葛根素调控SDF-1/CXCR4通路改善压力性尿失禁大鼠排尿功能的研究OA
Research of puerarin improving the urination function of rats with stress urinary incontinence by adjusting the SDF-1/CXCR4 pathway
目的 探究葛根素(PU)调控基质细胞衍生因子-1(SDF-1)/CXC趋化因子受体4(CXCR4)通路对压力性尿失禁(SUI)大鼠排尿功能的影响及作用机制.方法 采用双侧卵巢切除联合阴道扩张构建SUI大鼠模型.建模后的大鼠随机分为模型组、低剂量实验组、高剂量实验组、阳性对照组、激活剂组、抑制剂组,每组10只;另外选取等量10只正常大鼠为空白对照组.其中低剂量实验组、高剂量实验组大鼠灌胃给予17.5、70.0 mg·kg-1 PU;阳性对照组大鼠灌胃给予20.0 mg·kg-1盐酸米多君;激活剂组尾静脉注射10.0 mg·kg-1通路激活剂CTCE-0214;抑制剂组大鼠灌胃给予70.0 mg·kg-1 PU和腹腔注射5.0 mg·kg-1通路抑制剂AMD3100.用机械刺激法检测大鼠喷嚏阳性率,用膀胱灌注测压法尿动力学相关指标[最大膀胱容量(MBC)、腹部漏尿点压力(ALPP)和漏尿点压力(LPP)],用电生理法检测大鼠盆底肌肉收缩力/肌重比值和排尿功能相关指标(排尿量、残余尿量及排尿效率),用苏木精-伊红(HE)和Masson染色检测大鼠尿道组织病理变化,用蛋白免疫印迹法检测大鼠尿道组织中SDF-1/CXCR4通路相关蛋白表达.结果 空白对照组、模型组、低、高剂量实验组、阳性对照组、激活剂组和抑制剂组大鼠尿动力学MBC指标分别为(6.57±0.81)、(1.36±0.17)、(1.95±0.24)、(5.83±0.62)、(5.64±0.58)、(5.72±0.60)和(2.49±0.35)mL;ALPP 指标分别为(45.76±4.83)、(11.52±1.49)、(17.68±1.95)、(41.25±4.37)、(39.06±4.16)、(40.65±4.23)和(18.97±2.44)mmHg;LPP 指标标分别为(43.29±5.08)、(9.76±1.35)、(14.58±1.63)、(39.62±4.59)、(37.05±3.92)、(38.26±4.25)和(18.43±2.16)mmHg;盆底肌肉收缩力/肌重比值分别为4.03±0.42、1.06±0.15、1.79±0.18、3.85±0.43、3.62±0.37、3.73±0.39 和1.94±0.21;排尿效率分别为(96.24±3.76)％、(41.65±5.83)％、(58.39±6.45)％、(89.46±8.26)％、(85.12±9.04)％、(87.14±8.59)％和(64.95±6.72)％;SDF-1 蛋白相对表达水平分别为 0.99±0.12、0.42±0.06、0.58±0.08、0.91±0.09、0.86±0.09、0.88±0.09 和 0.63±0.07;CXCR4 蛋白相对表达水平分别为 1.02±0.11、0.37±0.04、0.46±0.06、0.93±0.12、0.89±0.11、0.91±0.12和0.49±0.05;磷酸化蛋白激酶B/蛋白激酶B(p-AKT/AKT)分别为 0.90±0.09、0.28±0.03、0.52±0.06、0.86±0.09、0.81±0.07、0.83±0.08和0.43±0.05;空白对照组的上述指标与模型组比较,模型组与高剂量实验组比较,高剂量实验组与抑制剂组比较,在统计学上差异均有统计学意义(均P＜0.05).结论 PU能够改善SUI大鼠排尿功能,可能与激活SDF-1/CXCR4通路相关.
