i

KARYA TULIS AKHIR

PENGARUH EKSTRAK KUNYIT (Curcuma longa) TERHADAP

EKSPRESI SEL MAST KONJUNGTIVA TIKUS (Rattus

novergicus) MODEL ALERGI YANG DIINDUKSI

OVALBUMIN

Oleh :

RIZKYA ARINI SUROYA FAYS

201310330311075

FAKULTAS KEDOKTERAN

UNIVERSITAS MUHAMMADIYAH MALANG

2017

ii

iii

KATA PENGANTAR

Alhamdulillah puji syukur kehadirat Allah SWT., Tuhan semesta alam,

Yang Maha Pengasih lagi Maha Penyayang, Yang Maha Pemberi semua nikmat,

kebaikan, dan kekuatan selama proses pelaksanaan, Penulis Skenario Terbaik

Yang Maha Menyimpan rahasia hikmah di balik semua peristiwa, Yang Maha

Memudahkan, dan atas karunia-Nya penulisan tugas akhir ini dapat selesai dengan

baik. Hanya kepada-Nya pujian layak disandangkan, memohon pertolongan dan

memohon ampunan. Dan kepada-Nya tempat berlindung dari kejahatan jiwa dan

keburukan perbuatan.

Sholawat serta salam tak lupa mari kita haturkan kepada Nabiyullah, Nabi

akhir zaman, Rasulullah Muhammad SAW., beserta keluarganya, para

sahabatnya, dan orang-orang yang mengikutinya hingga hari kiamat, semoga kita

semua mendapat syafa’atnya di akhirat kelak. Penelitian tugas akhir ini berjudul

“Pengaruh Ekstrak Kunyit (Curcuma longa) Terhadap Ekspresi Sel Mast

Konjungtiva Tikus (Rattus novergicus) Model Alergi Yang Diinduksi

Ovalbumin”, diajukan untuk memenuhi persyaratan Pendidikan Sarjana Fakultas

Kedokteran Universitas Muhammadiyah Malang.

Pada kesempatan ini, penulis ingin menyampaikan terimakasih kepada :

1. dr. Irma Suswati, M.Kes, selaku Dekan Fakultas Kedokteran Universitas

Muhammadiyah Malang atas ilmu dan bimbingannya selama di Fakultas

Kedokteran UMM.

iv

2. Wakil Dekan Fakultas Kedokteran Universitas Muhammadiyah Malang

yang telah memberikan saya dosen pembimbing dan penguji yang begitu

arif dan sabar.

3. dr. Alfa Sylvestris, Sp.M, selaku pembimbing 1, atas kesabaran, kebaikan

hati, serta kesediaan dalam meluangkan waktu dalam membimbing hingga

dapat menyelesaikan penelitian ini dengan baik.

4. dr. Gita Sekar Prihanti, MPD.Ked, selaku pembimbing 2, atas kesabaran,

kebaikan hati, serta kesediaan dalam meluangkan waktu dalam

membimbing hingga dapat menyelesaikan penelitian ini dengan baik.

5. dr. Annisa’ Hasanah, M.Si, selaku dosen penguji, atas kesediaan waktu

dan penyampaian ilmu yang sangat bermanfaat bagi masa depan para

mahasiswa FK UMM.

Penulis menyadari bahwa tugas akhir ini masih jauh dari kata sempurna.

Oleh karena itu, penulis sangat mengharapkan saran dan masukan yang

membangun. Dengan mengharapkan Keridhaan-Nya, semoga karya tulis ini dapat

menambah wawasan keilmuan dan bermanfaat bagi semua pihak.

Wassalamualaikum Warahmatullahi Wabarakatuh.

