1 / 23

Oleh: Nydya Parahita (0910710011)

Pemaparan Saliva Manusia terhadap Aktivasi Matrix Metalloproteinase 9 (MMP-9) pada Peripheral Blood Mononuclear Cells (PBMCs) Penderita Infark Miokard Akut (IMA) secara I n Vitro. Oleh: Nydya Parahita (0910710011). Pembimbing: Dr. d r. I Ketut Gede Muliartha, SpPA

berget
Download Presentation

Oleh: Nydya Parahita (0910710011)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Pemaparan Saliva Manusia terhadap Aktivasi Matrix Metalloproteinase 9 (MMP-9) pada Peripheral Blood Mononuclear Cells (PBMCs) Penderita Infark Miokard Akut (IMA) secara In Vitro Oleh: Nydya Parahita (0910710011) Pembimbing: Dr. dr. I Ketut Gede Muliartha, SpPA Dr. dr. Retty Ratnawati, MSc Penguji: dr. Cholid Tri Tjahjono, MSc

  2. LatarBelakang WHO : 20% KEMATIAN DUNIA  ATEROSKELEROSIS, TERMASUK IMA. USA : >500.000 ORANG MENINGGAL  IMA IND : PENY. KARDIOVASKULAR MENINGKAT TIAP TAHUNNYA (Atinia, 2006) PerluPenanganan (Diagnosis&Terapi) Cepat, Tepat & Cermat • Kontra Indikasi • Efek Samping • Thrombositopenia • Perdarahan • Ulkus Lambung • Biaya SALIVA Histatin 5 menghambataktivasi MMP-9, yang berperandalampenebalantunikaintima & rupturnyaplak Dwivedi et. al., 2009 Gusman et. al., 2001 Newby, 2007

  3. Rumusan Masalah Apakah pemberian histatin-5 dalam saliva manusia pada Peripheral Blood Mononuclear Cells (PBMCs) penderita Infark Miokard Akut (IMA) dapat menurunkan aktivasi Matrix Metalloproteinase 9 (MMP-9) secara in vitro? Tujuan Penelitian Membuktikan bahwa pemberian histatin-5 dalam saliva manusia pada Peripheral Blood Mononuclear Cells (PBMCs) penderita Infark Miokard Akut (IMA) dapat menurunkan aktivasi Matrix Metalloproteinase 9 (MMP-9) secara in vitro.

  4. Patogenesis IMA Kumar et. al., 2003

  5. Diagnosis IMA 1. NYERI DADA khas > 20 menit 2. Perubahan EKG yang khas • 3. Peningkatan enzim 2 kali di atas normal: • CKMB • cTn • Mioglobin • Creatinine Kinase • Lactic Dehydrogenase Malinrungi, 2003, Alwi, 2006

  6. Terapi IMA Saat Ini • Bed rest • Oksigen • Mengurangi nyeri dada: morfin • Anti iskemia: nitrat, beta blocker • Fibrinolitik (STEMI): SK, tPA, retavase, TNKase • ACE-i (STEMI) • Anti platelet: aspirin, klopidogrel, antagonis GP IIb/IIIa • Anti koagulan: UFH, LMWH • Invasif: kateterisasi, revaskularisasi

  7. MMP-9 Visse dan Nagase, 2003

  8. MMP-9 pada Penderita IMA Stimulasi proliferasi sel otot polos pembuluh darah dan penebalan tunika intima (Uglowet. al., 2003, Dwivedi et. al., 2009, Tsaousiet. al., 2011). Degradasi fibrous cap dan menyebabkan ruptur plak aterosklerosis (Loftus et. al., 2000, Newby, 2007).

  9. Saliva • Disekresi kelenjar saliva mayor dan minor (0,5—1,5 L/hari). • Komponen anorganik: air, bikarbonat, fosfat, sodium, klorida, potasium. • Komponen organik: lipid, karbohidrat, protein. • Protein dalam saliva: cystatin, gustin, histatin, laktoferin, lisosim, mucin. Hashim, 2010, Fa’bi’an dan Ferjerdy, 2007

  10. Histatin-5 • Disekresi kelenjar saliva mayor (30—150 mcg/ml) (Wei, 2008). • Antifungal: C. albicans, C. glabrata, C. krusei, Saccharomyces cereviseae, Cryptococcus neoformans (Wunder et. al., 2004).

  11. Kerangka Konsep

  12. Metode Penelitian

  13. Hasil Penelitian dan Analisa Data Hasil Pengukuran Kadar MMP-9 di PBMCs

  14. Hasil Penelitian dan Analisa Data Hasil Pengukuran Kadar Histatin-5 di Saliva

  15. Hasil Penelitian dan Analisa Data Hasil PengukuranAktivasi MMP-9 SetelahDipapar Saliva

  16. Hasil Penelitian dan Analisa Data Keterangan: Biru : nilai p < 0,05 = terdapat perbedaan bermakna antara dua kelompok. * : nilai p > 0,05 = tidak terdapat perbedaan bermakna antara dua kelompok

  17. Konsentrasi MMP-9 MeningkatpadaPenderita IMA Loftus et. al., 2000 The concentration, production, and expression of MMP-9 is significantly higher in unstable carotid plaques. If this proves to be a causal relationship, MMP-9 may be a strong candidate for pharmacotherapy aimed at stabilizing plaques. Blankenberget. al., 2003 Plasma MMP-9 concentration was identified as a novel predictor of CV mortality in patients with coronary artery disease. Xuet. al., 2004 MMP-9 concentrations in plasma and monocyte supernatants from patients with AMI were significantly higher than in patients with UAP (p<0.05).

  18. Histatin-5 sebagaiZinc Chelating Agent Histatin-5 Rantai HEXXH Zinc chelating agent Zinc binding motif Inhibisi aktivasi enzim dependen zinc Grogan et. al., 2001, Gusman et. al., 2001, Sun et. al., 2009

  19. InhibisiAktivasi MMP-9 oleh Histatin-5 Histatin-5 Zn X Zn Zn Zn Zn

  20. DampakPenurunanAktivasi MMP-9 N-cadherin MMP-9 Beta-catenin nuclear Beta-cateninsignalling VSMC proliferation Type IV collagen degradation Stable plaque Loftus et. al., 2000, Newby, 2007, Uglowet. al., 2003, Dwivedi et. al., 2009, Tsaousiet. al., 2011

  21. Kesimpulan Pemberian saliva manusia yang mengandung histatin-5 pada PBMCs penderita IMA dapat menurunkanaktivasiMMP-9secarain vitro. Saran • Diperlukanpenelitianlebihlanjutmengenai : • Pengaplikasiansaliva pada darah penderita IMA terhadap penurunanaktivasiMMP-9secarain vivo. • Toksilogidanefeksampingdaripemberian saliva pada darah penderita IMA terhadap penurunanaktivasiMMP-9. • Dosisamanpemberian saliva pada darah penderita IMA terhadap penurunanaktivasiMMP-9 secara in vivo.

  22. Terimakasih

More Related