Objective To investigate the effect of puerarin(PU)on the urination function of rats with stress urinary incontinence(SUI)by adjusting the stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)pathway and to explore its mechanism of action.Methods A rat model of SUI was established by bilateral oophorectomy combined with vaginal dilation.After successful modeling,the rats were randomly divided into the model group,low dose-experimental group,high dose-experimental group,the positive control group,the activator group and the inhibitor group,10 rats in each group.Additionally,10 normal rats were selected as the blank control group.Rats in the low and high dose-experimental groups were administered 17.5 and 70.0 mg·kg-1 PU by gavage,respectively.Rats in the positive control group were administered 20.0 mg·kg-1 midodrine by gavage.Rats in the activator group were injected with 10.0 mg·kg-1 pathway activator CTCE-0214 via the tail vein.Rats in the inhibitor group were administered 70.0 mg·kg-1 PU by gavage combined with intraperitoneal injection of 5.0 mg·kg-1 pathway inhibitor AMD3100.The sneezing positive rate was evaluated by mechanical stimulation method,urodynamic indicators[maximum bladder capacity(MBC),abdominal leak point pressure(ALPP)and leak point pressure(LPP)]were determined by cystometrography,pelvic floor muscle contractility/muscle weight ratio and urination function indicators(urine output,residual urine volume and voiding efficiency)were evaluated by electrophysiological method,pathological changes of urethral tissue by hematoxylin-eosin(HE)and Masson staining,and the relative expression levels of SDF-1/CXCR4 pathway-related proteins in urethral tissue were determined by Western blotting.Results The urodynamic indicator MBC in the blank control group,model group,low dose-experimental group,high dose-experimental group,the positive control group,the activator group and the inhibitor group were(6.57±0.81),(1.36±0.17),(1.95±0.24),(5.83±0.62),(5.64±0.58),(5.72±0.60)and(2.49±0.35)mL,respectively;the ALPP was(45.76±4.83),(11.52±1.49),(17.68±1.95),(41.25±4.37),(39.06±4.16),(40.65±4.23)and(18.97±2.44)mmHg,respectively;the LPP was(43.29±5.08),(9.76±1.35),(14.58±1.63),(39.62±4.59),(37.05±3.92),(38.26±4.25)and(18.43±2.16)mmHg,respectively;the pelvic floor muscle contractility/muscle weight ratio was 4.03±0.42,1.06±0.15,1.79±0.18,3.85±0.43,3.62±0.37,3.73±0.39 and 1.94±0.21,respectively;the voiding efficiency was(96.24±3.76)％,(41.65±5.83)％,(58.39±6.45)％,(89.46±8.26)％,(85.12±9.04)％,(87.14±8.59)％and(64.95±6.72)％,respectively;the relative expression levels of SDF-1 protein was 0.99±0.12,0.42±0.06,0.58±0.08,0.91±0.09,0.86±0.09,0.88±0.09 and 0.63±0.07,respectively;the relative expression levels of CXCR4 protein was 1.02±0.11,0.37±0.04,0.46±0.06,0.93±0.12,0.89±0.11,0.91±0.12 and 0.49±0.05,respectively;the phosphorylated protein kinase B/protein kinase B(p-AKT/AKT)ratio was 0.90±0.09,0.28±0.03,0.52±0.06,0.86±0.09,0.81±0.07,0.83±0.08 and 0.43±0.05,respectively.Comparisons between the blank control group and the model group,between the model group and the low dose-,high dose-experimental group,positive group or activator group,and between the high dose-experimental group and the inhibitor group all showed statistically significant differences(all P＜0.05).Conclusion PU can improve the urination function of rats with SUI,and this may be related to the activation of the SDF-1/CXCR4 pathway.
陈嫣;杨晨;叶利群
宁波市中医院/浙江中医药大学附属宁波市中医院妇二科,浙江宁波 315010||浙江中医药大学宁波临床医学院,浙江宁波 315010宁波市中医院/浙江中医药大学附属宁波市中医院妇二科,浙江宁波 315010||浙江中医药大学宁波临床医学院,浙江宁波 315010宁波市中医院/浙江中医药大学附属宁波市中医院妇二科,浙江宁波 315010||浙江中医药大学宁波临床医学院,浙江宁波 315010
医药卫生
葛根素压力性尿失禁基质细胞衍生因子-1/CXC趋化因子受体4通路排尿功能
puerarinstress urinary incontinencematrix cell-derived factor-1/cxc chemokine receptor 4 pathwayurination function
《中国临床药理学杂志》 2026 (12)
1703-1709,7
国家中医药管理局科技司——浙江省中医药管理局共建项目(编号:GZY-ZJ-KJ-Z3090)
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