OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was ...OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.展开更多
To improve aqueous solubility and anti-ischemic activity of 3-n-butylphthalide(NBP),we designed and synthesized the ring-opened derivative of NBP-ferulic acid-glucose trihybrids(S1-S8).These hybrids inhibited adenosin...To improve aqueous solubility and anti-ischemic activity of 3-n-butylphthalide(NBP),we designed and synthesized the ring-opened derivative of NBP-ferulic acid-glucose trihybrids(S1-S8).These hybrids inhibited adenosine diphosphate(ADP)-or arachidonic acid(AA)-induced platelet aggregation,among them,S2 was 30-fold more water-soluble,and over 10-fold more potent in inhibition of platelet aggregation,as well as reduced ROS generation and protected primary neuronal cells from OGD/Rinduced damage,in comparison with NB P.Additionally,S2 was more active than its three moieties alone or in combination,suggesting that the activity of S2 may be attributed to the synergistic effects of these moieties.Importantly,in vivo studies indicated that S2 not only possessed good pharmacokinetic profile,but also improved NBP distribution in rodent brain,suggesting that the glucose moiety in S2 may be recognized by glucose transporter 1(GLUT1)on blood-brain barrier(BBB),promoting it to penetrate through BBB.Our findings suggest that S2 may be a promising candidate for the intervention of ischemic stroke,warranting further study.展开更多
基金The project supported by National Natural Science Foundation of China(81302760)the Chinese Postdoctoral Science Foundation Project(2013M542510)
文摘OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.
文摘【目的】探讨手足口病不同临床分期（1、2、3、4期）肿瘤坏死因子（tumor necrosis factor ，TNF）、白介素-6（IL-6）及B型脑钠肽（BNP）的变化特点，为临床评估此类患者提供参考。【方法】选择2011年5月至2013年10月在本院就诊的手足口病患儿292例（其中1期156例，2期106例，3期20例，4期10例），于患儿入院24 h内抽血行TNF、IL-6、BNP检测。观察比较不同分期手足口病患儿细胞因子及BNP的变化特点。【结果】各期TNF、IL-6、BNP水平均较健康对照组明显增高，2期、3期患儿TNF、IL-6、BNP水平明显高于1期，4期的TNF、IL-6、BNP水平明显高于2期、3期水平，且差异相比较均有显著性（ P ＜0．05）。2、3期TNF、IL-6、BNP水平相比较差异无显著性（ P ＞0．05）。【结论】随着患儿病情加重，TNF、IL-6及BNP水平随之相应增高，TNF、IL-6及BN P水平可用于手足口病患儿病情评估的参考指标。
文摘目的:探讨美托洛尔对慢性心力衰竭 (CHF) 患者脑钠肽 (BNP) 水平和心功能的影响.方法:已接受常规治疗,纽约心脏病协会(NYHA)分级标准心功能Ⅱ～Ⅲ级的CHF患者90例,随机分为两组:治疗组(50例),对照组(40例).治疗组在常规治疗基础上加用美托洛尔,从小剂量(6.25 mg,2次/d)逐渐加至靶剂量(50 mg,2次/d),治疗6个月.对比分析治疗前后两组患者的血浆BNP水平、NYHA分级、心率、血压、超声心动图等指标.结果:治疗组较对照组左室舒张末期内径[(63±7)mm vs (59±5) mm)]、左室收缩末期内径[(53±8) vs (47±4) mm)]和左室质量指数[(160±24)g/m2 vs (135±18) g/m2)]显著下降(均P<0.05),左室射血分数(LVEF)显著升高[(38±11)% vs (47±9)%](P<0.05),血浆BNP[(121±54)ng/L vs (70±9)ng/L)]显著降低(P<0.05);另外,美托洛尔治疗前后患者血浆BNP降低值与左室舒张末期内径(r=0.80)、左室收缩末期内径(r=0.79)和左室质量指数(r=0.71) 减少呈正相关 (均P<0.01),而与LVEF的增加呈负相关(r=-0.86,P<0.01).结论:美托洛尔能抑制CHF患者神经内分泌的过度激活,阻断CHF的发展进程,改善心功能,血浆BNP可作为评价β受体阻滞剂治疗CHF疗效的监测指标之一.
基金the National Natural Science Foundation of China(Nos.81773573,81822041,21977116 and 81673305)National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”(No.2018ZX09711002006-013)+2 种基金the open project of State Key Laboratory of Natural Medicines(No.SKLNMZZCX201824)State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund(No.SKL-HIDCA-2018-1)Part of the work was supported by Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX18_0795)。
文摘To improve aqueous solubility and anti-ischemic activity of 3-n-butylphthalide(NBP),we designed and synthesized the ring-opened derivative of NBP-ferulic acid-glucose trihybrids(S1-S8).These hybrids inhibited adenosine diphosphate(ADP)-or arachidonic acid(AA)-induced platelet aggregation,among them,S2 was 30-fold more water-soluble,and over 10-fold more potent in inhibition of platelet aggregation,as well as reduced ROS generation and protected primary neuronal cells from OGD/Rinduced damage,in comparison with NB P.Additionally,S2 was more active than its three moieties alone or in combination,suggesting that the activity of S2 may be attributed to the synergistic effects of these moieties.Importantly,in vivo studies indicated that S2 not only possessed good pharmacokinetic profile,but also improved NBP distribution in rodent brain,suggesting that the glucose moiety in S2 may be recognized by glucose transporter 1(GLUT1)on blood-brain barrier(BBB),promoting it to penetrate through BBB.Our findings suggest that S2 may be a promising candidate for the intervention of ischemic stroke,warranting further study.
