目的通过研究匹罗卡品致癫痫大鼠海马组织中P2X2受体(嘌呤受体)的表达变化,探讨其在颞叶癫痫发病中的作用机制。方法应用氯化锂-匹罗卡品腹腔注射建立大鼠颞叶癫痫模型,并予以P2X2受体拮抗剂亮蓝G(Brilliant Blue G,BBG)腹腔注射,应用We...目的通过研究匹罗卡品致癫痫大鼠海马组织中P2X2受体(嘌呤受体)的表达变化,探讨其在颞叶癫痫发病中的作用机制。方法应用氯化锂-匹罗卡品腹腔注射建立大鼠颞叶癫痫模型,并予以P2X2受体拮抗剂亮蓝G(Brilliant Blue G,BBG)腹腔注射,应用Western blot及Real-time PCR技术检测大鼠海马组织P2X2受体的表达,免疫组化技术检测各组大鼠海马组织中谷氨酸(glutamate,GLU)表达水平。结果 Western blot及Real-time PCR结果显示:慢性自发性癫痫发作组中P2X2表达明显增高(P<0.05),BBG干预组表达减低P<0.05)。免疫组化检测显示:GLU在BBG干预组较慢性自发性发作组中释放减少(P<0.05),且与BBG剂量呈负相关性。结论 P2X2受体通路可能参与颞叶癫痫的发病过程,并有望成为新一代治疗颞叶癫痫的药物靶点。展开更多
AIM:To investigate the colocalization,density and profile of neuronal areas of enteric neurons in the ileum of male obese mice.METHODS:The small intestinal samples of male mice in an obese group(OG)(C57BL/6J ob/ob)and...AIM:To investigate the colocalization,density and profile of neuronal areas of enteric neurons in the ileum of male obese mice.METHODS:The small intestinal samples of male mice in an obese group(OG)(C57BL/6J ob/ob)and a control group(CG)(+/+)were used.The tissues were analyzed using a double immunostaining technique for immunoreactivity(ir)of the P2X2 receptor,nitric oxide synthase(NOS),choline acetyl transferase(ChAT)and calretinin(Calr).Also,we investigated the density and profile of neuronal areas of the NOS-,ChAT-and Calrir neurons in the myenteric plexus.Myenteric neurons were labeled using an NADH-diaphorase histochemical staining method.RESULTS:The analysis demonstrated that the P2X2receptor was expressed in the cytoplasm and in the nuclear and cytoplasmic membranes only in the CG.Neuronal density values(neuron/cm2)decreased 31%(CG:6579±837;OG:4556±407)and 16.5%(CG:7796±528;OG:6513±610)in the NOS-ir and calretininir neurons in the OG,respectively(P<0.05).Density of ChAT-ir(CG:6200±310;OG:8125±749)neurons significantly increased 31%in the OG(P<0.05).Neuron size studies demonstrated that NOS,ChAT,and Calr-ir neurons did not differ significantly between the CG and OG groups.The examination of NADH-diaphorase-positive myenteric neurons revealed an overall similarity between the OG and CG.CONCLUSION:Obesity may exert its effects by promoting a decrease in P2X2 receptor expression and modifications in the density of the NOS-ir,ChAT-ir and CalR-ir myenteric neurons.展开更多
目的通过研究P2X2受体(嘌呤受体)蛋白在颞叶癫痫大鼠脑组织中的表达水平及星形胶质细胞的增殖水平,以及应用P2X2受体拮抗剂亮蓝G(Brilliant Blue G,BBG)后对颞叶癫痫的影响,探讨P2X2受体在颞叶癫痫发病机制中的作用。方法应用氯化锂-匹...目的通过研究P2X2受体(嘌呤受体)蛋白在颞叶癫痫大鼠脑组织中的表达水平及星形胶质细胞的增殖水平,以及应用P2X2受体拮抗剂亮蓝G(Brilliant Blue G,BBG)后对颞叶癫痫的影响,探讨P2X2受体在颞叶癫痫发病机制中的作用。方法应用氯化锂-匹罗卡品腹腔注射建立SD大鼠颞叶癫痫模型,将大鼠分为正常盐水对照组、急性发作组、慢性自发性发作组;其中慢性自发性发作组又分为空白对照组(生理盐水)和亮蓝G干预组,应用免疫组化检测各组大鼠海马区P2X2受体及胶质纤维酸性蛋白(GFAP)的表达水平,GFAP反映星形胶质细胞的增殖水平。结果免疫组化检测发现,P2X2受体主要表达于大鼠海马组织的CA1、CA3、齿状回、门区,并且在丘脑也有一定的表达;P2X2受体及GFAP在慢性自发性发作空白对照组中的表达明显高于正常盐水对照组和急性发作组(P<0.05);而亮蓝G干预组与慢性自发性发作空白对照组相比,P2X2受体及GFAP表达水平明显降低(P<0.05)。结论 P2X2受体可能在颞叶癫痫的发病机制中有重要作用,阻滞P2X2受体可能是治疗颞叶癫痫的潜在靶点。展开更多
