低强度脉冲超声激活脂肪源性干细胞增效神经源性勃起功能障碍的海绵体内注射治疗  

Low-intensity pulsed ultrasound activates adipose-derived stem cells to enhance intracavernosal injection treatment for neurogenic erectile dysfunction

作　　者：付冲 郭健 朱亮 滕杰 粟磊 梁恩利[1] 杨永姣 陈业刚[1] Fu Chong;Guo Jian;Zhu Liang;Teng Jie;Su Lei;Liang Enli;Yang Yongjiao;Chen Yegang(Department of Urology,Second Hospital of Tianjin Medical University,Tianjin 300211,china)

机构地区：[1]天津医科大学第二医院泌尿外科,天津300211

出　　处：《中华实验外科杂志》2024年第12期2709-2712,共4页Chinese Journal of Experimental Surgery

基　　金：天津市2021年度中西医结合科研课题(2021171)。

摘　　要：目的探索低强度脉冲超声(LIPUS)增效脂肪源性干细胞(ADSC)海绵体内注射(ICI)治疗海绵体神经损伤性勃起功能障碍的效果和分子机制。方法手术建立海绵体神经损伤性勃起功能障碍(CNI-ED)大鼠模型(共25只),分为5组,每组5只:假手术(Sham)组、海绵体神经损伤(CNI)组、ADSC-ICI治疗组、LIPUS治疗组和LIPUS联合ADSC-ICI治疗(LIPUS+ADSC-ICI)组。通过测量海绵体内压(ICP)/平均动脉压(MAP)评估勃起功能,使用5-乙炔基-2’-脱氧尿嘧啶核苷(EdU)标记、蛋白质印迹法(Western blot)、苏木精-伊红(HE)染色和马松染色、细胞存活率分析探索细胞表型和分子机制。两组间比较采用独立样本t检验,多组之间比较采用单因素方差分析。结果LIPUS+ADSC-ICI治疗组的ICP/MAP水平高于CNI组、ADSC-ICI治疗组及LIPUS治疗组(0.79±0.06比0.51±0.02、0.59±0.02、0.36±0.05,F=106.30,P<0.05)。LIPUS+ADSC-ICI治疗组阴茎组织的炎细胞浸润和纤维化低于CNI、ADSC-ICI组及LIPUS治疗组(31.13±2.05比80.70±4.30、70.36±3.83、56.35±3.37,F=472.10,P<0.05)。注射后第1、3、5天,LIPUS+ADSC-ICI治疗组ADSC滞留高于ADSC组(6.49±0.78比3.43±0.61;5.04±0.69比2.04±0.46;4.09±0.54比1.36±0.41;t=6.93、8.04、9.10,P<0.05);LIPUS处理ADSC并注射后,ADSC增殖能力高于ADSC-ICI及LIPUS单独治疗组、CNI组(6.50±0.76比3.78±0.88、3.23±0.63、1.17±0.38,F=85.23,P<0.05)高于CNI组和ADSC-ICI组及LIPUS治疗组;ADSC-ICI组及LIPUS治疗组阴茎组织血小板内皮细胞黏附因子(CD31)、内皮型NO合酶(eNOS)、α肌动蛋白(a-SMA)及类肌钙蛋白(Calponin1)表达高于未CNI组、ADSC-ICI组及LIPUS治疗组(3.34±0.16比1.12±0.15、1.87±0.24、2.51±0.14,F=76.46,P<0.05;2.24±0.20比0.98±0.08、1.30±0.09、1.93±0.13,F=144.40,P<0.05;2.71±0.14比1.07±0.24、1.64±0.32、2.01±0.20,F=68.23,P<0.05;2.42±0.12比1.20±0.10、1.48±0.09、2.10±0.10,F=235.50,P<0.05)。LIPUS+ADSC-ICI治疗组后海绵体组织中整合素β1(Integrin)水平升高�ObjectiveTo explore the efficacy and molecular mechanisms of low-intensity pulsed ultrasound(LIPUS)in enhancing adipose-derived stem cell(ADSC)intracavernosal injection(ICI)for the treatment of cavernous nerve injury-induced erectile dysfunction(CNI-ED).MethodsA rat model of CNI-ED was established surgically and divided into five groups(25 rats in total),5 rats in each group:Sham group,Cavernous Nerve Injury(CNI)group,ADSC-ICI treatment group,LIPUS treatment group,and LIPUS combined with ADSC-ICI treatment(LIPUS+ADSC-ICI)group.Erectile function was evaluated by measuring intracavernosal pressure(ICP)/mean arterial pressure(MAP).Using 5-ethynyl-2’-deoxyuridine(EdU)labeling,Western blotting,hematoxylin-eosin(HE)staining,Masson staining,and cell viability analysis,we explored cellular phenotypes and molecular mechanisms.comparisons between two groups were conducted using Student’s t-test,and comparisons among multiple groups were performed using one-way analysis of variance.ResultsICP/MAP levels in the LIPUS+ADSC-ICI group exceeded CNI,ADSC-ICI,or LIPUS groups(0.79±0.06 vs.0.51±0.02,0.59±0.02,0.36±0.05,F=106.30,P<0.05).Inflammation and fibrosis in penile tissue were lower in the LIPUS+ADSC-ICI group than in CNI,ADSC-ICI,or LIPUS groups(31.13±2.05 vs.80.70±4.30,70.36±3.83,56.35±3.37,F=472.10,P<0.05).At 1st,3rd and 5th day after injection,ADSC retention in LIPUS+ADSC-ICI group was higher than that in ADSC group(6.49±0.78 vs.3.43±0.61;5.04±0.69 vs.2.04±0.46;4.09±0.54 vs.1.36±0.41,t=6.93,8.04,9.10,P<0.05);The proliferation capacity of ADSC after LIPUS treatment and injection was higher than that of ADSC-ICI,LIPUS alone treatment group or CNI group(6.50±0.76 vs.3.78±0.88,3.23±0.63,1.17±0.38,F=85.23,P<0.05).Platelet and endothelial cell adhesion molecule 1(CD31),endothelial nitric oxide synthases(eNOS),alpha smooth muscle actin(a-SMA),and calponin1 expression were higher in the LIPUS+ADSC-ICI group than CNI,ADSC-ICI,or LIPUS groups(3.34±0.16 vs.1.12±0.15,1.87±0.24,2.51±0.14,F=76.46,P<0.05;2.24±0

关 键 词：低强度脉冲超声 勃起功能障碍 海绵体神经损伤 脂肪源性干细胞 

分 类 号：R698.1[医药卫生—泌尿科学]