目的探讨创伤后应激障碍（Post-traumatic stress disorder，PTSD）对酒精条件性位置偏爱（conditioned place preference，CPP）获得的易化作用及其多巴胺机制。方法Sprague．Dawley（SD）雄性大鼠40只分为PTSD＋酒精（PE）组、正常对...目的探讨创伤后应激障碍（Post-traumatic stress disorder，PTSD）对酒精条件性位置偏爱（conditioned place preference，CPP）获得的易化作用及其多巴胺机制。方法Sprague．Dawley（SD）雄性大鼠40只分为PTSD＋酒精（PE）组、正常对照＋酒精（CE）组、PTSD＋生理盐水（PS）组和正常对照＋生理盐水（CS）组，每组大鼠进行CPP训练，酒精组给予腹腔注射20％酒精2g／kg，生理盐水组给予相同体积的生理盐水。PTSD动物模型建立采用单一持续性刺激（SPS）方式，通过僵立反应和高架十字迷宫分别测试SPS24h、7d的恐惧记忆及焦虑行为，在SPS7d检测训练后CPP值，并用免疫组织化学方法测定大鼠杏仁核区域多巴胺D1受体的表达。结果与正常对照组比较，仅在SPS7d时PTSD组大鼠僵立时间显著延长[（89．13±8．60）S，（22．25±5．85）S，q=8．77，P〈0．01]；以及进入开放臂次数、时间明显降低[（4．25±1．26）次，（14.38±2.18）次，（12．38＋-3．30）S，（40．38±7．29）S，q分别为4．74和4．08，均P〈0．01]；CPP测试中PE组训练后CPP值明显高于训练前，差异有统计学意义（q=31．81，P〈0．01），其余CE、PS及CS组训练前后CPP值均差异无统计学意义（q分别为1．53，0．01，0．27，P〉0．05）；PE组训练后的CPP值明显高于CS组、CE组和PS组（q分别为-38．32，-22．21，-33．38，P〈0．05）。SPS7d4组大鼠杏仁核区域多巴胺D1受体阳性细胞数免疫组化评分差异无统计学意义（F=0．07，P〉0．05）。结论PTSD样大鼠易于形成酒精条件性位置偏爱，可能与杏仁核多巴胺D1受体数量变化无关。展开更多
AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,a...AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,and the high myopia was diagnosed by optometry,the diopter was less than-6.00 D,and CNV was induced by 532 nm laser.The changes of dopamine D1 receptor(DRD1),dopamine D2 receptor(DRD2),and vascular endothelial growth factor A(VEGFA)were detected by Western blot technology at 0.5,1,2h,and 7d after 0.01%,0.05%,and 0.1%atropine eye drops,respectively,the area of CNV was measured.RESULTS:Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group,and the higher the concentration,the more significant the inhibitory effect(P<0.05).CONCLUSION:The 0.01%,0.05%,0.1%atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1,and the effect of 0.05%and 0.1%atropine eye drops is more significant.展开更多
Breast cancer is the most common cancer in females with extremely high lethality mainly due to the occurrence of metastasis,which is closely related to cancer stem-like cells(CSCs).It has been reported that CSC freque...Breast cancer is the most common cancer in females with extremely high lethality mainly due to the occurrence of metastasis,which is closely related to cancer stem-like cells(CSCs).It has been reported that CSC frequency in drug-resistant breast cancer and non-small cell lung cancer is reduced by activating dopamine D1 receptor(D1 DR).In the present study,we aimed to investigate the effect of a compound C17 that can be used orally for breast cancer metastasis as well as the underlying mechanism involving the activation of D1 DR.The confocal immunofluorescence analysis demonstrated that D1 DR was up-regulated by C17.The cell survival and colony formation were inhibited by C17 through the detection by Sulforhodamine B colorimetric(SRB)assay and colony formation assay,respectively.Results from both wound healing assay and transwell assay demonstrated that C17 inhibited the migration of 4T1 cells.Flow cytometry analysis indicated that C17 significantly reduced the CSC frequency.In addition,C17 could inhibit the lung metastasis in 4T1 orthotopic mouse model of breast cancer without obvious toxicity,and it could up-regulate the expression of intratumoral E-cadherin and down-regulate the expressions of Snail and N-cadherin in primary breast tumor,which might be related to the activation of D1 DR.Our findings provided a potential candidate compound for the treatment of metastatic breast cancer with good compliance and safety.展开更多
