Effect Of Polydatin On Improving Intrauterine Adhesions In Mice And Its Mechanism

Objective: Intrauterine adhesions(IUA),also known as Asherman syndrome,is an endometrial basal layer injury caused by infection,trauma,etc.,abnormal endometrial repair,resulting in scarring of the uterine cavity or cervical canal,causing uterine morphology changes.,menstrual flow reduction,amenorrhea and recurrent abortion and even infertility and other related clinical symptoms.At present,with the improvement of diagnosis and treatment technology,the detection rate of intrauterine adhesions is getting higher and higher,but there are limited methods for clinical treatment of intrauterine adhesions: including hysteroscopic adhesionlysis,postoperative estrogen prevention and treatment,surgery The posterior balloon supports the treatment and anti-adhesion membrane.Polydatin has been found to have a therapeutic effect in fibrotic diseases of other tissues and organs.Therefore,this paper mainly studies the study of polydatin in improving the model of intrauterine adhesion disease in mice.To explore the causes and progress of patients with intrauterine adhesions and the molecular mechanism of the disease,provide a new perspective for the clinical diagnosis and treatment of intrauterine adhesions,and provide new ideas for infertility caused by intrauterine adhesions.Methods: We established a mouse model of intrauterine adhesions by the dual effects of mechanical injury and lipopolysaccharide(LPS)inflammation.All mice were divided into 6 groups,8 in each group: normal control group,sham operation group,model group,low dose group of polydatin(5mg/kg),medium dose of polydatin(10mg/kg)and High dose group of polydatin(20mg/kg).After the end of modeling,different doses(5mg/kg,10mg/kg,20mg/kg)of polydatin were given;no intervention was given in the control group,the same volume of normal saline was given in the sham operation group;mice were collected after the end of 14 days of treatment.The bilateral uterus was evaluated for success.The uterine tissue was analyzed by paraffin section Masson staining to analyze the deposition degree of collagen fibers at different concentration gradients;immunohistochemical analysis of NF-?B,TGF-?,Smad2/3 and ?-SMA protein expression levels to determine whether polydatin can reduce the expression of these fibrosis-related proteins;qPT-PCR detection of uterine tissue(TGF-?1,NF-?B,P38 and MSK)expression levels of each gene,to observe whether polydatin can regulate the occurrence of fibrosis at the genetic level.Results: Different doses(5mg/kg,10mg/kg,20mg/kg)of polydatin were applied to IUA mice.After 14 days of administration,it was found that the concentration of polydatin had no significant effect on the weight of IUA mice.There was no significant difference in body weight gain between the groups;it was found by Masson that polydatin can significantly reduce uterine collagen fiber deposition(P<0.05)in IUA mice,improve adhesion,and decrease with increasing drug concentration;There was no difference between the number of endometrial glands in the low dose group of polydatin and the number of glands in the model group.Other concentrations of polydatin group could repair the endometrium of IUA mice caused by mechanical injury and inflammatory stimulation.Compared with the model group,the number of glands increased,and the difference was statistically significant(P<0.05).Protein expression analysis showed that the expression ratio of TGF-?1,NF-?B,?-SMA and Smad2/3 protein in the uterus of the treatment group was compared.The group was significantly reduced(P<0.05),and TGF-?1,NF-?B were consistent with the results of RNA analysis: the expression levels of inflammatory factors P38 and MSK were significantly decreased in the treatment group of polydatin,and there were significant differences compared with the control group(P<0.05).Conclusion: Polydatin can improve the degree of intrauterine adhesions in IUA mice,reduce tissue collagen fibrosis,reduce intimal adhesions,and promote glandular recovery;and down-regulate adhesion-associated and inflammation-related genes(TGF-?1,NF-?B)The expression levels of NF-?B,P38 and MSK inhibited the expression of inflammatory factors and adhesion factors in IUA mice,significantly improved adhesion in IUA mice,promoted intimal repair and gland regeneration,which may improve IUA mice.Pregnancy rate;plays an active role in the treatment of IUA mice,providing a new perspective for the treatment of intrauterine adhesions.