Malang, 13 Februari 2017

Penulis

v

DAFTAR ISI

Halaman

HALAMAN JUDUL DEPAN ........................................................................ ii

LEMBAR PENGESAHAN ........................................................................... iii

PERNYATAAN ORISINILITAS ................................................................ iv

LEMBAR PENGUJIAN ................................................................................ v

KATA PENGANTAR ................................................................................... vi

UCAPAN TERIMA KASIH ....................................................................... viii

ABSTRAK ....................................................................................................... x

DAFTAR ISI ................................................................................................. xii

DAFTAR TABEL ......................................................................................... xv

DAFTAR GAMBAR ................................................................................... xvi

DAFTAR SINGKATAN ............................................................................ xvii

DAFTAR LAMPIRAN ............................................................................. xviii

BAB 1 PENDAHULUAN

1.1 Latar Belakang .............................................................................. 1

1.2 Rumusan Masalah ......................................................................... 2

1.3 Tujuan Penelitian ........................................................................... 2

1.3.1 Tujuan Umum .................................................................... 2

1.3.2 Tujuan Khusus ................................................................... 2

1.4 Manfaat Penelitian ......................................................................... 3

1.4.1 Manfaat Klinis.................................................................... 3

1.4.2 Manfaat Akademis ............................................................. 3

1.4.3 Manfaat Masyarakat ........................................................... 3

BAB 2 TINJAUAN PUSTAKA

2.1 Konjungtiva .................................................................................... 4

2.1.1. Anatomi Konjungtiva ........................................................ 4

2.1.2. Histologi Konjungtiva ....................................................... 5

2.1.3. Vaskularisasi dan inervasi ................................................. 6

2.1.4. Perbandingan konjungtiva manusia dan tikus ................... 7

2.2. Konjungtivitis Alergi ..................................................................... 7

2.2.1. Definisi ............................................................................. 7

vi

2.2.2. Epidemiologi ..................................................................... 8

2.2.3. Etiologi ............................................................................ 10

2.2.4. Klasifikasi konjungtivitis alergi ...................................... 10

2.2.5. Patofisiologi konjungtivitis alergi ................................... 14

2.2.6. Terapi .............................................................................. 15

2.3. Respon Sel Mast pada Konjungtivitis Alergi .............................. 17

2.4. Ekstrak Kunyit ............................................................................. 18

2.4.1. Sifat Fisik ........................................................................ 18

2.4.2. Kandungan ekstrak kunyit .............................................. 20

2.4.3. Manfaat ekstrak kunyit.................................................... 21

2.4.4. Toksisitas ........................................................................ 21

2.4.5. Kurkumin sebagai antialergi ........................................... 22

2.4.6. Kurkumin terhadap ekspresi sel mast ............................. 22

2.5. Ovalbumin ................................................................................... 23

2.5.1. Definisi ............................................................................ 23

2.5.2. Ovalbumin sebagai alergen ............................................. 24

2.6. Aluminium Hidroksida (ALUM) ................................................ 25

2.6.1. Definisi ............................................................................ 25

2.6.2. Ovalbumin dan Aluminium Hidroksida dalam reaksi imun

................................................................................................... 25

