The Therapeutic Effects And Underlying Mechanisms Of Intrauterine Perfusion Of G-CSF On Rat Model Of Thin Endometrium

Objective: To explore the improving efficacy and underlying mechanisms of intrauterine perfusion of G-CSF on thin endometrium rat model,and to provide experimental evidence for clinical application of G-CSF on thin endometrium.Methods: 20 sexually-mature（6-8 week）female Sprague Dawley（SD）rats were used in this study,half of them were randomly selected as group I by perfusing absolute ethanol（AE）in one side of uterine cavity and same dose of normal saline（NS）in another side for both 5 minutes;another 10 rats were selected as group II by perfusing AE into bilateral uterine cavities for 5 minutes.10 rats of group I were killed 3 estrous cycles after model establishment;at the same time,10 rats of group II were perfused with G-CSF（30 μg/kg）in one side of uterine cavity and same dose of NS in another side for 5 minutes.After another 3 estrous cycles,those 10 rats were all killed to obtain uterine samples.HE and IHC staining were used to prove the models were successfully established by detecting the change of endometrial thickness and the expression of cytokeratin 19（CK19）and vimentin（Vim）.Then the relative expression of VEGF and LIF were also tested by q RT-PCR and Western-blot on the level of molecular biology.Results:1.The endometrial thickness of group A（normal endometrium）,group B（thin endometrium）,group C（NS therapy）and group D（G-CSF therapy）were as follows: 678.11±14.79 μm 、 319.91±26.33 μm 、 368.13±19.51 μm 、565.17±19.44 μm.There were significant differences between group A and group B,also between group C and group D（all P < 0.05）.2.The mean optical density（MOD）of CK19 in four groups were as follows: 0.43±0.02、0.14±0.03、0.13±0.03、0.41±0.03;the MOD of Vim in four groups were as follows: 0.50±0.02、0.16±0.03、0.19±0.02、0.40±0.02.There were significant differences group A and group B,also between group C and group D（all P < 0.05）.3.The relative m RNA expression levels of VEGF in four groups were as follows: 1.013±0.070、0.411±0.027、0.483±0.040、0.936±0.114;the relative m RNA expression levels of LIF in four groups were as follows: 1.012±0.071、0.330±0.105、0.361±0.084、1.036±0.104.There were significant differences group A and group B,also between group C and group D（all P < 0.05）.4.The protein expression of VEGF in four groups were as follows:0.437±0.016、0.300±0.016、0.281±0.016、0.399±0.013;the protein expression of LIF in four groups were as follows: 0.331±0.017、0.202±0.006、0.201±0.005、0.287±0.011.There were significant differences group A and group B,also between group C and group D（all P < 0.05）.Conclusions: Intrauterine perfusion of G-CSF can effectively improve the endometrial thickness as well as the relative expression of CK19 and Vim in rat model of thin endometrium and its underlying mechanisms may be related to the promotion of angiogenesis by VEGF and improvement of endometrial receptivity by LIF.