基于P2X2、M3和β3-AR受体探讨五苓散改善骶髓损伤后神经源性膀胱尿潴留的作用机制OA
Mechanism of Wuling Powder in Improving Neurogenic Bladder Urinary Retention in Rats After Sacral Spinal Cord Injury Based on P2X2,M3,and β3-AR Receptors
目的:探讨五苓散对骶髓损伤后神经源性膀胱(neurogenic bladder,NB)大鼠模型尿潴留的改善作用及其潜在机制.方法:采用 Hassan Shaker 脊髓横断术建立膀胱逼尿肌无反射型 NB 大鼠模型,将大鼠分为假手术组,模型组,五苓散低、中、高剂量(1.5、3、6g·kg-1)组,每组10 只.连续灌胃20 d 后,采用 HE 染色观察大鼠膀胱组织病理形态,qPCR 与 Western blot 检测大鼠膀胱组织嘌呤受体亚型 2(purinergic receptor subtype 2,P2X2)、β 肾上腺素受体亚型 3(β-adrenergic receptor subtype 3,β3-AR)及毒蕈碱型受体亚型3(muscarinic receptor subtype 3,M3-R)的mRNA 与蛋白表达水平,ELISA 检测血清多巴胺(do-pamine,DA)含量,比色法检测血清三磷酸腺苷(adenosine triphosphate,ATP)含量.结果:与假手术组比较,模型组大鼠 BBB 评分显著降低(P<0.01);膀胱组织 HE 染色显示模型组结缔组织排列疏松,伴炎症细胞浸润;膀胱组织 β3-AR mRNA 与蛋白表达水平显著升高,M3-R mRNA 与蛋白表达水平显著降低,P2X2 蛋白表达水平显著升高(P<0.01);血清 DA 与 ATP 含量均显著降低(P<0.05).与模型组比较,五苓散中、高剂量组大鼠 BBB 评分显著升高(P<0.01),膀胱组织病理异常程度减轻;膀胱组织 β3-AR mRNA 与蛋白表达水平显著降低,M3-R mRNA 与蛋白表达水平显著升高,P2X2 蛋白表达水平显著降低(P<0.05);血清 DA 与 ATP 含量均显著升高(P<0.05).结论:五苓散可能通过调控 P2X2、M3-R 和 β3-AR 的表达,促进神经功能和能量代谢的恢复,从而有效改善脊髓损伤后大鼠的尿潴留症状.
Objective:To investigate the effect of Wuling Powder on the improvement of urinary retention in a rat model of neurogenic bladder(NB)after sacral spinal cord injury and its potential mechanism.Methods:A bladders with detrusor areflexia NB rat model was established by Hassan Shaker spinal cord transection.Rats were divided into a sham operation group,model group,and low,medium,and high dose Wuling Powder groups(1.5,3,6 g·kg-1),with 10 rats in each group.After 20 consecutive days of intragastric adminis-tration,HE staining was used to observe the pathological morphology of rat bladder tissue.qPCR and Western blot were used to detect the mRNA and protein expression levels of purinergic receptor subtype 2(P2X2),β-adrenergic receptor subtype 3(β3-AR),and muscarinic receptor subtype 3(M3-R)in rat bladder tissue.ELISA was used to detect serum dopamine(DA)levels,and a colorimet-ric method was used to detect adenosine triphosphate(ATP)levels in serum.Results:Compared with the sham surgery group,the BBB scores of rats in the model group were significantly decreased(P<0.01);hematoxylin and eosin(HE)staining of bladder tissue showed loose arrangement of connective tissue with inflammatory cell infiltration in the model group;bladder tissue β3-AR mRNA and protein expression levels were significantly increased,M3-R mRNA and protein expression levels were significantly decreased,and P2X2 protein expression levels were significantly increased(P<0.01);serum DA and ATP content were both significantly decreased(P<0.05).Compared with the model group,the BBB scores of rats in the middle-and high-dose groups of Wuling Powder were significantly increased(P<0.05),and the pathological abnormalities in the bladder tissue were alleviated;bladder tissue β3-AR mRNA and protein expression levels were significantly decreased,M3-R mRNA and protein expression levels were significantly in-creased,and P2X2 protein expression levels were significantly decreased(P<0.05);serum DA and ATP content were both significantly increased(P<0.05).Conclusion:Wuling Powder may improve urinary retention symptoms in rats after spinal cord injury by regulating the expression of P2X2,M3-R,and β3-AR,promoting the recovery of neural function and energy metabolism.
赵树克;肖小乔;赵照禾;林圳;王杨;张琳;王振亮
河南中医药大学中医学院(仲景学院),河南 郑州 450046河南中医药大学中医学院(仲景学院),河南 郑州 450046河南中医药大学中医学院(仲景学院),河南 郑州 450046河南中医药大学中医学院(仲景学院),河南 郑州 450046河南中医药大学中医学院(仲景学院),河南 郑州 450046河南中医药大学中医学院(仲景学院),河南 郑州 450046河南中医药大学中医学院(仲景学院),河南 郑州 450046
医药卫生
五苓散神经源性膀胱尿潴留P2X2M3-Rβ3-AR骶髓损伤
Wuling Powderneurogenic bladderurinary retentionP2X2M3-Rβ3-ARsacral spinal cord injury
《中医学报》 2026 (6)
1309-1314,6
河南省重点研发专项项目(231111310300)河南省郑州市协同创新专项项目(2023XTCX049)
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