BAB 3 KERANGKA KONSEPTUAL DAN HIPOTESIS PENELITIAN

3.1. Kerangka Konseptual Penelitian ................................................. 26

3.2. Hipotesis Penelitian ..................................................................... 27

BAB 4 METODE PENELITIAN

4.1. Jenis dan Rancangan Penelitian................................................... 28

4.2. Tempat dan Waktu Penelitian ..................................................... 28

4.3. Populasi dan Sampel Penelitian................................................... 28

4.3.1. Populasi ........................................................................... 28

4.3.2. Besar Sampel................................................................... 29

4.4. Teknik Sampling ......................................................................... 30

4.5. Kelompok Perlakuan ................................................................... 30

4.6. Variabel Penelitian ...................................................................... 31

vii

4.7. Definisi Operasional .................................................................... 31

4.8. Alat dan Bahan Penelitian ........................................................... 35

4.9. Prosedur Penelitian ...................................................................... 36

4.9.1. Aklimatisasi .................................................................... 36

4.9.2. Pengelompokan hewan coba ........................................... 37

4.9.3. Pembuatan ekstrak kunyit ............................................... 37

4.9.4. Penghitungan Dosis......................................................... 38

4.9.5. Proses Anastesi dan Pengambilan jaringan konjungtiva. 40

4.9.6. Perlakuan terhadap hewan coba setelah dibedah ............ 41

4.10. Alur Penelitian ........................................................................... 41

4.11. Analisis Statistik ........................................................................ 42

BAB 5 HASIL PENELITIAN DAN ANALISIS DATA

5.1 Hasil Penelitian ............................................................................. 44

5.2 Analisis Data ................................................................................ 46

5.2.1. Normalitas Data dan Homogenitas Data ......................... 46

5.2.2. Analisis One – Way ANOVA ......................................... 46

5.2.3. Uji Post Hoc (Bonferroni) ............................................... 47

5.2.4. Uji Korelasi Pearson dan Regresi Linier ........................ 47

BAB 6 PEMBAHASAN ............................................................................... 50

BAB 7 KESIMPULAN DAN SARAN

7.1 Kesimpulan ................................................................................... 55

7.2 Saran ............................................................................................. 55

DAFTAR PUSTAKA ………………………………………………….. ....56

LAMPIRAN...................................................................................................60

viii

DAFTAR LAMPIRAN

Lampiran Halaman

1. Analisis Data....................................................................................................60

2. Surat Komisi Etik.............................................................................................66

3. Surat Keterangan Penelitian.............................................................................67

4. Surat Determinasi Tanaman kunyit..................................................................68

5. Surat Pembuatan Ekstrak Kunyit......................................................................69

6. Surat Pembacaan PA........................................................................................70

7. Surat Komisi Ilmiah.........................................................................................71

8. Dokumentasi....................................................................................................72

9. Kartu Konsultasi Tugas Akhir.........................................................................74

ix

DAFTAR PUSTAKA

Abdou AM, Kim M, Sato K, 2013, Functional Proteins and Peptides of Hen’s

Egg Origin, Bioactive Food Peptides in Health and Disease, pp. 115-144.

Abidi A, Gupta S, Agarwal M et al, 2014, Evaluation of Efficacy of Curcumin as

an Add-on therapy in Patients of Bronchial Asthma, Journal of Clinical

and Diagnostic Research, Vol 8(8), pp. 19-24.

Alena F, Jameel AA, Ivana K et al, 2014, Pigmented Epibulbar Lesions:

Overview. Journal of Pigmentary Disorders, Vol 1(3), pp. 1-8.

Alexandru I, 2011, Experimental use of animals in research, Balneo-Research

Journal, Vol.2, no.1, pp.65-69.

Alleoni ACC, 2006, Albumen Protein and Functional Properties of Gelation and

Foaming, Proteins of Albumen functional Properties, Vol 63, pp. 291-298.

American Academy of Ophthalmology, 2013, Guidelines:Conjunctivitis. San

Fransisco: American Academy of Ophthalmology.

Arts JWM, Kramer K, Arndt SS et al, 2012, The Impact of Transportation on

Physiological and Behavioral Parameters in Wistar Rats: Implications for

Acclimatization Period, pp. 1-17.

Azari AA, Barney NP, 2013, Conjunctivitis: A Systematic Review of Diagnosis

and Treatment, JAMA Clinical Review & Education, Vol 310(16), pp.

1721 - 1729.

Bagchi A, 2012, Extraction of Curcumin, Journal of Environmental Science,

Toxicology and Food Technology, Vol 1(3), pp. 1-16.

Baratawidjaja KG, Rengganis I, 2013, Sel-Sel Sistem Imun Nonspesifik,

Imunologi Dasar, 10 edn, Fakultas Kedokteran Universitas Indonesia,

Jakarta.

Basnet P, Basnet NS, 2011, Curcumin: An Anti-Inflammatory Molecule from a

Curry Spice on the Path to Cancer Treatment, Molecules, Vol 16, pp.

