机械敏感通道Piezo 1和Piezo 2促进幼鼠神经源性膀胱纤维化的初步研究  

A preliminary study of mechanosensitive channels Piezo 1 and Piezo 2 promoting neurogenic bladder fibrosis in young rats

作　　者：吕磊 张艳平 李琦[2] 王俊魁[3] 杨帅 周钊凯 李帅[1] 文一博[1] 刘亚凯 司国威 刘星辰 文建国[1] LYU Lei;ZHANG Yanping;LI Qi;WANG Junkui;YANG Shuai;ZHOU Zhaokai;LI Shuai;WEN Yibo;LIU Yakai;SI Guowei;LIU Xingchen;WEN Jianguo(Department of Urology,Henan Joint International Paediatric Urodynamic Laboratory,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052;Department of Pediatric Surgery,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052;Department of Ultrasound,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052;Department of Urology,The First Affiliated Hospital of Xinxiang Medical College,Xinxiang 453000;Department of Gynecology,Xinyang Central Hospital,Xinyang 464000,China)

机构地区：[1]郑州大学第一附属医院泌尿外科,河南省小儿尿动力国际联合实验室,河南郑州450052 [2]郑州大学第一附属医院小儿外科,河南郑州450052 [3]郑州大学第一附属医院超声科,河南郑州450052 [4]新乡医学院第一附属医院泌尿外科,河南新乡453000 [5]信阳市中心医院妇科,河南信阳464000

出　　处：《现代泌尿外科杂志》2025年第4期343-349,363,共8页Journal of Modern Urology

基　　金：国家自然科学基金项目(No.U1904208,No.82470807)。

摘　　要：目的探究机械敏感通道Piezos(Piezo 1和Piezo 2)在神经源性膀胱(NB)幼鼠中的变化及其对膀胱纤维化的作用,为临床寻找治疗NB的新靶点提供参考。方法将30只雌性幼年SD大鼠按随机数表法分为5组:假手术组(Sham组)、神经离断2周组(NB-2W组)、神经离断6周组(NB-6W组)、神经离断+Piezos抑制剂2周组(NB-P-2W组)和神经离断+Piezos抑制剂6周组(NB-P-6W组),每组6只。通过离断幼鼠L6及S1脊神经构建NB动物模型,神经离断组造模后不进行干预,神经离断+Piezos抑制剂组则在造模后每2天腹腔注射Piezos抑制剂GsMTx4(10 mg/kg)。在离断后2周和6周进行幼鼠膀胱测压和超声检查,并取膀胱组织检测Piezos及纤维化相关指标Ⅰ型胶原蛋白(CollagenⅠ)及α-平滑肌肌动蛋白(α-SMA)的相对表达水平。结果膀胱测压显示,NB-2W组幼鼠基础膀胱压力明显升高,NB-6W组略有下降但仍高于Sham组(P<0.05)。NB-P-2W组的基础膀胱压力低于NB-2W组但较Sham组高,NB-P-6W组的基础膀胱压力低于NB-6W组但高于Sham组(P<0.05)。与Sham组比较,NB-2W组和NB-6W组最大膀胱测压容量(MCC)出现先升高后下降趋势(P<0.05)。与NB-2W组比较,NB-P-2W组的漏尿点压(BLPP)更低,MCC和膀胱顺应性(BC)更高(P<0.05);与NB-6W组比较,NB-P-6W组的BLPP更低,MCC和BC更高(P<0.05)。HE、MASSON染色及超声结果显示,随着神经离断时间延长,膀胱纤维化逐渐加重,膀胱壁粗糙增厚,内可见结石,肾脏逐渐出现肾盂扩张积水,而NB-P-2W组和NB-P-6W组纤维化程度轻于NB-2W组和NB-6W组,未见上尿路扩张积水。此外,Weston blot及免疫组化结果显示NB-2W组和NB-6W组的Piezos、CollagenⅠ及α-SMA的相对表达水平明显高于Sham组(P<0.01);NB-P-2W组和NB-P-6W组的Piezos、CollagenⅠ及α-SMA的相对表达水平则分别低于NB-2W组和NB-6W组(P<0.01)。结论机械敏感通道Piezos在NB幼鼠中表达升高,可能参与膀胱纤维化进展,但其机制有待进一步研究。Objective To explore the changes of mechanosensitive channels Piezos(Piezo 1 and Piezo 2)in neurogenic bladder(NB)of young rats and their effects,so as to provide reference for clinical search of new therapeutic targets.Methods A total of 30 female young SD rats were divided into 5 groups based on random number table method:sham operation group(sham),2-week nerve transection group(NB-2W),6-week nerve transection group(NB-6W),2-week nerve transection+Piezos inhibitor group(NB-P-2W)and 6-week nerve transection+Piezos inhibitor group(NB-P-6W),with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling,while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4(10 mg/kg)every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes(CollagenⅠandα-smooth muscle actin)were detected in bladder tissues.Results The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased,while it was slightly decreased but was still higher in NB-6W group than in the sham group(P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group,but was higher than that in the sham group;basal bladder pressure was lower in NB-P-6W group than in NB-6W group,but higher than that in the sham group(P<0.05).Compared with the sham group,the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity(MCC)(P<0.05).Compared with NB-2W group,NB-P-2W group had lower bladder leakage point pressure(BLPP),but higher MCC and bladder compliance(BC)(P<0.05).Compared with NB-6W group,NB-P-6W group had significantly lower BLPP but higher MCC and BC(P<0.05).HE and MASSON staining and ultrasound results showed that,with the extension of nerve transection time,bladder fibrosis gradually worsened,the bladder wal

关 键 词：Piezo 1 Piezo 2 神经源性膀胱 膀胱纤维化 幼鼠 机械敏感通道 

分 类 号：R694[医药卫生—泌尿科学]