Regangan Ligamentum Sakrouterina Saat Inpartu Meningkatkan Kejadian Prolap Uteri Pasca Persalinan Melalui Jalur Integrin

Rahajeng, - and Prof. Dr. dr. Sanarto Santoso,, DTM&H., SpMK.(K). and dr. Hidayat Sujuti,, M.Sc., Ph.D., SpM. and Dr. dr. Tatit Nurseta,, SpOG.(K).Onk. (2019) Regangan Ligamentum Sakrouterina Saat Inpartu Meningkatkan Kejadian Prolap Uteri Pasca Persalinan Melalui Jalur Integrin. Doktor thesis, Universitas Brawijaya.

Abstract

Pendahuluan. Patomekanisme terjadinya prolap organ panggul sampai saat ini belum jelas. Kejadian prolap organ panggul dihubungkan dengan kelainan genetik pada elastin. Prolap organ panggul juga berhubungan dengan penurunan elastin dan TIMP 1 serta peningkatan MMP-9, MMP-2. Persalinan adalah merupakan faktor resiko utama terjadinya prolap organ panggul. Saat inpartu, ligamentum sakrouterina teregang yang mengakibatkan prolaps uteri pasca persalinan. Regangan mekanik pada jaringan penyangga dasar panggul saat persalinan menyebabkan regangan pada matriks estraseluler jaringan penyangga dasar panggul. Regangan pada matriks ekstraseluler ini akan dirasakan oleh integrin. Sinyal dari integrin ini akan diteruskan untuk memicu sinyal dengan mengaktifkan IkB dan MAPK yang akhirnya akan meningkatkan aktifitas faktor transkripsi NFkB. Akibatnya terjadi peningkatan MMP-9 dan MMP 2, penurunan TIMP dan ini akan meningkatkan degradasi elastin. Keadaan penurunan elastin ini berpengaruh terhadap kejadian prolap uteri. Sampai saat ini belum ada penelitian yang membuktikan bahwa terjadi perubahan molekuler pada prolap uteri paska salin dengan serangkaian dugaan seperti tersebut diatas. Tujuan. Penelitian ini bertujuan untuk membuktikan bahwa inpartu meningkatkan kejadian prolap uteri pasca persalinan melalui jalur integrinα2 (dengan penurunan ekspresi IkB-β, peningkatan aktifitas p38α, peningkatan ekspresi nuklear p50 NFkB, peningkatan MMP-9, peningkatan MMP-2, penurunan TIMP-1 dan penurunan elastin) pada ligamentum sakrouterina Metode. Penelitian ini dilakukan dengan cara mengumpulkan sampel secara consecutive sampling dari biopsi ligamentum sakrouterina ibu hamil aterm yang menjalani operasi seksio sesarea karena persalinan macet pada kala 1dan kala 2 persalinan. Sebagai kontrol diambil sampel biopsi ligamentum sakrouterina dari ibu hamil aterm yang belum masuk fase persalinan yang menjalani operasi seksio sesarea elektif. Metode pada penelitian ini adalah cross sectional. Sampel ligamentum sakrouterina dilakukan beberapa perlakuan. Dilakukan pemeriksaan immunohistokimia untuk melihat ekspresi integrinα2, ekspresi IkB-β, aktifitas p38α. Ekspresi nuklear p50 NFkB diamati dengan pemeriksaan mikroskop confocal. Pemeriksaan ekspresi MMP-9, MMP-2, TIMP-1 dan elastin juga dengan imunohistokimia. Hasil. Terjadi peningkatan ekspresi integrin∝2, ekspresi IkB-β, aktifitas p38 , ekspresi nuklear p50NFkB, ekspresi MMP-9, ekspresi MMP-2 pada ligamentum sakrouterina pasca persalinan, terjadi penurunan ekspresi , TIMP-1, elastin pada ligamentum sakrouterina pasca persalinan. Dibuktikan pula bahwa terdapat hubungan antara penurunan elastin ligamentum sakrouterina dengan kejadian prolap uteri pasca persalinan. Persalinan meningkatkan kejadian prolap uteri pasca persalinan melalui jalur integrin∝2 (dengan peningkatan ekspresi IkB-β, peningkatan aktifitas p38 , peningkatan ekspresi nuclear p50NFkB, peningkatan ekspresi MMP-9, peningkatan ekspresi MMP-2, penurunan ekspresi TIMP-1 dan penurunan ekspresi elastin) pada ligamentum sakrouterina.

