Effect of local injection of human umbilical cord mesenchymal stem cells combined with sodium hyaluronate gel in the treatment of intrauterine adhesions in rats and its mechanism
Objective To investigate the effect of local injection of human umbilical cord mesenchymal stem cells(hUC-MSCs)combined with sodium hyaluronate gel in the treatment of intrauterine adhesion in rats and its possible mecha-nisms.Methods Twenty-five specific pathogen-free female Sprague Dawley rats were divided into a blank control group,an intrauterine adhesion group,a sodium hyaluronate group,an hUC-MSCs group,and an hUC-MSCs+sodium hyaluronate group according to the random number table method,with 5 rats in each group.The rats in the blank control group received no treatment,while the rats in the rest four groups were injected with 950 mL·L-1 ethanol to prepare intrauterine adhesion models.One week following the establishment of the intrauterine adhesion models,100 μL of 1 × 1010 L-1 hUC-MSCs suspension was injected into the bilateral uterine horns of rats in the hUC-MSCs group and hUC-MSCs+sodium hyaluronate group;and 100 μL of normal saline was injected into the bilateral uterine horns of rats in the intrauterine adhesion group and sodium hyaluronate group.Subsequently,300 μL of sodium hyaluronate gel was injected into the bilateral uterine horns of rats in the sodium hyaluronate group and hUC-MSCs+sodium hyaluronate group;while,the same amount of normal saline was injected into the bilateral uterine horns of rats in the intrauterine adhesion group and hUC-MSCs group.After three days of intervention,all female rats in the five groups were combined with mature male rats possessing reproductive ability at a ratio of 1∶2 and then mated.The vaginal plugs of the female rats were observed for seven days to confirm successful mating.The abdominal aortic blood from pregnant rats in the five groups was extracted,and the serum levels of interleukin-6(IL-6)and interleukin-8(IL-8)were determined by using enzyme-linked immunosorbent assay.After blood collection,the rats were euthanized with excessive anesthesia,and subsequently,the uterus was removed and rinsed with normal saline.Firstly,the quantity of gestational sacs was counted;then,the endometrial tissues were meticulously separated,and the expression levels of matrix metalloproteinase-9(MMP-9)and transforming growth factor β,(TGF-β1)in the endometrial tissues of the rats were detected by using Western blot.Results The number of gestational sacs in rats in the intrauterine adhesion group,sodium hyaluronate group,hUC-MSCs group,and hUC-MSCs+sodium hyaluronate group was significantly fewer than that in the blank control group,the number of gestational sacs in rats in the sodium hyaluronate group,hUC-MSCs group,and hUC-MSCs+sodium hyaluronate group was significantly more than that in the intrauterine adhesion group,and the number of gestational sacs in rats in the hUC-MSCs+sodium hyaluronate group was significantly higher than that in the sodium hyaluronate group and the hUC-MSCs group(P＜0.05);there was no significant difference in the number of gestational sacs in rats between the sodium hyaluronate group and the hUC-MSCs group(P＞0.05).The serum IL-6 and IL-8 levels of rats in the intrauterine adhesion group,sodium hyaluronate group,hUC-MSCs group,and hUC-MSCs+sodium hyaluronate group were significantly higher than those in the blank control group,the serum IL-6 and IL-8 levels of rats in the sodium hyaluronate group,hUC-MSCs group,and hUC-MSCs+sodium hyaluronate group were significantly lower than those in the intrauterine adhesion group,and the serum IL-6 and IL-8 levels of rats in the hUC-MSCs+sodium hyaluronate group were significantly lower than those in the sodium hyaluronate group and the hUC-MSCs group(P＜0.05);there was no significant difference in the serum IL-6 and IL-8 levels of rats between the sodium hyaluronate group and the hUC-MSCs group(P＞0.05).The relative expression level of TGF-β,in the endometrial tissues of rats in the intrauterine adhesion group,sodium hyaluronate group,hUC-MSCs group,and hUC-MSCs+sodium hyaluronate group was significantly higher than that in the blank control group,while the relative expression level of MMP-9 was significantly lower than that in the blank control group(P＜0.05).The relative expression level of TGF-β,in the endometrial tissues of rats in the sodium hyaluronate group,hUC-MSCs group,and hUC-MSCs+sodium hyaluronate group was significantly lower than that in the intrauterine adhesion group,while the relative expression level of MMP-9 was significantly higher than that in the intrauterine adhesion group(P＜0.05).The relative expression level of TGF-β,in the endometrial tissues of rats in the hUC-MSCs+sodium hyaluronate group was significantly lower than that in the sodium hyaluronate group and the hUC-MSCs group,while the relative expression level of MMP-9 was significantly higher than that in the sodium hyaluronate group and the hUC-MSCs group(P＜0.05).There was no significant difference in the relative expression levels of TGF-β,and MMP-9 in the endometrial tissues of rats between the sodium hyaluronate group and the hUC-MSCs group(P＞0.05).Conclusion The combined injection of hUC-MSCs and sodium hyaluronate gel may up-regulate the expression level of MMP-9 protein and reduce the levels of TGF-β1 and inflammatory factors IL-6 and IL-8 in the endometrial tissues of rats with intrauterine adhesion,thereby repairing the damaged endometrium and increasing the number of gestational sacs.
维普
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