经尿道联合灌注SCL和Cx43基因慢病毒对糖尿病膀胱功能的影响  

Effect of combined transurethral instillation of SCL and Cx43 gene lentivirus on diabetic bladder function

作　　者：轩留明 马路平[1] 欧阳松[1] 孙鹏 谭明辉 张永强 王勤章[1] Xuan Liuming;Ma Luping;Ouyang Song;Sun Peng;Tan Minghui;Zhang Yongqiang;Wang Qinzhang(Dept of Urology Surgery,The First Affiliated Hospital of Medical College,Shihezi University,Shihezi 832000)

机构地区：[1]石河子大学医学院第一附属医院泌尿外科,石河子832000

出　　处：《安徽医科大学学报》2022年第10期1546-1551,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81960147)。

摘　　要：目的探究干细胞白血病基因(SCL)重组慢病毒和缝隙连接蛋白基因(Cx43)重组慢病毒联合作用对豚鼠糖尿病膀胱(DCP)功能的影响。方法90只健康豚鼠适应性喂养1周后,按照200 mg/kg一次性腹腔注射链脲佐菌素(STZ),定期每周监测随机血糖,正常饲养12周后,通过尿流动力学检查筛选出40只符合标准的豚鼠,将其随机分成4组:糖尿病组、SCL组、Cx43组、SCL+Cx43组。糖尿病组经尿道向膀胱内灌注0.2 ml不含基因的空慢病毒,SCL组、Cx43组使用同样方法分别灌注SCL慢病毒和Cx43慢病毒0.2 ml,SCL+Cx43慢病毒组经尿道灌注SCL、Cx43慢病毒各0.2 ml。转染14 d后进行尿流动力学检查,检查后处死豚鼠,并迅速摘取膀胱,进行冰冻膀胱切片及荧光双染。结果与糖尿病组相比,SCL组、Cx43组在尿流动力学检查中差异无统计学意义(P>0.05),SCL+Cx43组尿流动力学检查可见逼尿肌压力、腹压、膀胱压均有改善(P<0.05)。糖尿病组激光共聚焦可见Cajal间质细胞(ICC)的数量减少,梭形结构及细胞突起明显被破坏,出现细胞裂解状态。SCL组、Cx43组可见ICC样细胞的梭形结构和细胞突起有所改善,细胞数量无明显变化。SCL+Cx43组可见ICC样细胞的数量增多,梭形结构及细胞突起有改善,并可形成ICC-二聚体。结论经尿道联合灌注SCL和Cx43基因重组慢病毒可以成功在豚鼠DCP膀胱中转染,可恢复损伤的ICC细胞的数量及结构,并形成ICC二聚体结构,提高糖尿病膀胱逼尿肌压力,改善排尿无力、腹压排尿等特点,为治疗DCP提供了新的方向。Objective To investigate the effect of the combination of stem cell leukemia(SCL)recombinant lentivirus and connexin 43(Cx43)recombinant lentivirus on the function of diabetic cystipathy(DCP)in guinea pigs.Methods AfteR90 healthy guinea pigs were fed normally foR1 week,streptozotocin(STZ)was injected intraperitoneally at 200 mg/kg in a single dose,and random blood glucose was monitored weekly.AfteR12 weeks of normal feeding,40 guinea pigs meeting the criteria were screened by urodynamic examination and randomly divided into 4 groups:diabetic group,SCL group,Cx43 group,and SCL+Cx43 group.In the diabetic group,0.2 ml of empty lentivirus without gene was instilled into the bladdeRthrough the urethra,in the SCL and Cx43 groups,0.2 ml of SCL lentivirus and Cx43 lentivirus were instilled using the same method,in the SCL+Cx43 lentivirus group,0.2 ml of each SCL and Cx43 lentivirus was instilled through the urethra.AfteR14 days of transfection,urodynamic examination was performed,and then the guinea pigs were executed afteRthe examination,and the bladders were quickly removed foRfrozen bladdeRsections and fluorescent double staining.Results There were no differences in urodynamic examinations between the SCL and Cx43 groups compared to the diabetic group(P>0.05).Urodynamic examination in the SCL+Cx43 group showed improvement in detrusoRpressure,abdominal pressure and bladdeRpressure compared to the diabetic group(P<0.05).In laseRconfocal experiments,the numbeRof interstitial cells of Cajal(ICC)was reduced in the diabetic group,and the spindle structure and cell protrusions were obviously destroyed and appeared in a state of cell lysis.In the SCL and Cx43 groups,there was an improvement in the spindle structure and cell protrusion of ICC-like cells,and there was no significant change in the numbeRof cells.In the SCL+Cx43 group,there was an increase in the numbeRof ICC-like cells,a significant improvement in the spindle structure and cell protrusion,and the formation of ICC-dimers.Conclusion Transurethral co-infusion of SC

关 键 词：糖尿病膀胱病变 CAJAL样间质细胞 干细胞白血病基因 CX43基因 

分 类 号：R694.5[医药卫生—泌尿科学]