Monica, dr. Ervin and dr. Satrio Wibowo, M.Si., Med., Sp.A (K). and dr. Eko Sulistijono, Sp.A (K). (2020) Perbedaan Ekspresi TNF-α, IL- 6 dan Kadar Hemoglobin Pada Mencit Yang Diinduksi DSS Saja dan Yang Diberikan Vitamin D3”. Magister thesis, Universitas Brawijaya.
Abstract
Kolitis ulseratif merupakan bagian dari Inflammatory Bowel Disease yang ditandai dengan adanya lesi difus di kolon. Inflamasi kronis yang terjadi pada kolitis ulseratif disebabkan karena adanya ketidakseimbangan sistem imun pada usus sehingga adanya produksi berlebih dari sitokin-sitokin pro-inflamasi seperti TNF-α dan IL-6. Hal tersebut memperburuk kondisi peradangan pada usus serta turut berperan dalam manifestasi maupun komplikasi ekstraintestinal dari kolitis ulseratif yaitu anemia yang ditandai dengan penurunan kadar hemoglobin. Selain adanya ketidakseimbangan sistem imun, didapatkan juga defisiensi vitamin D pada sekitar 44% pasien kolitis ulseratif. Vitamin D3 merupakan bentuk aktif dari vitamin D yang tidak hanya berperan dalam remodeling tulang tapi juga dalam sistem imun. Vitamin D3 dapat berperan pada sistem imun innate dengan memproduksi berbagai antimikroba dan peningkatan pengenalan TLR-4, sedangkan pada sistem imun adaptif vitamin D3 akan menghambat Th1 sehingga menekan sitokin-sitokin pro-inflamasi serta menghambat jalur Nf-κB yang juga memperantarai aktivasi dari berbagai sitokin pro-inflamasi. Dextran Sulphate Sodium (DSS) merupakan zat yang bisa digunakan untuk menginduksi kolitis pada hewan coba. Dextran Sulphate Sodium (DSS) yang bersifat toksik terhadap kolon akan merusak barrier dari epitel kolon sehingga berbagai patogen dapat translokasi ke mukosa kolon dan mengaktifkan sistem imun terutama sitokin-sitokin pro- inflamasi yang semakin memperberat kerusakan kolon. Sistem scoring yang dapat digunakan untuk mengetahui efek kerusakan yang ditimbulkan akibat induksi DSS pada hewan coba yaitu Disease Activity Index (DAI) dan Mouse Colitis Histology Index (MCHI). Penelitian ini bertujuan untuk membuktikan efek pemberian vitamin D3 dapat menurunkan sitokin-sitokin pro-inflamasi seperti TNF-α dan IL-6 sehingga kerusakan kolon akibat DSS dan manifestasi ekstraintestinalnya dapat ditekan. Penelitian ini menggunakan hewan coba mencit jantan BALB/c sejumlah 24 ekor yang dibagi menjadi 4 kelompok secara acak. Kelompok kontrol negatif hanya diberikan aquadest, kelompok kontrol positif (model mencit kolitis) diberikan Dextran Sulphate Sodium 3% (DSS 3%) selama 7 hari, kelompok perlakuan I diberikan DSS 3% selama 7 hari kemudian diberikan vitamin D3 dengan dosis 0.2 μg/25gram/hari selama 7 hari, kelompok perlakuan II diberikan vitamin D3 dengan dosis 0.2 μg/25gram/hari selama 7 hari kemudian diberikan DSS 3 % selama 7 hari. Selama perlakuan dilakukan perhitungan skor Disease Activity Index (DAI) kemudian dibedah dan dicek Mouse Colitis Histology Index (MCHI), ekspresi TNF-α dan IL-6 serta kadar hemoglobin. Hasilnya dianalisis menggunakan Anova dan Post Hoc Tukey jika data terdistribusi normal dan homogen serta Kruskal Wallis dan Post Hoc Mann Whitney jika tidak data tidak terdistribusi normal dan homogen. Khusus untuk data skor DAI akan dianalisis menggunakan Friedman dan Wilcoxon. Hasil skor DAI, MCHI, TNF-α dan IL-6 dianalisis menggunakan uji Kruskal Wallis didapatkan perbedaan yang signifikan (p<0.05). Pada uji Post Hoc Mann Whitney didapatkan perbedaan yang bermakna antara kelompok kontrol positif dengan kontrol negatif, perlakuan I dan perlakuan II yang berbeda signifikan (p<0.05), namun tidak didapatkan perbedaan yang signifikan antara kelompok perlakuan I dan perlakuan II (p>0.05). Hasil kadar hemoglobin dianalisis menggunakan Anova didapatkan perbedaan signifikan (p<0.05). Pada uji Post Hoc Tukey didapatkan perbedaan signifikan antara kontrol positif dengan kontrol negatif, perlakuan I dan perlakuan II (p<0.05)
English Abstract
