目的:观察MK801对豚鼠近视的调节,探讨其在近视发病机制中的作用。方法:3周龄三色豚鼠分为6组:A组(正常空白对照组)、B组(右眼遮盖3周组)、C组(右眼遮盖3周+玻璃体腔生理盐水注射组)、D组(右眼遮盖3周+玻璃体腔注射1 ng MK801组)、E组(...目的:观察MK801对豚鼠近视的调节,探讨其在近视发病机制中的作用。方法:3周龄三色豚鼠分为6组:A组(正常空白对照组)、B组(右眼遮盖3周组)、C组(右眼遮盖3周+玻璃体腔生理盐水注射组)、D组(右眼遮盖3周+玻璃体腔注射1 ng MK801组)、E组(右眼遮盖3周+玻璃体腔注射10 ng MK801组)、F组(右眼遮盖3周+玻璃体腔注射100 ng MK801组)。实验前及实验3周时对各组进行视网膜检影和A超测眼轴,原位杂交法检测神经细胞性一氧化氮合酶(ncNOS)的表达,放射免疫法检测cGMP的含量,将D,E,F组的屈光度、眼轴、ncNOS及cGMP含量与MK801药物浓度进行直线相关分析。结果:玻璃体腔药物注射C,D,E,F组遮盖眼随注射浓度的升高近视屈光度数下降,眼轴延长减慢,ncNOS及cGMP含量下调,与MK801注射浓度行相关分析呈直线相关,屈光度与注射浓度呈正相关(r=0.702,P<0.05),眼轴长度、ncNOS表达、cGMP表达与其呈负相关(r=-0.736,-0.637,-0.725,P<0.05)。结论:近视豚鼠MK801玻璃体腔注射能通过下调NO-cGMP表达减缓近视的进展,呈剂量依赖性。展开更多
Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(N...Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BPinduced cognitive dysfunction. Male Wistar rats were administered with MK801(0.1 mg/kg) prior to 1-BP intoxication(800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological,and immunological analyses. We found that the spatial learning and memory were significantly impaired in the1-BP group, and this was associated with neurodegeneration in both the hippocampus(especially CA1 and CA3)and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex.Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.展开更多
文摘目的:观察MK801对豚鼠近视的调节,探讨其在近视发病机制中的作用。方法:3周龄三色豚鼠分为6组:A组(正常空白对照组)、B组(右眼遮盖3周组)、C组(右眼遮盖3周+玻璃体腔生理盐水注射组)、D组(右眼遮盖3周+玻璃体腔注射1 ng MK801组)、E组(右眼遮盖3周+玻璃体腔注射10 ng MK801组)、F组(右眼遮盖3周+玻璃体腔注射100 ng MK801组)。实验前及实验3周时对各组进行视网膜检影和A超测眼轴,原位杂交法检测神经细胞性一氧化氮合酶(ncNOS)的表达,放射免疫法检测cGMP的含量,将D,E,F组的屈光度、眼轴、ncNOS及cGMP含量与MK801药物浓度进行直线相关分析。结果:玻璃体腔药物注射C,D,E,F组遮盖眼随注射浓度的升高近视屈光度数下降,眼轴延长减慢,ncNOS及cGMP含量下调,与MK801注射浓度行相关分析呈直线相关,屈光度与注射浓度呈正相关(r=0.702,P<0.05),眼轴长度、ncNOS表达、cGMP表达与其呈负相关(r=-0.736,-0.637,-0.725,P<0.05)。结论:近视豚鼠MK801玻璃体腔注射能通过下调NO-cGMP表达减缓近视的进展,呈剂量依赖性。
基金supported by the National Natural Science Foundation of China(81872654,81703264)Fundamental Research Funds of Shandong University(2016JC020),ChinaNatural Science Foundation of Shandong Province(ZR2017MH002),China
文摘Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BPinduced cognitive dysfunction. Male Wistar rats were administered with MK801(0.1 mg/kg) prior to 1-BP intoxication(800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological,and immunological analyses. We found that the spatial learning and memory were significantly impaired in the1-BP group, and this was associated with neurodegeneration in both the hippocampus(especially CA1 and CA3)and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex.Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.
