Objective:To investigate the effects of electroacupuncture(EA)on the blood-brain barrier permeability and the regulation of matrix metalloproteinases(MMPs)in the mice with Parkinson’s disease(PD).Methods:Forty-eight ...Objective:To investigate the effects of electroacupuncture(EA)on the blood-brain barrier permeability and the regulation of matrix metalloproteinases(MMPs)in the mice with Parkinson’s disease(PD).Methods:Forty-eight C57BL/6 mice were randomly assigned into the normal control(NC)group,the PD model(PD)group,the EA group and the EA+SB-3CT inhibitor group(EA+SB-3CT),with 12 mice in each group.In this experiment,the PD model was established by intragastric administration(IG)with rotenone for 4 wk in the PD group,EA group and EA+SB-3CT group.In the EA+SB-3CT group,1 h after IG with rotenone,the mice were intraperitoneally injected with MMP-2/9 inhibitor,SB-3CT(25 mg/kg/d).After successfully modeled,in the EA group and EA+SB-3CT group,EA was conducted at“Fengfu(GV16)”and bilateral“Taichong(LR3)”and“Zusanli(ST36)”,at 1 mA and 2 Hz for 30 min each time,once a day,for consecutive 2 wk.The behavioral changes of the mice were observed in each group using the open field test,the level of tyrosine hydroxylase(TH)in the substantia nigra was determined by immunohistochemistry,the permeability of the blood-brain barrier was detected by Evans blue staining,and the protein expression of ZO-1,ocludin,claudin-1,MMP-2 and MMP-9 in the substantia nigra was detected by Western blotting.Results:Compared with the NC group,the behavioral scores increased(P<0.05),while total time of locomotion,total distance and average speed were reduced(P<0.05)in the PD group.The expression of TH in the substantia nigra decreased(P<0.05),Evans blue level in the brain tissue increased(P<0.05),and the protein expression of ZO-1,occludin and claudin-1 was lower(P<0.05),whereas MMP-2 and MMP-9 expression was higher(P<0.05)in the PD group.Compared with the PD group,behavioral scores decreased(P<0.05),while the total time of locomotion,total distance and average speed increased(P<0.05)in the EA group.Additionally,TH expression in the substantia nigra was elevated(P<0.05),Evans blue level in the brain tissue was lower(P<0.05),the protein expression of ZO-1,occludin and claudin-1 was up-regulated(P<0.05),and MMP-2 and MMP-9 expression was down-regulated(P<0.05)in the EA group.Compared with the EA group,Evans blue level was reduced(P<0.05),the protein expression of ZO-1 and occludin was up-regulated(P<0.05),and MMP-2 and MMP-9 expression was further down-regulated(P<0.05)in the EA+SB-3CT group.Conclusion:EA can effectively ameliorate the motor dysfunction of PD mice,reduce the damage of dopaminergic neurons,and play a neuroprotective role.EA can effectively improve the blood–brain barrier permeability in PD mice by up-regulating the expression of tight junction proteins,ZO-1 and occludin,and down-regulating the expression of matrix metalloporteinases,MMP-2 and MMP-9.The neuroprotective role of EA may be obtained by improving the blood-brain barrier permeability mediated by MMP-2/9 pathway.展开更多
目的研究血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-26(MMP-26)、基质金属蛋白酶抑制剂-4(TIMP-4)与弥漫大B细胞淋巴瘤(Diffuse large B celllymphoma,DLBCL)病理分期及预后的相关性。方法选取2021年1月1日至2022年4月1日于上海交...目的研究血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-26(MMP-26)、基质金属蛋白酶抑制剂-4(TIMP-4)与弥漫大B细胞淋巴瘤(Diffuse large B celllymphoma,DLBCL)病理分期及预后的相关性。方法选取2021年1月1日至2022年4月1日于上海交通大学医学院附属瑞金医院治疗的75例DLBCL患者为研究组,另选取75例淋巴结反应性增生患者作为对照组,观察研究组与对照组及研究组不同分期、不同发病部位血清MMP-9、MMP-26及TIMP-4水平;采用Spearman分析DLBCL患者血清MMP-9、MMP-26与TIMP-4间的相关性;绘制Kaplan-Meier生存曲线,分析MMP-9、MMP-26、TIMP-4水平与DLBCL患者预后的关系。结果研究组血清MMP-9、MMP-26水平均高于对照组,血清TIMP-4水平均低于对照组,差异有统计学意义(P<0.05)。研究组Ⅰ~Ⅱ期患者血清MMP-9、MMP-26水平低于Ⅲ~Ⅳ期患者,血清TIMP-4水平高于Ⅲ~Ⅳ期患者,差异有统计学意义(P<0.05)。研究组不同发病部位患者血清MMP-9、MMP-26、TIMP-4水平比较差异均无统计学意义(P>0.05)。DLBCL患者血清MMP-9、MMP-26水平与TIMP-4水平呈负相关(P<0.05);血清MMP-9水平与MMP-26水平正相关(P<0.05)。MMP-9和MMP-26高表达、TIMP-4低表达组患者累积生存率低于其他组患者,差异具有统计学意义(P<0.05)。结论血清MMP-9、MMP-26及TIMP-4水平与DLBCL病理分期及患者预后密切相关,检测血清MMP-9、MMP-26及TIMP-4水平有助于明确DLBCL病理分期及评价患者预后。展开更多
慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD,慢阻肺)是一种由气道炎症和气道重塑(airway remodeling, AR)引起的一种常见的慢性呼吸系统疾病。其中,气道重塑与COPD的进展之间存在的正反馈环显示了气道重塑在COPD进...慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD,慢阻肺)是一种由气道炎症和气道重塑(airway remodeling, AR)引起的一种常见的慢性呼吸系统疾病。其中,气道重塑与COPD的进展之间存在的正反馈环显示了气道重塑在COPD进展中的重要性。目前气道重塑的具体机制不明。临床上通过胸部CT发现的气道异常常提示患者已经发生了气道重塑,因此,寻找识别早期气道重塑的方法至关重要。研究表明,基质金属蛋白酶-9 (matrix metalloproteinase-9, MMP-9)、金属蛋白酶组织抑制剂-1 (tissue inhibitor of metalloproteinase-1, TIMP-1)、及MMP-9/TIMP-1比值之间的失衡参与COPD的气道重塑过程,本文叙述了MMP-9、TIMP-1及MMP-9/TIMP-1比值作为非侵入性诊断标志物在COPD气道重塑方面的研究进展,期待能提高人们对早期气道重塑的认知,希望能为将来气道重塑靶向药的问世尽一份绵薄之力。Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease caused by airway inflammation and airway remodeling (AR). Among them, the positive feedback loop between airway remodeling and the progression of COPD shows the importance of airway remodeling in the progress of COPD. At present, the specific mechanism of airway remodeling is unknown. Airway abnormalities found by chest CT often indicate that airway remodeling has occurred in patients. Therefore, it is very important to find a method to identify early airway remodeling. Studies have shown that the imbalance between matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and MMP-9/TIMP-1 ratio is involved in the airway remodeling of COPD. This paper describes the research progress of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio as non-invasive diagnostic markers in airway remodeling of COPD. It is expected to improve people’s understanding of early airway remodeling and make a modest contribution to the development of targeted drugs for airway remodeling in the future.展开更多
基金Supported by National Natural Science Foundation of China:No.8147378。
文摘Objective:To investigate the effects of electroacupuncture(EA)on the blood-brain barrier permeability and the regulation of matrix metalloproteinases(MMPs)in the mice with Parkinson’s disease(PD).Methods:Forty-eight C57BL/6 mice were randomly assigned into the normal control(NC)group,the PD model(PD)group,the EA group and the EA+SB-3CT inhibitor group(EA+SB-3CT),with 12 mice in each group.In this experiment,the PD model was established by intragastric administration(IG)with rotenone for 4 wk in the PD group,EA group and EA+SB-3CT group.In the EA+SB-3CT group,1 h after IG with rotenone,the mice were intraperitoneally injected with MMP-2/9 inhibitor,SB-3CT(25 mg/kg/d).After successfully modeled,in the EA group and EA+SB-3CT group,EA was conducted at“Fengfu(GV16)”and bilateral“Taichong(LR3)”and“Zusanli(ST36)”,at 1 mA and 2 Hz for 30 min each time,once a day,for consecutive 2 wk.The behavioral changes of the mice were observed in each group using the open field test,the level of tyrosine hydroxylase(TH)in the substantia nigra was determined by immunohistochemistry,the permeability of the blood-brain barrier was detected by Evans blue staining,and the protein expression of ZO-1,ocludin,claudin-1,MMP-2 and MMP-9 in the substantia nigra was detected by Western blotting.Results:Compared with the NC group,the behavioral scores increased(P<0.05),while total time of locomotion,total distance and average speed were reduced(P<0.05)in the PD group.The expression of TH in the substantia nigra decreased(P<0.05),Evans blue level in the brain tissue increased(P<0.05),and the protein expression of ZO-1,occludin and claudin-1 was lower(P<0.05),whereas MMP-2 and MMP-9 expression was higher(P<0.05)in the PD group.Compared with the PD group,behavioral scores decreased(P<0.05),while the total time of locomotion,total distance and average speed increased(P<0.05)in the EA group.Additionally,TH expression in the substantia nigra was elevated(P<0.05),Evans blue level in the brain tissue was lower(P<0.05),the protein expression of ZO-1,occludin and claudin-1 was up-regulated(P<0.05),and MMP-2 and MMP-9 expression was down-regulated(P<0.05)in the EA group.Compared with the EA group,Evans blue level was reduced(P<0.05),the protein expression of ZO-1 and occludin was up-regulated(P<0.05),and MMP-2 and MMP-9 expression was further down-regulated(P<0.05)in the EA+SB-3CT group.Conclusion:EA can effectively ameliorate the motor dysfunction of PD mice,reduce the damage of dopaminergic neurons,and play a neuroprotective role.EA can effectively improve the blood–brain barrier permeability in PD mice by up-regulating the expression of tight junction proteins,ZO-1 and occludin,and down-regulating the expression of matrix metalloporteinases,MMP-2 and MMP-9.The neuroprotective role of EA may be obtained by improving the blood-brain barrier permeability mediated by MMP-2/9 pathway.