Pain is unfortunately a quite common symptom for cancer patients. Normally pain starts as an episodic experience at early cancer phases to become chronic in later stages. In order to improve the quality of life of onc...Pain is unfortunately a quite common symptom for cancer patients. Normally pain starts as an episodic experience at early cancer phases to become chronic in later stages. In order to improve the quality of life of oncological patients, anti-cancer treatments are often accompanied by analgesic therapies. The P2 X receptor are adenosine triphosphate(ATP) gated ion channels expressed by several cells including neurons, cancer and immune cells. Purinergic signaling through P2 X receptors recently emerged as possible common pathway for cancer onset/growth and pain sensitivity. Indeed, tumor microenvironment is rich in extracellular ATP, which has a role in both tumor development and pain sensation. The study of the different mechanisms by which P2 X receptors favor cancer progression and relative pain, represents an interesting challenge to design integrated therapeutic strategies for oncological patients. This review summarizes recent findings linking P2 X receptors and ATP to cancer growth, progression and related pain. Special attention has been paid to the role of P2X2, P2X3, P2X4 and P2X7 in the genesisof cancer pain and to the function of P2X7 in tumor growth and metastasis. Therapeutic implications of the administration of different P2 X receptor blockers to alleviate cancer-associated pain sensations contemporarily reducing tumor progression are also discussed.展开更多
文摘目的通过研究匹罗卡品致癫痫大鼠海马组织中P2X2受体(嘌呤受体)的表达变化,探讨其在颞叶癫痫发病中的作用机制。方法应用氯化锂-匹罗卡品腹腔注射建立大鼠颞叶癫痫模型,并予以P2X2受体拮抗剂亮蓝G(Brilliant Blue G,BBG)腹腔注射,应用Western blot及Real-time PCR技术检测大鼠海马组织P2X2受体的表达,免疫组化技术检测各组大鼠海马组织中谷氨酸(glutamate,GLU)表达水平。结果 Western blot及Real-time PCR结果显示:慢性自发性癫痫发作组中P2X2表达明显增高(P<0.05),BBG干预组表达减低P<0.05)。免疫组化检测显示:GLU在BBG干预组较慢性自发性发作组中释放减少(P<0.05),且与BBG剂量呈负相关性。结论 P2X2受体通路可能参与颞叶癫痫的发病过程,并有望成为新一代治疗颞叶癫痫的药物靶点。
基金Supported by Sao Paulo Research Foundation(FAPESP/Sao Paulo Research Foundation/Proc:05/04752-0)and CAPES Fellowship
文摘AIM:To investigate the colocalization,density and profile of neuronal areas of enteric neurons in the ileum of male obese mice.METHODS:The small intestinal samples of male mice in an obese group(OG)(C57BL/6J ob/ob)and a control group(CG)(+/+)were used.The tissues were analyzed using a double immunostaining technique for immunoreactivity(ir)of the P2X2 receptor,nitric oxide synthase(NOS),choline acetyl transferase(ChAT)and calretinin(Calr).Also,we investigated the density and profile of neuronal areas of the NOS-,ChAT-and Calrir neurons in the myenteric plexus.Myenteric neurons were labeled using an NADH-diaphorase histochemical staining method.RESULTS:The analysis demonstrated that the