文摘目的探讨创伤后应激障碍（Post-traumatic stress disorder，PTSD）对酒精条件性位置偏爱（conditioned place preference，CPP）获得的易化作用及其多巴胺机制。方法Sprague．Dawley（SD）雄性大鼠40只分为PTSD＋酒精（PE）组、正常对照＋酒精（CE）组、PTSD＋生理盐水（PS）组和正常对照＋生理盐水（CS）组，每组大鼠进行CPP训练，酒精组给予腹腔注射20％酒精2g／kg，生理盐水组给予相同体积的生理盐水。PTSD动物模型建立采用单一持续性刺激（SPS）方式，通过僵立反应和高架十字迷宫分别测试SPS24h、7d的恐惧记忆及焦虑行为，在SPS7d检测训练后CPP值，并用免疫组织化学方法测定大鼠杏仁核区域多巴胺D1受体的表达。结果与正常对照组比较，仅在SPS7d时PTSD组大鼠僵立时间显著延长[（89．13±8．60）S，（22．25±5．85）S，q=8．77，P〈0．01]；以及进入开放臂次数、时间明显降低[（4．25±1．26）次，（14.38±2.18）次，（12．38＋-3．30）S，（40．38±7．29）S，q分别为4．74和4．08，均P〈0．01]；CPP测试中PE组训练后CPP值明显高于训练前，差异有统计学意义（q=31．81，P〈0．01），其余CE、PS及CS组训练前后CPP值均差异无统计学意义（q分别为1．53，0．01，0．27，P〉0．05）；PE组训练后的CPP值明显高于CS组、CE组和PS组（q分别为-38．32，-22．21，-33．38，P〈0．05）。SPS7d4组大鼠杏仁核区域多巴胺D1受体阳性细胞数免疫组化评分差异无统计学意义（F=0．07，P〉0．05）。结论PTSD样大鼠易于形成酒精条件性位置偏爱，可能与杏仁核多巴胺D1受体数量变化无关。
文摘AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,and the high myopia was diagnosed by optometry,the diopter was less than-6.00 D,and CNV was induced by 532 nm laser.The changes of dopamine D1 receptor(DRD1),dopamine D2 receptor(DRD2),and vascular endothelial growth factor A(VEGFA)were detected by Western blot technology at 0.5,1,2h,and 7d after 0.01%,0.05%,and 0.1%atropine eye drops,respectively,the area of CNV was measured.RESULTS:Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group,and the higher the concentration,the more significant the inhibitory effect(P<0.05).CONCLUSION:The 0.01%,0.05%,0.1%atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1,and the effect of 0.05%and 0.1%atropine eye drops is more significant.
基金Beijing Municipal Natural Science Foundation(Grant No.7192100)Innovation Team of Ministry of Education(Grant No.BMU2017TD003)
文摘Breast cancer is the most common cancer in females with extremely high lethality mainly due to the occurrence of metastasis,which is closely related to cancer stem-like cells(CSCs).It has been reported that CSC frequency in drug-resistant breast cancer and non-small cell lung cancer is reduced by activating dopamine D1 receptor(D1 DR).In the present study,we aimed to investigate the effect of a compound C17 that can be used orally for breast cancer metastasis as well as the underlying mechanism involving the activation of D1 DR.The confocal immunofluorescence analysis demonstrated that D1 DR was up-regulated by C17.The cell survival and colony formation were inhibited by C17 through the detection by Sulforhodamine B colorimetric(SRB)assay and colony formation assay,respectively.Results from both wound healing assay and transwell assay demonstrated that C17 inhibited the migration of 4T1 cells.Flow cytometry analysis indicated that C17 significantly reduced the CSC frequency.In addition,C17 could inhibit the lung metastasis in 4T1 orthotopic mouse model of breast cancer without obvious toxicity,and it could up-regulate the expression of intratumoral E-cadherin and down-regulate the expressions of Snail and N-cadherin in primary breast tumor,which might be related to the activation of D1 DR.Our findings provided a potential candidate compound for the treatment of metastatic breast cancer with good compliance and safety.
