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Study On The Efficacy And Mechanism Of FGF2 Inhibitors On Endometriosis

Posted on:2022-01-22Degree:MasterType:Thesis
Country:ChinaCandidate:M M ZhangFull Text:PDF
GTID:2504306515981079Subject:Clinical Laboratory Science
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Research purposes To construct a C57BL/6 mouse model of endometriosis,explore the therapeutic effects of different concentrations of FGF2 inhibitors on endometriosis model mice,and to explore the effects of FGF2 inhibitors in the treatment of endometriosis The possible mechanism was studied.Provide a new treatment strategy for the treatment of clinical endometriosis.Research method1.The subjects of the study were 8-week-old female C57BL/6 mice.The endometriosis model was constructed by the method of allograft and abdominal cavity implantation,and 6 models were randomly executed at 7,14,21,and 28 days after the model was constructed.In mice,observe the size of the ectopic lesions and perform HE staining of the ectopic lesions to determine the construction of the endometriosis model,which provides a basis for subsequent drugs to act on endometriosis mice.2.The endometriosis model mice were randomly divided into model group,FGF2 inhibitor low-dose group,FGF2 inhibitor medium-dose group,FGF2 inhibitor high-dose group and gestrinone group.Drug treatment was started three weeks after the endometriosis model was established.After 4 weeks of administration,the mice were sacrificed by cervical dislocation,and the mice were weighed,and their hearts,livers,spleen,lungs and kidneys were taken to measure their weight.Weigh and calculate the organ coefficient.To determine the side effects of FGF2 inhibitors on mice.3.The ectopic lesions were collected from each group of mice,and the size of the ectopic lesions was measured.HE staining was performed to judge the construction of the endometriosis model;Masson staining was used to judge the degree of fibrosis of the ectopic lesions,and immunohistochemistry was used to detect the α-SMA,Col-1,CTGF,and FN proteins in the ectopic lesions of each group of mice Location and expression;RT-PCR was used to detect the m RNA expression of α-SMA,Col-1,CTGF and FN in ectopic lesions of mice in each group.Analyze and judge the effect of FGF2 inhibitors on endometriosis-related pain,ectopic lesion growth and fibrosis degree.4.Western blot detection of FGF2 and FGFR2 protein expression in ectopic lesions of each group of mice RT-PCR detection of FGF2 and FGFR2 m RNA expression in ectopic lesions of each group of mice.Explore the possible mechanism of FGF2 inhibitors in the treatment of endometriosis.Research result1.C57BL/6 mouse allograft abdominal cavity implantation of endometrial fragments has a high success rate and saves time and effort.It is a feasible method for modeling;the ectopic lesions have reached a steady state on the 21 st day after modeling.Provide guidance for follow-up drug treatment intervention time;2.After 4 weeks of drug administration,the weight,heart,liver,spleen,lung and renal organ coefficients of the mice in each group were not statistically different,and the toxic and side effects of FGF2 inhibitors were small;3.FGF2 inhibitors can prolong the hot plate latency of endometriotic mice,reduce the size of ectopic lesions,and inhibit the expression of fibrosis indicators α-SMA,Col-1,CTGF,FN,and the larger the dose,The more obvious the effect.Shows that FGF2 inhibitors can relieve pain related to endometriosis,inhibit the growth and proliferation of ectopic lesions,and inhibit the occurrence and development of fibrosis;4.FGF2 inhibitors can inhibit the expression of FGF2 and FGFR2 m RNA and protein in ectopic lesions,indicating that FGF2 inhibitors treat endometriosis by inhibiting the expression of FGF2 and FGFR2.Conclusion This study investigated the effects of FGF2 inhibitors on the hot plate latency,the size of ectopic lesions,the expression of fibrosis indicators and the weight and organ coefficient of mice with endometriosis,indicating that FGF2 inhibitors can alleviate the endometriosis.Symptom-related pain,inhibit the growth and proliferation of ectopic lesions and inhibit the occurrence and development of fibrosis,and its toxic and side effects are small.FGF2 inhibitors are expected to be used in clinical treatment of endometriosis.
Keywords/Search Tags:Endometriosis, FGF2, FGF2 inhibitor, Fibrosis
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