4567-4598.

Bonini S, Sgrulletta R, Coassin M et al, 2009, Allergic Conjunctivitis: Update on

Its Pathophysiology and Perspectives for Future Treatment, Allergy

Frontiers: Clinical Manifestations, pp. 26 - 48.

Chen J et al, 2016, Topical Application of Interleukin-28A Attenuates Allergic

Conjunctivitis in an Ovalbumin-Induced Mouse Model, Investigative

Ophthalmology & Visual Science, Vol 57(2), pp. 604-610.

x

Cordova C, Gutierrez B, Garcia CM et al, 2014, Oleanolic Acid Controls Allergic

and Inflammatory Responses in Experimental Allergic Conjuntivitis, Plos

One, Vol 9(4), pp. 1-11.

Eroschenko VP, 2010, difiore's Atlas of Histology with Functional Correlations,

11 edn, EGC, USA.

Eva PR, Whitcher JP, 2009, Konjungtiva, In : Garcia-Ferrer FJ, Schwab IR,

Shetlar DJ (eds). Vaughan & Asbury’s General Ophthalmology, 17 edn,

EGC, USA, pp. 97-124.

F, Vianello, 2006, Levels of OVA secreted in CM from B16/OVA.MSCV and

B16/OVA.CXCL12 cells cultured for 24 h were also measured by ELISA.

J. Immunol., Vol 176, pp. 2902-2914.

Fathoni et al, 2016, Pengaruh Influsi Terhadap Jumlah Sel Mast Peritoneum

Tikus, Berkala Kedokteran, Vol 12 (1), pp. 411-47.

Hartati SY, Balittro, 2013, Khasiat Kunyit sebagai Obat Tradisional dan Manfaat

Lainnya. Warta Penelitian dan Pengembangan Tanaman Industri, Vol

19(2), pp. 5-9.

Hazarika AK, 2015, Benefits and Risk of Topical Corticosteroids in the

Management of Ocular Inflammation, SMU Medical Journal, Vol 2, pp.

295-305.

Ibrahim MN, Widjajanto E, Permatasri N et al, 2009, Karboksimetil Kitosan

Menurunkan Degranulasi Mast Cell yang Diinduksi Oleh Ovalbumin.

Jurnal Kedokteran Brawijaya, Vol 25, pp. 6-9.

INSA (Indian National Science academy), 2000, Guideline For Care and Use Of

Animals In Scientific Research, Bengal Offset Works, New Delhi, pp. 14-

15.

Ishida W, Fukuda K, Kajisako M et al, 2010, Conjunctival Macrophages Act As

Antigen-Presenting Cells in the Conjunctiva during the Development of

Experimental Allergic Conjunctivitis, Molecular Vision, Vol 16, pp. 1280-

1285.

Jurenka JS, 2009, Anti-inflammatory Properties of Curcumin, a Major

Constituent of Curcuma longa, A Review of Preclinical and Clinical

Research, Alternative Medicine Review, Vol 14(2), pp. 141-153.

Katelaris CH, 2011, Ocular allergy in the Asia Pacific region, Asia Pacific

Association of Allergy, Asthma and Clinical Immunology, Vol 1, pp.108-

114.

xi

Kato et al, 2014, Nasal Sensitization with Ragweed Pollen Induces Local Allergic

Rhinitis Like Symptoms in Mice, PLOS ONE, Vol 9(8), pp. 1-11.

Kinney SRM, Carlson L, Dolansky JS et al, 2015, Curcumin Ingestion Inhibits

Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of

Food Allergy. PLOS ONE, Vol 10(7), pp. 1-20.

Klintworth GK, Cummings TJ, 2007, Normal Eye and Ocular Adnexa. In

Histology for Pathologist.

Kool M et al, 2008, Cutting Edge: Alum Adjuvant Stimulates Inflammatory

Dendritic Cells through Activation of the NALP3 Inflammasome, J

Immunol, Vol 181(6), pp.3755-9.

