BNP/NPR-A/BKCa信号通路在大鼠神经痛形成中的作用及机制研究  

The Role and Mechanism of BNP/NPR-A/BKCa Signaling Pathway in Neuralgia Formation in Rats

作　　者：薛继娇 冯慧 孟祥君 李帅[1] 席富强 XUE Ji-jiao;FENG Hui;MENG Xiang-jun;LI Shuai;XI Fu-qiang(Department of Neurology,The First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou,Inner Mongolia,830011,China)

机构地区：[1]内蒙古科技大学包头医学院第一附属医院神经内科,内蒙古包头830011

出　　处：《现代生物医学进展》2023年第15期2817-2821,2867,共6页Progress in Modern Biomedicine

基　　金：内蒙古自治区教育厅学校科学研究项目(NJZY22085)。

摘　　要：目的:探讨BNP/NPR-A/BKCa信号通路在大鼠神经痛形成中的作用及机制研究。方法:选取SPF级大鼠作为研究对象,并构建神经痛病理性疼痛大鼠模型。并分为空白对照组、假手术组、A组(20ng/mLBNP梢内注射)、B组(50ng/mLBNP梢内注射)和C组(100ng/mLBNP梢内注射)。采用qRT-PCR和Westernblot检测NPR-A和BKCa的mRNA和蛋白表达水平。采用ELISA法检查炎症因子。全细胞膜片钳技术检测痛觉神经元BKCa通道电流;对大鼠进行机械性痛觉过敏测试和温度性痛觉敏感测试。结果:与空白组相比,模型组、A、B和C组PWT和PWL明显更低(P<0.05);与模型组相比,A、B和C组PWT和PWL明显更高,且C组大于B和A组,B组大于A组(P<0.05)。与空白组相比,模型组NPR-A的蛋白和mRAN水平明显更高,而BKCa-α明显更低(P<0.05);与模型组相比,A、B和C组NPR-A和BKCa-α的蛋白和mRNA明显更高,且C组大于B和A组,B组大于A组(P<0.05)。各电压水平,与空白组相比,模型组、A、B和C组BKCa-α电流水平明显更低(P<0.05);与模型组相比,A、B和C组BKCa-α电流水平明显更高,且C组大于B和A组,B组大于A组(P<0.05)。与空白组相比,模型组、A、B和C组TNF-α、IL-6和IL-18水平明显更高(P<0.05);与模型组相比,A、B和C组TNF-α、IL-6和IL-18水平明显更低,且C组小于B和A组,B组小于A组(P<0.05)。结论:靶向上调BNP的表达水平可增加BKCa的表达及BKCa电流,同时BNP的表达上调还有助于抑制炎症因子水平,从而达到多途径缓解疼痛的目的。Objective:To investigate the role and mechanism of BNP/NPR-A/BKCa signaling pathway in neuralgia formation in rats.Methods:SPF rats were selected as research subjects and pathologic pain rat model of neuralgia was established.They were divided into blank control group,sham operation group,group A(20 ng/mL BNP injection),group B(50 ng/mL BNP injection)and group C(10Ong/ml BNP injection).The mRNA and protein expression levels of NPR-A and BKCa were detected by qRT-PCR and Western blot.Inflammatory factors were examined by ELISA.BKCa channel currents of pain-sensing neurons were detected by whole-cell patch clamp technique.Mechanical hyperalgesia and temperature hyperalgesia were tested in rats.Results:Compared with blank group,PWT and PWL in model group,groups A,B and C were lower(P<0.05).Compared with the model group,the PWT and PWL in groups A,B and C were higher,and the PWT and PWL in group C were higher than those in groups B and A,and the PWL in group B was higher than that in group A(P<0.05).Compared with blank group,the level of NPR-A protein and mRAN was higher in model group,while the level of BKCa-αwas lower(P<0.05).Compared with model group,the protein and mRNA of NPR-A and BKCa-αin groups A,B and C were higher,and group C was higher than that in groups B and A,and group B was higher than that in group A(P<0.05).Compared with blank group,the current level of BKCa-αin model group,groups A,B and C was lower(P<0.05).Compared with the model group,the current level of BKCa-αin groups A,B and C was significantly higher,and group C was higher than that in groups B and A,and group B was higher than that in group A(P<0.05).Compared with blank group,the levels of TNF-α,IL-6 and IL-18 in model group,groups A,B and C were significantly higher(P<0.05).Compared with model group,the levels of TNF-α,IL-6 and IL-18 in groups A,B and C were significantly lower,and group C was lower than that in groups B and A,and group B was lower than that in group A(P<0.05).Conclusion:Targeted up-regulation of BNP expression level

关 键 词：BNP/NPR-A/BKCa信号通路 大鼠 神经痛 

分 类 号：R-33[医药卫生] R338.3[生物学—生物化学] Q593.2