English Abstract

Introduction. The pathomechanism of pelvic organ prolapse to date is unclear. Pelvic organ prolapse events are associated with genetic abnormalities in elastin. Pelvic organ prolapse is also associated with decreased elastin and TIMP 1 and increased MMP-9, MMP-2. Labor is a major risk factor for pelvic organ prolapse. In Inpartu, there is strectch of of sacrouterine ligament which caused post partum uterine prolaps. Mechanical strain on the pelvic floor tissue during labor causes a strain on the extracellular matrix of the pelvic floor tissue. This strain on the extracellular matrix will be felt by integrins. The signal from this integrin will be forwarded to trigger the signal by activating IkB and MAPK which will ultimately increase the activity of the NFkB transcription factor. As a result there is an increase in MMP-9, MMP 2 and this will increase the degradation of elastin and TIMP. The decrease in elastin affects the incidence of uterine prolapse. Until now there have been no studies that prove that molecular changes in uterine prolapse occur after copying with a series of predictions as mentioned above. Aim. This study aims to prove that inpartu increase the incidence of postpartum uterine prolapse through the integrinα2 pathway (with a decrease in IkB-β expression, increased p38α activity, increased nuclear expression p50 NFkB, increased MMP-9, increased MMP-2, decreased TIMP -1 and decrease in elastin) in the sacrouterine ligament Method. This study was conducted by collecting samples by consecutive sampling from sacrouterine ligament biopsy from atterm pregnant women who underwent cesarean section surgery because labor was delayed at 1 and 2 times in labor. As a control, a sample of sacrouterina ligament biopsy was taken from pregnant women who had not entered the labor phase who underwent elective cesarean section surgery. The method in this study is cross sectional. Sacrouterine ligament samples were treated in several ways. Immunohistochemical examination was performed to see integrinα2 expression, IkB-β expression, p38α activity. Nuclear p50 NFkB expression was observed by confocal microscope examination. Examination of MMP-9, MMP-2, TIMP-1 and elastin expression was also done by immunohistochemistry. Results. There was an increase in integrin∝2, IkB-β, p38∝ activity, nuclear p50NFkB, MMP-9, MMP-2 in the postpartum ligament, a decrease in the expression of TIMP-1 and elastin in the post-delivery sacrouterine ligament. It was also proven that there was a relationship between a decrease in sacrouterine ligament elastin and the incidence of postpartum uterine prolapse. Labor increases the incidence of postpartum uterine prolapse through the integrin2 pathway (with an increase in IkB-β expression, increased p38∝ activity, increased nuclear p50NFkB expression, increased MMP-9 expression, increased MMP-2 expression, decreased TIMP-1 expression and decreased expression elastin) in the sacrouterine ligament.

Item Type:	Thesis (Doktor)
Identification Number:	DIS/612.63/RAH/r/2019/061902118
Subjects:	600 Technology (Applied sciences) > 612 Human Physiology > 612.6 Reproduction, development, maturation > 612.63 Pregnancy and childbirth
Divisions:	S2/S3 > Doktor Ilmu Kedokteran, Fakultas Kedokteran
Depositing User:	Sugeng Moelyono
Date Deposited:	11 Oct 2022 01:16
Last Modified:	11 Oct 2022 01:16
URI:	http://repository.ub.ac.id/id/eprint/195501

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