Krup V, Prakash LH, Harini A, 2013, Pharmacological Activities of Turmeric

(Curcuma longa linn): A Review. Homeopathy & Ayurvedic Medicine, Vol

2(4), pp. 1-4.

Kuehnel W, 2003, Citology, Histology, and Microscopic Anatomy, 4 edn, Thieme,

New York.

Kurniawan, 2009, Efek Epigallocatechin-3-Galatte (EGCE) Topikal Terhadap

Sebukan Neutrofil Konjungtivitis Alergi, Fakultas Kedokteran Universitas

Diponegoro Semarang, pp. 1-71.

La Rosa M, Lionetti E, Reibaldi M et al, 2013, Allergic Conjunctivitis: A

Comprehensive Review of the Literature, Italian Journal of Pediatrics,

Vol 39(18). pp. 1-8.

Lopez HM, Melendez CAP, Flores AC et al, 2011, Epidemiological Aspects of

Infectious Conjunctivitis, Conjunctivitis - A Complex and Multifaceted

Disorder, pp. 1-18.

Mello CB, Ramos L, Gimenes AD et al, 2015, Immunomodulatory Effects of

Galectin-1 on an Ig-EMediated Allergic Conjunctivitis Model,

Investigative Ophthalmology and Visual Science, Vol 56, pp. 693-704.

Moehariadi Hariwati, Yasmine, 2012, Perbandingan Konsentrasi IgE Air Mata

Penderita Alergi Okuli dengan Pemberian Pemirolast Potassium 0,1% dan

Sodium Cromoglycate 4%, Jurnal Kedokteran Brawijaya, Vol. 27(2),

pp.111-114.

Nasri H, Sahinfard N, Rafieian M et al, 2014, Turmeric: A spice with

multifunctional medicinal properties, Journal of HerbMed Pharmacology,

Vol 3(1), pp. 5-8.

xii

Pelikan Z, 2013, Mediator Profiles in Tears During the Conjunctival Response

Induced by Allergic Reaction in the Nasal Mucosa, Molecular Vision, Vol

19, pp. 1453-1470.

Reber, L. L., F. Daubeuf, M. Plantinga et al, 2012, A Dissociated Glucocorticoid

Receptor Modulator Reduces Airway Hyperresponsiveness and

Inflammation an a Mouse Model of Asthma, J Immunol, Vol 188(7),

pp.3478-3487.

SEPA (Scottish Environmental Protection Agency), 2009, Burial of Small

Quantities of Rodent Carcasses Poisoned on Farmland, National West

Policy unit, pp.1-2.

Shancez MC, Parra BP, Matheu V et al, 2011, Allergic Conjunctivitis, J Investig

Allergol Clin Immunol, Vol 21, pp. 1 - 19.

Singletary K, 2010, Turmeric An Overview of Potential Health Benefits, Nutrition

Today, Vol 45, pp. 216-225.

So-Hyang C, Seong Hyun C, Jin AC et al, 2012, Curcumin suppresses ovalbumin-

induced allergic conjunctivitis, Molecular Vision, Vol 18, pp.1966-1972.

Strobehn A, Ward M, Kitzmann A, 2013, Atopic Keratoconjunctivitis, Eye

Rounds, pp.1-5.

Subijanto A, Diding HP, 2006, Pengaruh Minyak Biji Jinten Hitam (Nigella

Sativa L.) terhadap Derajat Inflamasi Saluran Nafas. Majalah Kedokteran

Indonesia, Vol 58, pp. 200-204.

Subhashini, Chauhan PS, Kumari S et al, 2013, Curcumin inhibits compound

48/80 induced systemic anaphylaxis, American Journal of Life Sciences,

Vol1(4), pp. 165-170.

Vichyanond P, Pacharn P, Pleyer U et al, 2013, Vernal keratoconjunctivitis: A

Severe Allergic Eye Disease with Remodeling Changes, Pediatric Allergy

and Immunology, pp.1-9.