the mRNA expression levels of iNOS in cortex and hippocampus were significantly up-regulated(both P<0.05),the mRNA expression level of Ym1/2 in cortex was significantly down-regulated in cortex(P<0.05);compared with CB2RKO AD model group,administration of JWH-015 had no effect on novel object recognition index and the mRNA expression level of M1/M2 in cortex and hippocampus,respectively. Conclusion JWH-015 improves the cognitive impairment of Aβ-induced AD mice by the specific activation of CB2R,the mechanism of which is related to the direct regulation of CB2R on the M1/M2 microglial phenotype transformation and microglia-mediated neuroinflammation in brain.
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Objective:To evaluate the clinical effects of nicardipine for induced controlled hypotension in patients underwent orthognathic surgery.Methods:The related trails were searched from English and Chinese literature databases.The quality of the RCTs was evaluated by 2 indepandent reviewers.The data were statistical analyzed using the Rev Man 5.3.3 software.Results:5 RCTs with 248 patients were included.Meta-analysis and descriptive analysis indicated that blood loss of nicardipine group was more than that of remifentanil group [WMD =43.85,95％ CI(20.52,67.18)].There was no significant difference in blood loss between nicardipine group and dexmedetomidine group and nitroglycerin group.There was no significant difference in transfusion between nicardipine group and the control group.Nicardipine increased the heart rate during controlled hypotension and caused QT prolongation (P ＜ 0.001).Nicardipine had no adverse effects on cerebral oxygen saturation and neurophysiological function.Urinary N-acetyl-1-b-D-glucosaminidase was lower in nicardipine group than that in remifentanil group (P ＜ 0.05).Conclusion:Nicaridpine is effective in the induced controlled hypotension during orthognathic surgery,with potential renal protective effect.However,it is not better than the remifentanil on reducing the blood loss.Nicardipine can increase the heart rate and prolong the QT interval during the controlled hypotension.
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Objective To evaluate the ameliorative effect of telmisartan on the inflammatory reaction induced by lipopolysaccharide(LPS) in microglia cells and investigate its effect on modulation of activated microglia phenotype transformation by activation of the peroxisome proliferator-activated receptor γ (PPARγ) accordingly. Methods The PPARγ agonistic activity of telmisartan was explored using PPARγ-responsive element- lucifarase reporter assay ,and inflammatory model was established through LPS-induced microglia cells. The mice microglia cells (BV-2 microglia cell line) were treated in the presence of telmisartan ranging from 0.1 to 10 μmol/L or in the presence of 1 mol/L telmisartan with 10 μmol/L GW9662, the specific PPARγ antagonist. The contents of tumor necrosis factor-alpha (TNF-α ) in cell supernatants were analyzed by ELISA; the mRNA expression level of M1 phenotype markers CD16, CD11b and iNOS as well as M2 phenotype marker IL-10 were evaluated using the real-time quantitative PCR. Results Compared with control group, telmisartan could concentration-dependently activate the PPARγ ranging from 0.1 to 10 μmol/L and the relative lucifarase activity induced by telmisartan was 1.29, 1.36 and 1.45 folds (P<0.01), respectively; in the inflammatory model of BV-2 cells induced by LPS, compared with control group, the content of TNF-α in cell supernatants significantly increased (P<0.01) and the mRNA expression level of M1 phenotype microglia markers CD16, CD11b and iNOS was significantly up-regulated (P<0.05) in LPS group; compared with LPS group, telmisartan could concentration-dependently decreased the content of TNF-α in cell supernatants arranging from 0.1 to 10 mol/L (P<0.05); 10 mol/L telmisartan could significantly down-regulated the mRNA expression level of M1 phenotype microglia markers CD16, CD11b and iNOS (P<0.01, P<0.05 and P<0.05) ; additionally, 0.1 μmol/L telmisartan could significantly up-regulated the mRNA expression level of M2 phenotype microglia marker IL-10 (P<0.05); compared with 1 mol/L telmisartan treated group, the mRNA expression level of CD16 was significantly up-regulated by specific PPARγ antagonist GW9662 (P<0.05). Conclusion Telmisartan could markedly reduce the release of TNF-α in LPS-induced activated microglia cells; the mechanism is associated with modulating the transformation of M1/M2 microglia phenotype by the activation of PPARγ.
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Firstly, kneading patient's shoulder joint to relax the muscles and relieve adhesion, then applying joint relaxing manipulation, 82 cases with scapulohumeral periarthritis were treated with these methods, 50 cases were cured, 12 cases got marked effectiveness, 16 cases improved, 4 cases no effect, and the total effective rate was 95.1%.
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Acupuncture was performed at points in the upper-jiao and lower-jiao areas of two eyes and scalp acupuncture, in the motor area on the healthy side. Thirty-four patients with apoplectic sequela were treated. The total efficacy rate was 97.0%.