Inhibition of PDGF Expression by Clopidogrel Improves Intrauterine Adhesion in Rats
Objective:Intrauterine adhesion(IUA)is a.common disease in women of childbearing age and one of the common causes of female infertility.This study proposes whether clopidogrel can improve intrauterine adhesion in rats and its possible mechanism.Providing a theoretical basis for clinical treatment.Methods:Thirty female Sprague-Dawley rats were randomly divided into 3 groups:normal control group(NC)(n=10,gavage with normal saline),intrauterine adhesion model group(IUA)(n=10,gavage with normal saline)and clopidogrel treatment group(IUA+Clo)(n=10,gavage with clopidogrel).The mechanical damage method was used to establish the IUA model,after 7 days of modeling,the rats in the clopidogrel treatment group were treated with clopidogrel by gavage,60 mg/kg/d.Rats in the model group were given the same dose of normal saline by gavage for 7 days.Hematoxylin-eosin(HE)staining was used to detect the pathological changes of the uterus,calculate the number of endometrial glands and measure the thickness of the endometrium.Masson staining was used to detect the fibrosis of rat uterus.The expression levels of TNF-α and IL-6 in serum of rats were detected by enzyme-linked immunosorbent assay(ELISA).The expression levels of PDGF,collagen Ⅰ and α-SMA in rat uterine tissues were detected by immunohistochemistry(IHC).Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the mRNA expression levels of PDGF,collagen Ⅰ and α-SMA in uterine tissue.The protein expression levels of PDGF,collagen Ⅰ andα-SMA in uterine tissue were detected by Western blot.Results:Compared with that in the normal control group,the number of endometrial glands in the intrauterine adhesion model group reduced significantly(P＜0.05).The degree of endometrial thinning and fibrosis increased significantly(P＜0.05).Compared with that in the intrauterine adhesion model group,the number of endometrial glands in the clopidogrel treatment groups increased significantly(P＜0.05).endometrium exhibited a significant increase(P＜0.05),the levels of serum inflammatory factors TNF-α and IL-6 decreased significantly(P＜0.05).The expressions of PDGF,collagen Ⅰ and α-SMA in uterine tissue decreased significantly(P＜0.05).Conclusion:Clopidogrel can inhibit the aggregation and activation of platelets,inhibit the level of inflammation,reduce the expression of PDGF and inhibit the occurrence and progression of endometrial fibrosis in rats,Clopidogrel may be one of the drugs for the treatment of intrauterine adhesions.
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