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"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.

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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."

"Diet tinggi lemak dan gaya hidup dipercaya menjadi faktor risiko yang secara fundamental berpengaruh terhadap kesehatan, terutama sebagai penyebab hiperlipidemia yang mengarah pada gangguan kardiovaskular. Proprotein convertase subtilisin/kexin type 9 (PCSK9) adalah protein yang mengatur degradasi reseptor low-density lipoprotein cholesterol (LDL) sebagai penentu kadar LDL plasma, meningkatkan aktivasi platelet dan inflamasi vaskular. Penelitian eksperimental melalui pemberian variasi diet tinggi lemak HFD I, HFD II, dan HFD III dievaluasi pengaruhnya terhadap profil lipid dan kadar PCSK9 plasma perlu dilakukan dalam upaya pengembangan model hewan hiperlipidemia. Profil lipid diukur menggunkan spektrofotometer UV-Vis dan kadar PCSK9 melalui ELISA dari 20 sampel plasma darah tikus Wistar jantan. Hasil evaluasi menunjukkan bahwa variasi diet tinggi lemak selama 10 minggu meningkatkan kadar kolesterol total dan trigliserida secara signifikan (p<0,001) dibandingkan dengan kelompok normal, perbandingan antarkelompok induksi berbeda signifikan (p<0,001), dan berhasil mencapai kondisi hiperlipidemia. Terdapat korelasi positif yang kuat dan signifikan antara kadar kolesterol total (r= 0,883; p= <0,001) dan trigliserida (r= 0,817; p= <0,001) terhadap kadar PCSK9 plasma. Kadar PCSK9 plasma pada kelompok induksi diet tinggi lemak berbeda signifikan (p=0,029) dibandingkan dengan kelompok normal. Pada penelitian ini, semua variasi diet tinggi lemak mampu meningkatkan kadar kolesterol total, trigliserida, dan kadar PCSK9 plasma dengan peningkatan terbesar terdapat pada komposisi HFD III yang mengandung 15% mentega dan 50% lemak kambing dengan komposisi asam lemak jenuh dan lemak trans yang relatif lebih tinggi, Penelitian lebih lanjut diperlukan untuk menganalisis pengaruhnya terhadap kerusakan jaringan vaskular pada model hewan hiperlipidemia.

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High-fat diet and lifestyle are acknowledged to be risk factors that fundamentally affect health, especially as a cause of hyperlipidemia that leads to cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein that regulates the degradation of low-density lipoprotein cholesterol (LDL) receptors as a determinant of plasma LDL levels, increases platelet activation and vascular inflammation. Experimental research through the provision of high-fat diet variations HFD I, HFD II, and HFD III evaluated its effect on lipid profiles and plasma PCSK9 levels requirements to be carried out to develop animal models of hyperlipidemia. Lipid profiles were measured using a spectrophotometer UV-Vis and PCSK9 levels by ELISA from 20 blood plasma samples of male Wistar rats. The results of the evaluation showed that the variation of a high-fat diet for 10 weeks increased total cholesterol and triglyceride levels significantly (p<0,001) compared to the normal group, the comparison between the induction groups was significantly different (p<0,001), and managed to achieve hyperlipidemia. There was a strong and significant positive correlation between total cholesterol levels (r= 0,883; p= <0,001) and triglycerides (r= 0,817; p= <0,001) on plasma PCSK9 levels. Plasma PCSK9 levels in the high-fat diet induction group were significantly different (p=0,029) compared to the normal group. In this study, all variations of a high-fat diet were able to increase total cholesterol, triglycerides, and plasma PCSK9 levels with the considerable increase in the composition of HFD III which contained 15% butter and 50% goat fat with relatively higher saturated and trans fatty acid compositions. Further research is required to analyze its effect on vascular tissue damage in animal models of hyperlipidemia."