Hasil Pencarian  ::  Simpan CSV :: Kembali

"Proprotein convertase subtilisin/kexin type 9 adalah protein yang utamanya berasal dari hati dan berperan dalam degradasi reseptor low-density lipoprotein, sehingga menjadikannya target terapeutik yang menjanjikan untuk menunrunkan kolesterol. Pengembangan obat yang menargetkan proprotein convertase subtilisin/kexin type 9 telah menarik banyak perhatian, namun adanya keterbatasan penelitian model in vivo dengan hewan wild type yang mampu merepresentasikan kondisi manusia dapat menghambat proses pengembangan obat. Sebuah studi menunjukkan diet tinggi fruktosa dapat meningkatkan proprotein convertase subtilisin/kexin type 9 pada manusia. Pada penelitian ini dilakukan pengembangan model hewan proprotein convertase subtilisin/kexin type 9 dengan tikus wistar jantan yang diinduksi diet tinggi fruktosa menggunakan variasi durasi induksi selama 3, 4, dan 5 minggu. Parameter yang dinilai adalah kadar Proprotein convertase subtilisin/kexin type 9 di plasma dan hati yang diukur dengan ELISA, serta ekspresinya di hati yang dievaluasi dengan western blot. Pada tikus yang diinduksi fruktosa, terdapat peningkatan signifikan kadar Proprotein convertase subtilisin/kexin type 9 di plasma dan hati dibandingkan dengan kontrol (p<0,05) pada durasi 3 dan 4 minggu untuk plasma, serta durasi 3 minggu untuk hati. Western blot menunjukkan mature proprotein convertase subtilisin/kexin type 9 tereskpresi pada kelompok dengan induksi fruktosa, serta terjadi penurunan ekspresi di minggu ke-3 dan ke-5 jika dibandingkan dengan kontrol. Penelitian ini menunjukkan tikus yang diinduksi fruktosa dapat menjadi pilihan sebagai model hewan proprotein convertase subtilisin/kexin type 9 dengan durasi induksi selama 4 minggu untuk memberikan hasil yang optimal.

---

Proprotein convertase subtilisin/kexin type 9 is a liver-derived protein with an ability to promote degradation of low-density lipoprotein receptor, making it a promising therapeutic target in cholesterol-lowering therapy. The development of drugs targeting proprotein convertase subtilisin/kexin type 9 has attracted considerable attention, but the limited studies of in vivo model with wild type animals that exhibit similarities to that of a human situation could inhibit the drug development process. Recent study has revealed high fructose diet increased proprotein convertase subtilisin/kexin type 9 in humans. In this study, the development of animal model of proprotein convertase subtilisin/kexin type 9 was carried out using rats induced by fructose with duration of induction variation. Plasma and hepatic proprotein convertase subtilisin/kexin type 9 were measured with ELISA, while hepatic proprotein convertase subtilisin/kexin type 9 expression was detected with western blot. A significant increase in plasma and hepatic proprotein convertase subtilisin/kexin type 9 levels were observed in fructose-induced rats following treatment for 3 and 4 weeks, and 4 weeks, respectively, compared to the control group (p<0,05). Western blot showed proprotein convertase subtilisin/kexin type 9 was expressed in fructose-induced groups, and there was a decrease in expression in frucotse- induced group treated for 3 and 5 weeks. This study demonstrate that fructose-induced rat has a potential to be animal model of proprotein convertase subtilisin/kexin type 9, with an induction duration of 4 weeks to provide an optimal result."

"PCSK9 berperan dalam regulasi homeostasis kolestrol dimana meningkatkan kadar LDL-C dengan mendegradasi reseptor LDL (LDL-R). Penelitian mengenai obat inhibitor PCSK9 masih dikembangkan namun metode uji in vivo yang memfasilitasi PCSK9 sangat terbatas terlebih di Indonesia. Maka dilakukan pembuatan model hewan tinggi PCSK9 menggunakan tikus tipe wild yang diinduksi diet tinggi fruktosa mengikuti penelitian yang telah dilakukan pada hamster dan mencit. Penelitian ini dilakukan pada tikus wistar jantan dengan menginduksi diet tinggi fruktosa (HFD) sebanyak 3mL/200grBB selama 3, 4, dan 5 minggu. Plasma dan jaringan ginjal diambil setiap durasi 3, 4 dan 5 minggu dan kadar PCSK9 diukur menggunakan uji ELISA. Sementara ekspresi PCSK9 ginjal dianalisis menggunakan metode western blot. Tikus kelompok HFD menunjukkan kadar PCSK9 plasma yang meningkat signifikan (p<0,05) terhadap kelompok kontrol durasi 3 dan 4 minggu. Durasi optimal peningkatan kadar PCSK9 plasma pada tikus adalah 4 minggu yang menghasilkan kadar PCSK9 sebesar 1389,02 ng/mL. Sementara kadar PCSK9 ginjal menurun signifikan (p<0,05) terhadap kelompok kontrol durasi 3 dan 4 minggu. Ekspresi mature PCSK9 ginjal kelompok HFD lebih tinggi dibandingkan kelompok kontrol.

---

PCSK9 plays a role in the regulation of cholesterol homeostasis which increases LDL-C levels by degrading LDL receptors (LDL-R). Research on PCSK9 inhibitor drugs is still being developed but in vivo test methods that facilitate PCSK9 are limited, especially in Indonesia. Therefore, an animal model for high PCSK9 was created using wild-type rats induced by a high-fructose diet following research that had been conducted on hamsters and mice. This research was conducted on male Wistar rats by inducing a high fructose diet (HFD) of 3mL/200grBW for 3, 4, and 5 weeks. Plasma and kidney tissue were collected every 3, 4 and 5 weeks and PCSK9 levels were measured using the ELISA test. While kidney PCSK9 expression was analyzed using western blot method. The HFD group rats showed significantly increased plasma PCSK9 levels (p<0.05) compared to the control group for 3 and 4 weeks duration. The optimal duration of increasing plasma PCSK9 levels in rats is 4 weeks which results in PCSK9 levels of 1389.02 ng/mL. Meanwhile, kidney PCSK9 levels decreased significantly (p<0.05) compared to the control group for 3 and 4 weeks duration. The expression of kidney mature PCSK9 in the HFD group was higher than the control group."