Pengaruh Simvastatin Terhadap Kadar Proliferasi Limfosit Mencit Balb/C yang Diinduce Sepsis dengan LPS
ABSTRACT

Background: Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase is an effective agent in lowering lipids. Statins also modify intercellular interactions and cellular chemotaxis and potentially affect the immune system by inhibiting T lymphocyte interactions between cellular adhesion molecule LFA-1, ICAM-1 and IFN-ɤ which play a role in the expression of MHC II on APC and an important process in T cell activation. Inhibition of MHC II expression resulted in inhibition of CD4 lymphocyte activation, resulting in decreased differentiation of Th1 and proinflamatory cytokines.

Objective: To determine dose-effect relationship of lymphocyte proliferation level in balb/c mice induced by intraperitoneal lipopolysaccharide after administration of simvastatin.

Methods: A randomized post test only controlled group laboratoric experimental studied in 20 Balb/c mice divided into 4 group and injected intraperitoneally with lipopolysaccharide 10mg/BW and 0,03 mg doses of simvastatin; 0,06 mg and 0,12 mg orally. The controle group KI, K2 which received 0,03 mg simvaststin, K3 received 0,006 mg simvaststin, and K4 which received 0,12 mg of simvastatin. Examination of cultured spleen lymphocyte taken after 72 hours of administration of simvastatin. Parametric ANOVA is used as a statistical test followed by a posteriori test.

Result: Mean levels of lymphocytes in the KI group (1.546 + 0.106), K2 (0.541 + 0.046), K3 (0.471 + 0.013) and K4 (0.02 + 0.553). There were significant decreased in lymphocyte levels in the K2, K3 and K4 groups compared to K1 (p< 0.05). There were no significant differences between K2, K3 and K4 groups (p>0.05) but found significant differences between groups K3 to K4 (p<0.05).

Conclusion: Simvastatin significantly decreased the levels of lymphocyte proliferation in mice that received intraperitoneal injection of LPS compared with mice that did not receive simvastatin. 0.06 mg dose of simvastatin had the greatest effect to suppress levels of lymphocyte proliferation.

Keywords : lipopolysaccharide, simvastatin, lymphocyte proliferation
ABSTRAK

Latar Belakang: Statin, inhibitor 3-hidroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase merupakan agen yang paling efektif dalam menurunkan lipid dan mempunyai efek pleiotrofik yaitu anti inflamatori dan immunomodulatori. Statin juga memodifikasi interaksi interseluler dan kemotaksis seluler pada sistem imun serta berpotensi mempengaruhi limfosit T dengan cara menghambat iinteraksi antara adhesi molekul seluler leukocyte function-associated antigen-1 (LFA-1) dan intercellular adhesion molecule-1 (ICAM-1), juga menurunkan interferon gamma (IFN -ɣ) yang berperan dalam ekspresi class II major histocompatibilty complex (MHC II) pada antigen precenting cells (APC) dan merupakan proses penting dalam aktivasi sel T. Penurunan ekspresi MHC II berakibat pada inhibisi aktivasi CD 4 limfosit, sehingga mengakibatkan penurunan diferensiasi T helper-1 (Th1) dan pelepasan sitokin proinflamasi juga menurun.

Tujuan: Membuktikan efek simvastatin dosis bertingkat peroral pada mencit yang diberi LPS intraperitoneal terhadap penurunan kadar proliferasi limfosit.

Metode: Penelitian eksperimental laboratorik dengan desain randomized post test only controlled group pada 20 ekor mencit Balb/c yang disuntik lipopolisakarida 10 mg/KgBB intraperitoneal dan simvastatin dosis 0,03 mg, 0,06 mg dan 0,12 mg peroral. Mencit dibagi menjadi 4 kelompok secara random, yaitu K1 sebagai control,  K2 yang mendapat simvastatin 0,03 mg, K3 yang mendapat simvastatin 0,06 mg dan K4 yang mendapat simvastatin 0,12 mg. Pemeriksaan limfosit diambil dari kultur limpa setelah 72 jam pemberian simvastatin. Uji statistik yang digunakan adalah parametrik ANOVA dan dilanjutkan Posteriori

Hasil: Kadar rerata limfosit kelompok K1 (1,546 ± 0,106), K2 (0,541 ± 0,046), K3 (0,471 ± 0,013) dan K4 (0,553 ± 0,02). Terdapat penurunan kadar limfosit secara signifikan pada kelompok K2, K3 dan K4 dibanding K1 dengan p <0,05. Tidak terdapat perbedaan bermakna antara kadar limfosit kelompok K2 dengan kelompok K3 dan K4 ( p>0,05) tetapi didapatkan perbedaan bermakna antara kelompok K3 dibandingkan kelompok K4 ( p<0,05).

Simpulan: Simvastatin secara signifikan menurunkan kadar proliferasi limfosit pada mencit yang diberi LPS intraperitoneal. Dosis 0,06 mg memiliki efek menekan kadar proliferasi limfosit paling besar.

Kata kunci : simvastatin, lipopolisakarida, proliferasi limfosit
Artikel Sekarang
Dipublikasi pada 01 November 2013
Penulis :
» Made Ryan Kharmayani
» Haris Lutfi
» Danu Soesilowati
Kategori : Penelitian
Berkas Artikel (PDF)
Dari Jurnal
Volume V Nomor 3, November 2013 Cover JAI
Daftar Isi | Berkas Full (PDF)

 

Beri komentar

A PHP Error was encountered

Severity: Warning

Message: Unknown: write failed: Disk quota exceeded (122)

Filename: Unknown

Line Number: 0

A PHP Error was encountered

Severity: Warning

Message: Unknown: Failed to write session data (files). Please verify that the current setting of session.save_path is correct (/var/cpanel/php/sessions/ea-php56)

Filename: Unknown

Line Number: 0