Small hairpin RNA targeting inhibition of NF-κB gene in endometriosis therapy of Macaca fascicularis
10.3760/cma.j.issn.0529-567x.2015.01.011
- VernacularTitle:shRNA靶向抑制NF-κB基因治疗食蟹猴子宫内膜异位症的研究
- Author:
Fengcheng ZHU
;
Mubiao LIU
;
Ying PAN
;
Xuefeng WANG
;
Yanying CHEN
- Publication Type:Journal Article
- Keywords:
Endometriosis;
NF-kappa B;
RNA,small interfering;
Macaca fascicularis;
Proliferating cell nuclear antigen;
Neovascularization,pathologic
- From:
Chinese Journal of Obstetrics and Gynecology
2015;50(1):48-53
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the therapeutic effect of NF-κB gene short hairpin RNA (shRNA) on endometriosis and identify the function of NF-κB on the maintenance and development of endometriosis in Macaca fascicularis.Methods The Macaca fascicularis model of endometriosis was developed,which divided into experimental group,negative control group and simple model group.The high specificity adenovirus vector mediated shRNA targeting NF-κB gene and negative control shRNA adenovirus with no-load NF-κB gene were synthesised.The experimental group injected the adenovirus which carried the NF-κB shRNA into the endometriosis lesions under laparoscopy surgery,the negative control group with no-load shRNA adenovirus and the simple models group injected with normal saline.Four weeks later after the injection,an observed operation was performed through laparoscopy and some lesions were collected.The CD34 immunohistochemistry of these lesions were done to detect the microvessel density,then the variation of the microvessel density among each group were observed.The expression of the NF-κB and proliferating cell nuclear antigen (PCNA) were detected through western blot.Results First,the Macaca fascicularis model of endometriosis was successful developed,and the experimental group has an evident atrophy in ectopic lesions compared with the previous.The lesions' microvessel density in experimental group decreased evidently compared with the negative control group and simple model group (0.002 0±0.000 3 versus 0.021 9±0.002 6 versus 0.024 5±0.003 3),and the differences was statistically significant (P<0.01).The expression of PCNA (0.37±0.17 versus 0.57±0.26 versus 0.57±0.28) and NF-κB (0.338 ± 0.174 versus 0.678 ± 0.021 versus 0.645 ±0.098) in experiment group was lower than the negative control group and simple model group,the differences were statistically significant (all P<0.01).Conclusion Through targeting suppressed the NF-κB gene expression by NF-κB shRNA,we can inhibit the development of endometriosis through reducing the ability of angiogenesis and cell proliferation of ectopic endometrial cells.