Ulcerative colitis is part of the Inflammatory Bowel Disease which is characterized by diffuse lesions in the colon. Chronic inflammation that occurs in ulcerative colitis is caused by an imbalance of the immune system in the intestine resulting in an overproduction of pro-inflammatory cytokines such as TNF-α and IL-6. This worsens the inflammatory bowel condition and also plays a role in the extraintestinal manifestation or complications of ulcerative colitis, namely anemia. In addition to an imbalance of the immune system, vitamin D deficiency is also found in about 44% of patients with ulcerative colitis. Vitamin D3 is an active form of vitamin D which not only plays a role in bone remodeling but also in the immune system. Vitamin D3 can play a role in the innate immune system by producing various antimicrobials and increasing recognition of TLR-4, whereas in the adaptive immune system vitamin D3 will inhibit Th1 thereby suppressing pro- inflammatory cytokines and blocking the Nf-κB pathway which also mediates the activation of various cytokines pro-inflammatory. Dextran Sulphate Sodium (DSS) is a substance that can be used to induce colitis in experimental animals. Dextran Sulphate Sodium (DSS) which is toxic to the colon will damage the barrier of the colonic epithelium so that various pathogens can be translocated to the colonic mucosa and activate the immune system especially pro-inflammatory cytokines which further aggravate the damage to the colon. Scoring system that can be used to determine the effects of damage caused by DSS induction in experimental animals are Disease Activity Index (DAI) and Mouse Colitis Histology Index (MCHI). This study aims to prove the effect of administering vitamin D3 can reduce pro- inflammatory cytokines such as TNF-α and IL-6 so colonic damage due to DSS and extraintestinal manifestations can be suppressed. This study used 24 male BALB/c male mice which were divided into 4 groups randomly. The negative control group was only given aquadest, the positive control group (colitis mice model) was given Dextran Sulphate Sodium 3% (DSS 3%) for 7 days, the treatment group I was given 3% DSS for 7 days then given vitamin D3 at a dose of 0.2 μg / 25gram / day for 7 days, the group treatment II was given vitamin D3 at a dose of 0.2 μg / 25gram / day for 7 days and then given DSS 3% for 7 days. During the treatment the Disease Activity Index (DAI) score was calculated then dissected and checked the Mouse Colitis Histology Index (MCHI), TNF-α and IL-6 expression and hemoglobin level. The results were analyzed using Anova and Post Hoc Tukey if the data were normally distributed and homogeneous and Kruskal Wallis and Post Hoc Mann Whitney if the data were not normally distributed and homogeneous. Especially for DAI score data will be analyzed using Friedman and Wilcoxon. The results of the DAI, MCHI, TNF-α and IL-6 scores were analyzed using the Kruskal Wallis test found a significant difference (p <0.05). In the Mann Whitney Post Hoc test, a significant difference was found between the positive and negative control groups, treatment I and treatment II were significantly different (p <0.05), but there were no significant differences between the treatment I and treatment II (p> 0.05) . The results of hemoglobin levels were analyzed using Anova obtained significant differences (p <0.05). In the Post Hoc Tukey test, there was a significant difference between positive and negative controls, treatment I and treatment II (p <0.05) although there was no significant difference between treatment I and treatment II (p> 0.05). From these results it can be concluded that administration of vitamin D3 can suppress the expression of TNF-α and IL-6 through downregulation of pro-inflammatory cytokines and inhibition of the Nf-κB pathway so that it
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| Item Type: | Thesis (Magister) |
|---|---|
| Identification Number: | TES/615.328/MON/p/2020/042001318 |
| Subjects: | 600 Technology (Applied sciences) > 615 Pharmacology and therapeutics > 615.3 Organics drugs > 615.32 Drugs derived from plants and mikroorganisms > 615.323 8 Drugs derived from apiaceae |
| Divisions: | S2/S3 > Magister Ilmu Biomedis, Fakultas Kedokteran |
| Depositing User: | yulia Chasanah |
| Date Deposited: | 13 Sep 2022 03:42 |
| Last Modified: | 13 Sep 2022 03:43 |
| URI: | http://repository.ub.ac.id/id/eprint/194201 |
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