Rachmad, Yoga Tribakti (2018) Bioaktif Peptida Csn1s2 Sebagai Imunomodulator Dan Inhibitor Stres Oksidatif Untuk Perbaikan Abnormalitas Aorta Tikus Putih (Rattus Novergicus) Model Diabetes Melitus Tipe 2. Magister thesis, Universitas Brawijaya.
Abstract
Diabetes Mellitus Tipe 2 (DMT2) merupakan penyakit degeneratif yang disebabkan adanya penurunan jumah insulin dan/atau resistensi insulin. Dampak yang ditumbulkan mengarah pada kondisi patologis karena adanya abnormalitas metabolisme yang terjadi. Salah satu jaringan yang terdampak ialah aorta, abnormalitas di jaringan aorta akan mengarah pada kondisi atherosklerosis. Tujuan penelitian ini adalah menganalisis Peranan Protein CSN1S2 dari susu kambing Peranakan Ettawa terhadap abnormalitas pada jaringan aorta berdasarkan tingkat ekspresi protein Cyclooxygenase, kondisi inflamasi, VEGF, VCAM-1, sebagai indikasi kerusakan jaringan aorta tikus model (Rattus novergicus) sebagai dampak dari Diabetes Melitus tipe 2. Sebanyak 24 ekor tikus pada penelitian ini dibagi menjadi 8 kelompok dengan 3 kali ulangan terdiri atas; kontrol (C), normal dengan pemberian CSN1S2 dengan dosis 375mg (CM375), 750mg (CM750), dan 1500mg (CM1500) /kg BB tikus, kelompok model diabetes mellitus tipe 2 (DM), diabetes dengan pemberian CSN1S2 dengan dosis 375mg (DM375), 750mg (DM750), dan 1500mg (DM1500) /kg BB. Pembentukan hewan model DMT2 dilakukan dengan diet pakan tinggi kolesterol dilanjutkan dengan injeksi Streptozotozin dosis 25 mg/kg BB hingga mengalami diabetes (kadar glukosa darah >200 mg/dl), dilanjutkan dengan perlakuan protein CSN1S2 sesuai dosis selama 28 hari. Tikus model dibedah dan jaringan target disimpan untuk di analisis. Analisis dilaksanakan dengan metode, histopatologi pewarnaan HE diamati dengan mikroskop Olympus BX-53 software CellSense, western bloting dikuantifikasi menggunakan software QuantityOne. Hasil yang diperoleh dianalisis secara statistik One way ANOVA menggunakan software SPSS 16.0. Hasil observasi parameter penelitian menunjukkan adanya kerusakan jaringan aorta tikus model DMT2 yang terdiri atas perubahan kondisi histologi berupa lepasnya sel-sel endotelium (65,66±23,86c), peningkatan makrofag (319,00±17,52e), pembentukan sel busa (139,00±19c), disertai peningkatan kadar ekspresi protein COX-2 (0.742±0.09 INT/mm2), VCAM-1 (0.3142 + 0.04 INT/mm2), respons imun peningkatan ekspresi IL-17 (0.701+0.04 INT/mm2) dibandingkan kondisi normal. Pemberian bioaktif peptida CSN1S2 dari susu segar kambing PE pada kelompok tikus model DMT2 berperan dalam menekan ekspresi COX-2 [DM375 (0.394±0.11 INT/mm2), DM750 (0.313±0.025 INT/mm2), (0.283±0.03 INT/mm2)] pada jaringan aorta . Pemberian bioaktif peptida CSN1S2 dari susu segar kambing PE berpengaruh terhadap kondisi inflamasi pada jaringan aorta tikus model DMT2 dengan kondisi penurunan ekspresi sitokin IL-17 [DM375 (0.45±0.05 INT/mm2), DM750 (0.303+0.04 INT/mm2), DM1500 (0.299 + 0.05 INT/mm2)] yang ditunjang dengan peningkatan ekspresi IL-10 [DM375 (0.405±0.07 INT/mm2), DM750 (0.662+0.08 INT/mm2), DM1500 (0.662+0.08 INT/mm2)] sebagai indikasi perbaikan jaringan. Pemberian bioaktif peptida CSN1S2 dari susu segar kambing PE pada tikus model DMT2 menyebabkan peningkatan ekspresi VEGF [DM375 (0.5841 + 0.07 INT/mm2), DM750 (0.4932 + 0.09 INT/mm2), DM1500 (0.3945 + 0.03 INT/mm2)] sebagai indikasi kembalinya permeabilitas jaringan aorta dan disertai dengan penurunan kadar VCAM-1[DM375 (0.3952 + 0.09 INT/mm2), DM750 (0.4051 + 0.04 INT/mm2), DM1500 (0.43820 + 0.03 INT/mm2)] sebagai indikasi penurunan senyawa molekul adhesi terhadap sel imun pada sel-sel endotel. Pemberian bioaktif peptida CSN1S2 dari susu segar kambing PE berpengaruh terhadap kondisi histologi jaringan aorta tikus model DMT2 dalam bentuk penurunan jumlah makrofag [(DM375 120,00±11,53d) (DM75059,66±12,05c), (DM1500 30,00±11,4b)] yang mengalami infiltrasi pada lapisan dinding aorta diserta penurunan terbentuknya sel busa pada lapisan dinding aorta [(DM375 39,00±9b), DM750 9,667±2,08a), (DM1500 8,333±4,16a)]. Penelitian yang telah dilaksanakan mengindikasikan bahwa protein CSN1S2 memiliki peranan dalam menekan produksi COX-2 pada aorta tikus model DMT2, tidak berpengaruh terhadap ekspresi COX-1, meningkatkan produksi IL-10, menekan produksi IL-17, meningkatkan ekspresi protein VEGF, menekan produksi VCAM-1 di jaringan aorta tikus pada kondisi DM
English Abstract
