摘要
目的:探讨双氢青蒿素对非细菌性前列腺炎(Chronic non-bacterial prostatitis,CNP)的治疗效果及其对骨髓间充质干细胞(BMSCs)归巢的影响.方法:选取30只9～11 w龄雄性C57BL/6小鼠,随机抽取6只作为正常对照组,剩余24只注射消痔灵.建立慢性非细菌性前列腺炎小鼠模型.将造模成功后的小鼠随机分为模型对照组、骨髓间充质干细胞组、双氢青蒿素5 mg/kg+骨髓间充质干细胞组和双氢青蒿素15 mg/kg+骨髓间充质干细胞组,每组6只.采用膀胱穿刺测压法行小鼠膀胱排尿功能检测;免疫荧光法检测红色荧光蛋白(RFP)阳性细胞在前列腺组织中的表达情况;HE染色检测小鼠前列腺组织病理状态;天狼星红染色检测小鼠前列腺组织胶原累积情况;ELISA法检测小鼠前列腺组织炎性因子肿瘤坏死因子α(TNF-α)、白介素(IL)-1β和趋化因子COX2、CXCL9、CXCL10、CXCL11的含量.结果:膀胱穿刺测压法结果显示,与正常对照组相比,模型对照组和骨髓间充质干细胞组小鼠膀胱最大容量(vm)和最大排尿压力(PMV)降低,残余尿量(vR)增加,CNP小鼠膀胱组织大部分腺体炎细胞浸润,胶原积累增多,前列腺组织TNF-α、IL-1β、C0X2、CXCL9、CXCL10、CXCL11含量明显增加(P＜0.05或P＜0.01);与模型对照组相比,双氢青蒿素各组vm和PMV均增加,vR减少;腺体炎细胞浸润和胶原积累减少;双氢青蒿素5 mg/kg+骨髓间充质干细胞组前列腺组织TNF-α、IL-1β、COX2、CXCL11的含量明显降低,双氢青蒿素15 mg/kg+骨髓间充质干细胞组前列腺组织TNF-α、IL-1β、COX2、CXCL9、CXCL10、CXCL11的含量明显降低(P＜0.05或P＜0.01).结论:双氢青蒿素治疗可剂量依赖性地促进骨髓间充质干细胞的归巢,改善小鼠的CNP相关症状,降低CNP小鼠前列腺组织炎症水平和纤维组织增生,降低炎性因子和趋化因子的水平.双氢青蒿素和骨髓间充质干细胞联合治疗可极大改善CNP病情.
Abstract
Objective:To investigate the effect of dihydroartemisinin on non-bacterial prostatitis(CNP)and the homing of bone marrow mesenchy-mal stem cells(BMSCs).Methods:Thirty male C57BL/6 mice aged 9～11 weeks were included.Six of them were randomly selected as normal control group,and the remaining 24 mice were injected with Xiaozhiling to establish a chronic CNP model.After successful modeling,the mice were randomly divided into model group,BMSCs group,dihydroartemisinin(5 mg/kg)+BMSCs group and dihydroartemisinin(15 mg/kg)+BMSCs group,six in each group.The urinary bladder function of mice was detected by bladder manometry.The expression of red fluorescent protein(RFP)positive cells in prostate tissue was detected by immunofluorescence.HE staining and Sirius red staining were used to observe the pathological state of mouse prostate tissue and the collagen accumulation,respectively.The levels of inflammatory factors(TNF-α,IL-1β)and chemokines(COX2,CXCL9,CXCL10,CXCL11)in mouse prostate tissue were detected by ELISA.Results:Bladder manometry showed that compared with the normal control group,the model group and BMSCs group had decreased bladder maximum volume(MBC)and maximum voiding pressure(MVP),and increased residual urine volume(RV).In addition,the model group and BMSCs group presented infiltration of most glandular inflammatory cells and increased collagen accumulation in bladder tissues,as well as up-regulated TNF-α,IL-1β,COX2,CXCL9,CXCL10 and CXCL11(P＜0.05 or P＜0.01).Compared with the conditions in model group,MBC and MVP were elevated while RV was reduced in BMSCs group,and the infiltration of glandular inflammatory cells and collagen accumulation were de-creased.TNF-α,IL-1β,COX2,and CXCL11 were down-regulated in dihydroartemisinin(5 mg/kg)+BMSCs group,while TNF-α,IL-1β,COX2,CXCL9,CXCL10,and CXCL11 were down-regulated in dihydroartemisinin(15 mg/kg)+BMSCs group(P＜0.05 orP＜0.01).Con-clusion:Dihydroartemisinin promotes the homing of BMSCs in a dose-dependent manner,alleviates CNP-related symptoms,reduces inflamma-tion and fibrous tissue hyperplasia in prostate tissue,and down-regulates the inflammatory factors and chemokines of CNP mice.Dihydroarte-misinin combined with BMSCs can greatly improve the condition of CNP.
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