P2X2receptor was expressed in the cytoplasm and in the nuclear and cytoplasmic membranes only in the CG.Neuronal density values(neuron/cm2)decreased 31%(CG:6579±837;OG:4556±407)and 16.5%(CG:7796±528;OG:6513±610)in the NOS-ir and calretininir neurons in the OG,respectively(P<0.05).Density of ChAT-ir(CG:6200±310;OG:8125±749)neurons significantly increased 31%in the OG(P<0.05).Neuron size studies demonstrated that NOS,ChAT,and Calr-ir neurons did not differ significantly between the CG and OG groups.The examination of NADH-diaphorase-positive myenteric neurons revealed an overall similarity between the OG and CG.CONCLUSION:Obesity may exert its effects by promoting a decrease in P2X2 receptor expression and modifications in the density of the NOS-ir,ChAT-ir and CalR-ir myenteric neurons.
文摘目的通过研究P2X2受体(嘌呤受体)蛋白在颞叶癫痫大鼠脑组织中的表达水平及星形胶质细胞的增殖水平,以及应用P2X2受体拮抗剂亮蓝G(Brilliant Blue G,BBG)后对颞叶癫痫的影响,探讨P2X2受体在颞叶癫痫发病机制中的作用。方法应用氯化锂-匹罗卡品腹腔注射建立SD大鼠颞叶癫痫模型,将大鼠分为正常盐水对照组、急性发作组、慢性自发性发作组;其中慢性自发性发作组又分为空白对照组(生理盐水)和亮蓝G干预组,应用免疫组化检测各组大鼠海马区P2X2受体及胶质纤维酸性蛋白(GFAP)的表达水平,GFAP反映星形胶质细胞的增殖水平。结果免疫组化检测发现,P2X2受体主要表达于大鼠海马组织的CA1、CA3、齿状回、门区,并且在丘脑也有一定的表达;P2X2受体及GFAP在慢性自发性发作空白对照组中的表达明显高于正常盐水对照组和急性发作组(P<0.05);而亮蓝G干预组与慢性自发性发作空白对照组相比,P2X2受体及GFAP表达水平明显降低(P<0.05)。结论 P2X2受体可能在颞叶癫痫的发病机制中有重要作用,阻滞P2X2受体可能是治疗颞叶癫痫的潜在靶点。
基金Supported by Grants to Elena Adinolfi from the Italian association for Cancer research(MFAG11630)from the Region Emilia Romagna(Young researchers funds,Bando Alessandro Liberati)
文摘Pain is unfortunately a quite common symptom for cancer patients. Normally pain starts as an episodic experience at early cancer phases to become chronic in later stages. In order to improve the quality of life of oncological patients, anti-cancer treatments are often accompanied by analgesic therapies. The P2 X receptor are adenosine triphosphate(ATP) gated ion channels expressed by several cells including neurons, cancer and immune cells. Purinergic signaling through P2 X receptors recently emerged as possible common pathway for cancer onset/growth and pain sensitivity. Indeed, tumor microenvironment is rich in extracellular ATP, which has a role in both tumor development and pain sensation. The study of the different mechanisms by which P2 X receptors favor cancer progression and relative pain, represents an interesting challenge to design integrated therapeutic strategies for oncological patients. This review summarizes recent findings linking P2 X receptors and ATP to cancer growth, progression and related pain. Special attention has been paid to the role of P2X2, P2X3, P2X4 and P2X7 in the genesisof cancer pain and to the function of P2X7 in tumor growth and metastasis. Therapeutic implications of the administration of different P2 X receptor blockers to alleviate cancer-associated pain sensations contemporarily reducing tumor progression are also discussed.
