[Study on human umbilical cord mesenchymal stem cells transplantation in treatment of stress urinary incontinence in rats].

OBJECTIVE: To investigate the feasibility and effectiveness of human umbilical cord mesenchymal stem cells (HUCMSC) transplantation in the treatment of female stress urinary incontinence (SUI) in rats. METHODS: The 14 female SD rats of SUI model were established by vaginal balloon dilation after birth and maintain this status for four hours bilateral ovariectomy were performed after two weeks and were routinely reared for two months, then 12 SUI rat model were made. Two months later, transfected with plasmid pEGFP-N1 of HUCMSC were injected into the region surrounding the urinary tract matched with saline injection as control group. To get genitourinary tissue after testing urodynamic indicators, and observe the pathological changes of the bladder, urethra and the surrounding tissue; fluorescent cell of the experimental groups specimens were observed by fluorescence microscope. RESULTS: The leak point pressure(LPP) was (23.8 ± 4.2) mm Hg(1 mm Hg = 0.133 kPa) of the SUI rats. Transplanting mesenchymal stem cells of SUI rats, the positive rate of sneeze test was 1/6 in SUI group and 5/6 in control group, which reached statistical significance (P < 0.05); LPP was (30.6 ± 2.8) mm Hg in SUI group and (21.4 ± 7.0) mm Hg in control group, which reached statistical significance (P < 0.05) .In SUI rate model, connective tissue content were increased in urethra and the surrounding tissue and more fluorescent cell were observed. CONCLUSIONS: A rat model of female SUI was established successfully through postpartum vaginal balloon dilation and bilateral ovariectomy. MSC can be survived and proliferated in the urethral and the surrounding tissue of injured rats, and improve the urodynamic indicators and the positive rate of sneeze test. Morphology shows renovation of the support structures around the urethra.

Lipoxin A4 depresses inflammation and promotes autophagy via AhR/mTOR/AKT pathway to suppress endometriosis.

BACKGROUND: Endometriosis is a benign gynecological disease with the feature of estrogen dependence and inflammation. The function of autophagy and the correlation with inflammation were not yet revealed. METHODS: Autophagosomes were detected by transmission electron microscopy. Gene Expression Omnibus (GEO) database was referred to analyze the expression of autophagy-related genes. Quantification of mRNA and protein expression was examined by qRT-PCR and Western Blot. Immunohistochemistry was performed to explore the expression of proteins in tissues. The mouse model of endometriosis was performed to analyze the autophagic activity and effect of LXA4. RESULTS: The expression of autophagy-related genes in endometriotic lesions were unusually changed. The number of autophagosomes and LC3B-II expression was diminished, and p62 was increased in ectopic lesions from both patients and mice. Interleukin 1ß (IL1ß) attenuated the expression of LC3B and promoted the level p62. The autophagy activator MG-132 upregulated the expression of LC3B and reduced IL1ß, IL6, and p62. LXA4 reversed the inhibitory effect of IL1ß on the expression of LC3B and p62, and blocking the receptor of LXA4 AhR (aryl hydrocarbon receptor) resulted in the incapacitation of LXA4 to influence the effect of IL1ß. LXA4 depressed the phosphorylation of AKT and mTOR to against IL1ß, and blocking AhR negatively regulated the effect of LXA4 on AKT/mTOR pathway. LXA4 reduced the ectopic lesions and the expression of IL1ß and p62, but enhanced LC3B-II in endometriotic mouse models. CONCLUSION: In endometriosis, increased inflammation of ectopic lesions prominently depresses autophagy. LXA4 could regulate autophagy by suppressing inflammatory response through AhR/AKT/mTOR pathway.