Diabetes Mellitus Type 2 (DMT2) is a degenerative disease caused by a decrease insulin production and/or insulin resistance. The Impacts in further condition leading to pathological conditions and metabolic abnormalities. One of the affected tissues is aorta, abnormalities in the aortic tissue will lead to atherosclerotic. The aim of this study was to analyze the role of Protein CSN1S2 from Ettawa Bread milk against abnormalities in aortic tissue based on CYL expression, inflammatory condition, VEGF, VCAM-1, as an indication of aortic tissue damage rat (Rattus novergicus) as the effect of type 2 Diabetes mellitus. The 24th rats in this study were divided into 8 groups with 3 repetitions consisting of; control (C), normal treated by CSN1S2 at doses of 375mg/kg BW (CM375), 750mg/kg BW (CM750), and 1500mg.kg BW (CM1500), Rat model type 2 diabetes mellitus (DM), diabetes rat treated by CSN1S2 at a dose of 375mg/kg BW (DM375), 750mg/BW (DM750), and 1500mg/BW (DM1500). Animal model of T2DM was performed with a diet high in cholesterol followed by injection of Streptozotozin dose 25 mg/kg BW until diabetic (blood glucose> 200 mg/dl), followed by treatment of protein CSN1S2 for 28 days. Animals model were dissected and tissue was stored for analysis. The analysis was performed by the histopathological method of HE staining observed by microscope Olympus BX-53 and software CellSense. The western blotting protein quantified analyzed by QuantityOne software. The data results were analyzed by One Way ANOVA statistic using SPSS 16.0 software. In rat model T2DM, of the study showed that there was damage of aortic tissue which consisted of changes in histology condition such as discontinued-endothelial cells (65,66 ± 23,86c), increased number of macrophage (319,00 ± 17,52e) and foam cells formation (139.00 ± 19c), along by elevated levels of COX-2 protein expression (0.742 ± 0.09 INT / mm2), VCAM-1 (0.3142 + 0.04 INT / mm2), and increased of immune responses expression IL -17 (0.701 + 0.04 INT / mm2) compared to all group. The bioactive peptide CSN1S2 from Ettawa goat milk in DMT2 model rat was in suppressing COX-2 expression [DM375 (0.394 ± 0.11 INT / mm2), DM750 (0.313 ± 0.025 INT / mm2), (0.283 ± 0.03 INT / mm2) ] in the aortic tissue. Administration of CSN1S2 bioactives peptide from Ettawa goat milk, affects inflammatory expression level in the aortic tissue of rat model DMT2 under conditions of decreased expression of IL-17 cytokines [DM375 (0.45 ± 0.05 INT / mm2), DM750 (0.303 + 0.04 INT / mm2), DM1500 0.299 + 0.05 INT / mm2)] supported by increased expression of IL-10 [DM375 (0.405 ± 0.07 INT / mm2), DM750 (0.662 + 0.08 INT / mm2), DM1500 (0.662 + 0.08 INT / mm2)] as an indication of improvement. The bioactive peptide CSN1S2 from Ettawa goat milk on T2DM model caused increased VEGF expression [DM350 (0.5841 + 0.07 INT / mm2), DM750 (0.4932 + 0.09 INT / mm2), DM1500 (0.3945 + 0.03 INT / mm2)] for indication of permeability aortic tissue. Decreased levels of VCAM-1 [DM350 (0.3952 + 0.09 INT / mm2), DM750 (0.4051 + 0.04 INT / mm2), DM1500 (0.43820 + 0.03 INT / mm2)] as an indication of decrease in adhesion molecule compound against immune cells in endothelial cells. Giving bioactive peptide CSN1S2 from fresh goat milk of PE has an effect on histology condition of aortic tissue of mouse model of DMT2 in the form of decreasing number of macrophages [(DM375 120,00 ± 11,53d) (DM75059,66 ± 12,05c), (DM1500 30,00 ± 11.4 b)] undergoing infiltration in the aortic wall layer as well as decreased formation of foam cells in the aortic wall layer [(DM375 39,00 ± 9b), DM750 9,667 ± 2.08a), (DM1500 8,333 ± 4,16a)]. The experimental results indicated that the CSN1S2 protein have role function as suppressed COX-2 and VCAM-1 production in the aortic mouse model DMT2, had no effect on COX-1 expression, increased IL-10 production, suppressed IL-17 production, increased VEGF protein expression in tissue rat aorta under DM conditions
Other obstract
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| Item Type: | Thesis (Magister) |
|---|---|
| Identification Number: | TES/616.462/RAC/b/2018/041802362 |
| Uncontrolled Keywords: | DIABETES, PEPTIDES, ENZYME INHIBITORS, OXIDATIVE STRESS |
| Subjects: | 600 Technology (Applied sciences) > 616 Diseases > 616.4 Diseases of endocrine, hematopoietic, lymphatic, glandular system; diseases of male breast > 616.46 Diseases of islands of Langerhans > 616.462 Diabetes mellitus |
| Divisions: | S2/S3 > Magister Biologi, Fakultas MIPA |
| Depositing User: | Budi Wahyono Wahyono |
| Date Deposited: | 12 Aug 2019 08:20 |
| Last Modified: | 12 Aug 2019 08:20 |
| URI: | http://repository.ub.ac.id/id/eprint/171283 |
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