Huang S L, Fu D L, Li H C, Zhang P, Chong T
Department of Urology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, 710004, Shaanxi Province, People's Republic of China.
Int Urol Nephrol. 2016 May;48(5):717-23. doi: 10.1007/s11255-016-1227-x. Epub 2016 Feb 2.
To investigate the effect of rapamycin on TGFβ1 and MMP1 expression in a rabbit model of urethral stricture.
Twenty-four adult New Zealand male rabbits underwent an electrocoagulation of the bulbar urethra with a 13Fr pediatric resectoscope. Then rabbits were randomly divided into three groups: (1) normal control group: normal saline (NS), (2) the vehicle control group: dimethyl sulfoxide (DMSO), and (3) the treatment group: effective-dose rapamycin in DMSO (Ra), with 12, 6, and 6 rabbits in each group, respectively. Drugs were given by urethral irrigation daily for 4 weeks. Urethral tissue was harvested for histological and molecular analyses. TGFβ1 and MMP1 expression levels were evaluated by real-time quantitative PCR and immunohistochemistry.
Ten, six, and six rabbits were evaluated finally in Ra, DMSO, and NS group, respectively. Histological examination revealed the distribution of fibrosis and the degree of collagen deposition in the Ra group were smaller and slighter than the two control groups. Collagen content was significantly less in the Ra group than in the DMSO group (P < 0.001) and the NS group (P < 0.001). qRT-PCR analysis showed a higher expression of MMP1 mRNA in the Ra group than in the DMSO group (P < 0.001) and the NS group (P < 0.001). Immunohistochemistry showed the protein levels of MMP1 in the Ra group were significantly increased when compared with the DMSO group (P < 0.01) and the NS group (P < 0.01). On the other hand, no statistical difference could be found between every two groups in both mRNA and protein levels of TGFβ1.
Rapamycin enhances the expression of MMP1 in a rabbit model of urethral stricture, but has no direct effect on the expression of TGFβ1.
研究雷帕霉素对兔尿道狭窄模型中转化生长因子β1（TGFβ1）和基质金属蛋白酶1（MMP1）表达的影响。
24只成年新西兰雄性兔用13Fr小儿电切镜对球部尿道进行电凝术。然后将兔随机分为三组：（1）正常对照组：生理盐水（NS）；（2）溶剂对照组：二甲基亚砜（DMSO）；（3）治疗组：DMSO中有效剂量的雷帕霉素（Ra），每组分别为12只、6只和6只。每天通过尿道灌注给药，持续4周。采集尿道组织进行组织学和分子分析。通过实时定量PCR和免疫组织化学评估TGFβ1和MMP1的表达水平。
最终分别对Ra组、DMSO组和NS组的10只、6只和6只兔进行了评估。组织学检查显示，Ra组纤维化分布及胶原沉积程度均小于两个对照组。Ra组胶原含量明显低于DMSO组（P < 0.001）和NS组（P < 0.001）。qRT-PCR分析显示，Ra组MMP1 mRNA表达高于DMSO组（P < 0.001）和NS组（P < 0.001）。免疫组织化学显示，与DMSO组（P < 0.01）和NS组（P < 0.01）相比，Ra组MMP1蛋白水平显著升高。另一方面，TGFβ1的mRNA和蛋白水平在任意两组之间均未发现统计学差异。
雷帕霉素可增强兔尿道狭窄模型中MMP1的表达，但对TGFβ1的表达无直接影响。
