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纸质出版:2015
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韩广玮,申雪晴,高文宏,崔栋,尚永刚,刘城城,易善红.超声复合微泡促进骨髓间充质干细胞归巢对大鼠前列腺炎的治疗作用[J].陆军军医大学学报(原第三军医大学学报),2015,37(11):1108-1113.
Han Guangwei,Shen Xueqing,Gao Wenhong,Cui Dong,Shang Yonggang,Liu Chengcheng,Yi Shanhong.Efficiency of prostate-targeted homing of bone marrow mesenchymal stem cells in treatment of rat prostatitis mediated by microbubble-enhanced ultrasound[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(11):1108-1113.
韩广玮,申雪晴,高文宏,崔栋,尚永刚,刘城城,易善红.超声复合微泡促进骨髓间充质干细胞归巢对大鼠前列腺炎的治疗作用[J].陆军军医大学学报(原第三军医大学学报),2015,37(11):1108-1113. DOI:
Han Guangwei,Shen Xueqing,Gao Wenhong,Cui Dong,Shang Yonggang,Liu Chengcheng,Yi Shanhong.Efficiency of prostate-targeted homing of bone marrow mesenchymal stem cells in treatment of rat prostatitis mediated by microbubble-enhanced ultrasound[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(11):1108-1113. DOI:
目的 研究静脉注射骨髓间充质干细胞(bone marrow mesenchymal stem cells
BMSCs)对大鼠前列腺炎的治疗作用。 方法 贴壁法分离、培养、扩增BMSCs。将50只SD大鼠按随机数字表法分为慢性细菌性前列腺炎(chronic bacterial prostatitis
CBP)组、CBP+BMSCs组、CBP+超声复合微泡(microbubble-enhanced therapeutic ultrasound,MEUS)组、CBP+MEUS+BMSCs组和正常对照组,每组10只。在小动物超声引导下向大鼠前列腺两侧叶内注射大肠埃希菌建立前列腺炎症模型,注入细菌1~14 d为急性炎症期,4~12周为慢性炎症期,对照组注入等量PBS。建模28 d后经静脉单纯注入BMSCs、单纯行MEUS及行MEUS+注入BMSCs,活体成像观察BMSCs向前列腺归巢情况。观察移植BMSCs 2周后大鼠前列腺组织病理学变化并作炎症评分,RT-PCR检测炎症因子IL-1β、TNF-α mRNA,ELISA检测IL-1β、TNF-α蛋白含量,统计分析各组表达差异。 结果 前列腺组织病理学提示CBP组、CBP+BMSCs组、CBP+MEUS组前列腺呈典型炎症病理变化,腺管上皮增生,层次增加,炎细胞浸润,纤维组织增生,而CBP+MEUS+BMSCs组大鼠前列腺炎症明显减轻。RT-PCR检测结果提示CBP组炎症因子IL-1β(0.282±0.067)、TNF-α(0.631±0.116),CBP+BMSCs组IL-1β(0.893±0.117)、TNF-α(0.876±0.137),CBP+MEUS组IL-1β(0.683±0.097)、TNF-α(0.814±0.127)高于正常对照组IL-1β(0.282±0.067)、TNF-α(0.256±0.059)和CBP+MEUS+BMSCs组IL-1β(0.322±0.086)、TNF-α(0.313±0.079)(P0.05);ELISA检测结果显示CBP组炎症因子IL-1β[(315.14±86.08)pg/mL]、TNF-α[(86.41±24.32)pg/mL],CBP+BMSCs组IL-1β[(278.87±72.04)pg/mL]、TNF-α[(67.77±16.98)pg/mL],CBP+MEUS组IL-1β[(321.24±93.12)pg/mL]、TNF-α[(79.14±19.17)pg/mL]含量均显著高于正常对照组[IL-1β(43.36±11.35)pg/mL、TNF-α(13.26±3.97)pg/mL]和CBP+MEUS+BMSCs组[IL-1β(65.34±17.23)pg/mL、TNF-α(19.94±5.37)pg/mL],差异有统计学意义(P0.01),而CBP+MEUS+BMSCs组与正常对照组比较差异无统计学意义(P0.05)。 结论 超声复合微泡促进BMSCs向前列腺归巢,能够减轻前列腺炎症反应,可能为前列腺炎的治疗带来新策略。
Objective To investigate the efficiency of venous injection of bone marrow mesenchymal stem cells (BMSCs) in treatment of rat prostatitis. Methods Rat BMSCs were separated with successive adherence method
and then cultured and amplified. Fifty SD rats were randomized into 5 groups (n=10): chronic bacterial prostatitis (CBP) group
CBP+BMSCs group
CBP+microbubble-enhanced therapeutic ultrasound (MEUS) group
CBP+MEUS+BMSCs group and normal control group. The rats in the other 4 groups except for control were injected with E.coli into both sides of prostate under ultrasound guidance to establish prostatitis model (1-14 d after injection was regarded as acute inflammation period
and 4-12 weeks as chronic inflammation period). The rats from control group were injected with the same volume of PBS. Intravenous injection of BMSCs
MEUS and MEUS+BMSCs was performed into prostatitis rats in 28 d after E.coli injection. BMSCs homing to the prostate were observed by small living animal imaging technology. Pathomorphological changes of rat prostate tissue were observed by light microscopy in 2 weeks after BMSCs injection. The mRNA and protein levels of IL-1β and TNF-α in the prostates were determined by RT-PCR and ELISA
respectively. Results Histopathological evaluation showed that typical pathological inflammation were observed in CBP
CBP+BMSCs and CBP+MEUS groups
including the change of gland structure
interstitial edema
inflammatory cells infiltration and fibrous hyperplasia
while pathological changes were relieved obviously in CBP+MEUS+BMSCs group. The mRNA expression levels of IL-1β and TNF-α were obviously higher in CBP group (0.282±0.067 and 0.631±0.116)
CBP+BMSCs group (0.893±0.117 and 0.876±0.137)
and CBP+MEUS group (0.683±0.097 and 0.814±0.127) than those in control group (0.282±0.067 and 0.256±0.059) and CBP+MEUS+BMSCs group (0.322±0.086 and 0.313±0.079
all P0.05). The protein contents of IL-1β and TNF-α were remarkably higher in CBP group (315.14±86.08 and 86.41±24.32 pg/mL)
CBP+BMSCs group (278.87±72.04 and 67.77±16.98 pg/mL)
and CBP+MEUS group (321.24±93.12 and 79.14±19.17 pg/mL) than those in control group (43.36±11.35 and 13.26±3.97 pg/mL) and CBP+MEUS+BMSCs group (65.34±17.23 and 19.94±5.37 pg/mL
all P0.01). While
there was no statistically difference in control group and CBP+MEUS+BMSCs group (P0.05). Conclusion MEUS promotes the prostate-targeted transplantation of BMSCs
which can reduce the prostatitis-induced inflammation reaction. This may bring a new strategy for the treatment of prostatitis.
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