文摘目的研究血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-26(MMP-26)、基质金属蛋白酶抑制剂-4(TIMP-4)与弥漫大B细胞淋巴瘤(Diffuse large B celllymphoma,DLBCL)病理分期及预后的相关性。方法选取2021年1月1日至2022年4月1日于上海交通大学医学院附属瑞金医院治疗的75例DLBCL患者为研究组,另选取75例淋巴结反应性增生患者作为对照组,观察研究组与对照组及研究组不同分期、不同发病部位血清MMP-9、MMP-26及TIMP-4水平;采用Spearman分析DLBCL患者血清MMP-9、MMP-26与TIMP-4间的相关性;绘制Kaplan-Meier生存曲线,分析MMP-9、MMP-26、TIMP-4水平与DLBCL患者预后的关系。结果研究组血清MMP-9、MMP-26水平均高于对照组,血清TIMP-4水平均低于对照组,差异有统计学意义(P<0.05)。研究组Ⅰ~Ⅱ期患者血清MMP-9、MMP-26水平低于Ⅲ~Ⅳ期患者,血清TIMP-4水平高于Ⅲ~Ⅳ期患者,差异有统计学意义(P<0.05)。研究组不同发病部位患者血清MMP-9、MMP-26、TIMP-4水平比较差异均无统计学意义(P>0.05)。DLBCL患者血清MMP-9、MMP-26水平与TIMP-4水平呈负相关(P<0.05);血清MMP-9水平与MMP-26水平正相关(P<0.05)。MMP-9和MMP-26高表达、TIMP-4低表达组患者累积生存率低于其他组患者,差异具有统计学意义(P<0.05)。结论血清MMP-9、MMP-26及TIMP-4水平与DLBCL病理分期及患者预后密切相关,检测血清MMP-9、MMP-26及TIMP-4水平有助于明确DLBCL病理分期及评价患者预后。
文摘慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD,慢阻肺)是一种由气道炎症和气道重塑(airway remodeling, AR)引起的一种常见的慢性呼吸系统疾病。其中,气道重塑与COPD的进展之间存在的正反馈环显示了气道重塑在COPD进展中的重要性。目前气道重塑的具体机制不明。临床上通过胸部CT发现的气道异常常提示患者已经发生了气道重塑,因此,寻找识别早期气道重塑的方法至关重要。研究表明,基质金属蛋白酶-9 (matrix metalloproteinase-9, MMP-9)、金属蛋白酶组织抑制剂-1 (tissue inhibitor of metalloproteinase-1, TIMP-1)、及MMP-9/TIMP-1比值之间的失衡参与COPD的气道重塑过程,本文叙述了MMP-9、TIMP-1及MMP-9/TIMP-1比值作为非侵入性诊断标志物在COPD气道重塑方面的研究进展,期待能提高人们对早期气道重塑的认知,希望能为将来气道重塑靶向药的问世尽一份绵薄之力。Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease caused by airway inflammation and airway remodeling (AR). Among them, the positive feedback loop between airway remodeling and the progression of COPD shows the importance of airway remodeling in the progress of COPD. At present, the specific mechanism of airway remodeling is unknown. Airway abnormalities found by chest CT often indicate that airway remodeling has occurred in patients. Therefore, it is very important to find a method to identify early airway remodeling. Studies have shown that the imbalance between matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and MMP-9/TIMP-1 ratio is involved in the airway remodeling of COPD. This paper describes the research progress of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio as non-invasive diagnostic markers in airway remodeling of COPD. It is expected to improve people’s understanding of early airway remodeling and make a modest contribution to the development of targeted drugs for airway remodeling in the future.
