Nauroh, Ninda Farahdina (2019) Pengaruh Nimodipin Terhadap Aktivasi Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) Pada Kultur Neuron Cell Line SH-SY5Y Yang Dipapar Hiperglikemi Kronik. Sarjana thesis, Universitas Brawijaya.
Abstract
Diabetes merupakan disregulasi metabolisme glukosa akibat defek sekresi insulin, penurunan sensitivitas insulin, atau kombinasi keduanya yang menyebabkan kondisi hiperglikemia. Hiperglikemia kronik dapat menyebabkan kerusakan berbagai sistem tubuh terutama saraf dan pembuluh darah yang akan mengarah ke salah satu komplikasi yaitu neuropati diabetik. Neuropati diabetik diinduksi oleh stres oksidatif yang terjadi akibat produksi ROS yang berlebihan. Di sisi lain ROS juga berinteraksi dengan kalsium sehingga peningkatan kalsium dapat menghasilkan enzim penghasil ROS. Saat stres oksidatif meningkat memicu respon transkripsi gen antioksidan yang dimediasi oleh Nrf2. Berdasarkan mekanisme diatas, peneliti mencoba menggunakan nimodipin sebagai calcium channel blocker yang bersifat neuroprotektif untuk menurunkan aktivasi Nrf2. Tujuan penelitian ini untuk melihat pengaruh nimodipin terhadap penurunan aktivasi Nrf2. Penelitian ini dilakukan secara in vitro menggunakan kultur sel neuron SH-SY5Y yang diinduksi hiperglikemi selama 6 hari dengan konsentrasi glukosa 5 mM, 25 mM, dan 50 mM. Kemudian dilakukan panen sel dan diberi nimodipin selama 30 menit dengan dosis 10 nM dan 100 nM. Ekspresi Nrf2 diamati dibawah mikroskop konfokal. Didapatkan hasil nimodipin dengan dosis 10 nM dan 100 nM mampu menurunkan aktivasi Nrf2 pada kultur sel neuron yang sebelumnya telah diinduksi hiperglikemi kronik secara signifikan (p<0,05) pada konsentrasi glukosa 50 mM. Dapat disimpulkan pemberian nimodipin dosis 10 nM dan 100 nM dapat menurunkan aktivasi Nrf2 pada kultur sel neuron yang dipapar hiperglikemi kronik dengan konsentrasi glukosa 50 Mm secara statistik.
English Abstract
Diabetes is a dysregulation of glucose metabolism due to defect in insulin secretion, decreased insulin sensitivity, or a combination of both that causes hyperglycemia. Chronic hyperglycemia can cause damage to various body systems, especially nerves and blood vessels which will lead to one of the complications, namely diabetic neuropathy. Diabetic neuropathy is induced by oxidative stress that results from excessive production of ROS. On the other hand ROS also interacts with calcium so that an increase in calcium can produce ROS-producing enzymes. When oxidative stress increases, it triggers a transcriptional response of antioxidant genes mediated by Nrf2. Based on the above mechanism, the researchers tried to use nimodipin as a calcium channel blocker which is neuroprotective to reduce the activation of Nrf2. The purpose of this study was to look at the effect of nimodipin on decreasing Nrf2 activation. This research was conducted in vitro using SH-SY5Y neuron cell culture induced hyperglycemia for 6 days with glucose concentrations of 5 mM, 25 mM, and 50 mM. Then the cell is harvested and given nimodipin for 30 minutes at a dose of 10 nM and 100 nM. Nrf2 expression was observed under a confocal microscope. The results of nimodipin with doses of 10 nM and 100 nM were able to reduce the activation of Nrf2 in neuron cell culture that had been significantly induced by chronic hyperglycemia (p <0.05) at 50 mM glucose concentration. It can be concluded that administration of nimodipin at 10 nM and 100 nM can reduce Nrf2 activation in neuron cell cultures exposed to chronic hyperglycemia with 50 Mm glucose concentrations statistically.
| Item Type: | Thesis (Sarjana) |
|---|---|
| Identification Number: | SKR/FK/2019/391/052001236 |
| Uncontrolled Keywords: | Hiperglikemi, Sel SH-SY5Y, Nimodipin, Nrf2-Hyperglycemia, SH-SY5Y Cell, Nimodipin, Nrf2 |
| 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: | Fakultas Kedokteran > Pendidikan Dokter |
| Depositing User: | soegeng sugeng |
| Date Deposited: | 18 Aug 2020 03:14 |
| Last Modified: | 22 Oct 2021 07:57 |
| URI: | http://repository.ub.ac.id/id/eprint/180036 |
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