Leonurine combined with bone marrow mesenchymal stem cell transplantation in the treatment of intrauterine adhesions / 中国组织工程研究

ABSTRACT

BACKGROUND:Increasing evidence has demonstrated that bone marrow mesenchymal stem cel (BMSC) transplantation can promote skin, liver and lung repair in animal models; andLeonurus sibiricus L. has the ability of promoting blood circulation and regulating menstruation. OBJECTIVE: To investigate the therapeutic effect of BMSC transplantation with leonurine on intrauterine adhesions (IUA) in rabbits and the relevant mechanism of action. METHODS: After modeled using dual injury method, rabbit models of IUA were randomly divided into five groups sham-operated group (sham), model group (IUA), BMSC transplantation group, leonurine treatment group and combined treatment group (BMSCs+leonurine). Rabbits in the sham group were only given normal saline rinsing after hysterotomy, while those in the latter three groups were correspondingly given intrauterine BMSC transplantation or/and intragastric administration of 4 mg/kg leonurine for 14 days. Morphological changes of the endometrium were observed using hematoxylin-eosin staining, and expression levels of transforming growth factor β protein, Smad3 protein and interferon-γ mRNA were detected using immunohistochemical staining and real-time fluorescence quantitative PCR, respectively. RESULTS AND CONCLUSION:Compared with the model group, the degree of IUA was al significantly improved in the other groups, especialy in the combined treatment group. Moreover, BMSC transplantation, leonurine treatment and their combined use al could inhibit IUA-induced increase of transforming growth factorβ and Smad3 protein expression and IUA-induced decrease of interferon-γ mRNA level. Importantly, al these alternations were much more pronounced in the combined treatment group. Our results show that the combined use of BMSC transplantation and leonurine treatment can exert a synergistic effect in the improvement of IUA through the transforming growth factor β/Smad3 pathway.