Peran Acth4-10pro8-Gly9-Pro10 dan Inhibitor Hmg-Coa Reduktase Dalam Peningkatan Bcl-2 dan Bdnf terhadap Hasil Akhir Klinis Penderita Kontusio Serebri

Abstract

Background: Traumatic brain injury (TBI) is a major public health concern in developing and developed countries. Treatment and improvement of clinical outcome are still a challenge in medical science. Apoptosis in secondary brain injury process involves in elaboration of brain damage. Bcl-2 (B Cell Lymphoma-2) and BDNF (Brain-Derived Neurotrophic Factor) proteins have an important role in modulating apoptosis process. Bcl-2 and BDNF level escalation will give anti-apoptotic effect and brain plasticity escalation. Purpose: To compare the effect between standard therapy, standard therapy with ACTH4-10Pro8Gly9Pro10, and standard therapy with HMG CoA reductase inhibitor of serum Bcl-2 and BDNF level, clinical outcome and length of stay. Methods: This research is a true experimental study pre-post test control group design with single blind that conducted at Department of Neurosurgery and Department of Clinical Pathology University of Sumatera Utara/ H. Adam Malik Hospital with 60 patients with moderate head injury and severe head injury which did not have any indication for surgery. Serum Bcl-2 and BDNF measurements have been done with ELISA method. Results: The subjects were divided into two groups of moderate head injury and severe head injury. Both of the groups divided again into 3 groups according to the treatment which contain 20 subjects in each groups. Serum was taken from each respondent on day one and day five for Bcl-2 and BDNF level measurement. Moderate head injury subjects, Bcl-2 level on day one (standard: 1.68 ± 1,34ng/mL; ACTH4-10Pro8Gly9Pro10±: 1,93 1.35ng/mL; inhibitor HMG CoA reductase: 1.83 ± 1,15ng/mL) and day five (standard: 1.66± 1.06ng/mL; ACTH4-10Pro8Gly9Pro10±:3.81 1.0ng/mL, inhibitor HMG CoA reductase: 2.13± 0.56ng/mL). BDNF level on day one (standard: 866,79 ± 478,52 pg/mL; ACTH4-10Pro8Gly9Pro10: 955,81 ± 445,68 pg/mL; inhibitor HMG CoA reductase: 1015,71 ± 493,34 pg/mL) and day five (standard: 1026,19 ± 546,66 pg/mL; ACTH4-10Pro8Gly9Pro10 Severe head injury subjects, Bcl-2 level on day one (standard: 1,49 ± 1,00 ng/mL; ACTH: 1764,69 ± 559,69 pg/mL, inhibitor HMG CoA reductase: 1179,02 ± 417,22 pg/mL). 4-10Pro8Gly9Pro10±: 1,721.40ng/mL; inhibitor HMG CoA reductase: 1,55 ± 0,98 ng/mL) and day five (standard: 1,64 ± 0,61 ng/mL; ACTH4-10Pro8Gly9Pro10:4,02 ± 1,119 ng/mL, inhibitor HMG CoA reductase: 2,00 ± 0,91 ng/mL). BDNF level on day one (standard: 941,39 ± 486,84 pg/mL; ACTH4-10Pro8Gly9Pro10: 990,30 ± 454,03pg/mL; inhibitor HMG CoA reductase: 953,83 ± 459,50 pg/mL) and day five (standard: 1028,45 ± 564,51 pg/mL; ACTH4-10Pro8Gly9Pro10 This research found weak correlation between Bcl-2 and BDNF with Barthel index and Mini Mental Score Examination (MMSE), but there is significant difference length of stay between three groups of treatment. The shortest length of stay on moderate head injury and severe head injury is group with ACTH : 1769,80 ± 597,48 pg/mL, inhibitor HMG CoA reductase: 1221.73 ± 390,66 pg/mL). 4-10Pro8Gly9Pro10 therapy (p<0,05; CI 95%). Conclusion: ACTH4-10Pro8Gly9Pro10 therapy significantly increased Bcl-2 and BDNF serum level compared with standard group and HMG CoA reductase inhibitor group on moderate head injury and severe head injury. ACTH4-10Pro8Gly9Pro10 therapy also significantly decrease length of stay.

Latar belakang: Cedera kepala merupakan masalah kesehatan utama di negara maju dan berkembang. Pengobatan dan peningkatan hasil akhir pada penderita cedera kepala masih menjadi tantangan dalam bidang kedokteran.Apoptosis pada proses cedera kepala sekunder berperan dalam perluasan kerusakan jaringan otak. Protein Bcl-2 dan BDNF mempunyai peran penting dalam memodulasi proses apoptosis. Peningkatan kadar Bcl-2 an BDNF akan memberikan efek anti-apoptosisdan meningkatkan plastisitas otak.Efek ACTH4-10Pro8-Gly9-Pro10dan HMG CoA reduktase pada cedera kepala masih belum diketahui. Tujuan: Untuk menganalisis peran ACTH4-10Pro8-Gly9-Pro10 dan inhibitor HMG CoA reduktase dalam peningkatan Bcl-2dan BDNF terhadap hasil akhir klinis penderita kontusio serebri. Metode: Penelitian ini merupakan penelitian true experimental study pre-post test control group design dengan single blind yang di lakukan di Departemen Bedah Saraf dan Departemen Patologi Klinik FK-USU/RS HAM.Penelitianini dilakukan pada 60 penderita cedera kepala sedang (CKS) dan 60 penderita cedera kepala berat (CKB) yang tidak diindikasikan tindakan operasi.Pemeriksaan Bcl-2 dan BDNF serum dilakukan dengan metode ELISA. Hasil: Subjek terpilih terdiri dari kelompok CKS dan CKB. Kedua kelompok ini dibagi lagi berdasarkan perlakuan dalam tiga kelompok yang masing-masing terdiri dari 20 orang. Serum diambil dari semua subjek pada hari pertama dan kelima untuk dilakukan pemeriksaan kadar Bcl-2 dan BDNF. Pada penderita CKS, kadar Bcl-2 hari pertama (standar: 1.68 ± 1,34ng/mL; ACTH4-10Pro8Gly9Pro10±: 1,93 1.35ng/mL; inhibitor HMG CoA reduktase: 1.83 ± 1,15ng/mL) dan hari kelima (standar: 1.66± 1.06ng/mL; ACTH4-10Pro8Gly9Pro10±:3.81 1.0ng/mL, inhibitor HMG CoA reduktase: 2.13± 0.56ng/mL). Kadar BDNF hari pertama (standar: 866,79 ± 478,52 pg/mL; ACTH4-10Pro8Gly9Pro10: 955,81 ± 445,68 pg/mL; inhibitor HMG CoA reduktase: 1015,71 ± 493,34 pg/mL) dan hari kelima (standar: 1026,19 ± 546,66 pg/mL; ACTH4-10Pro8Gly9Pro10 Pada penderita CKB, kadar Bcl-2 hari pertama (standar: 1,49 ± 1,00 ng/mL; ACTH: 1764,69 ± 559,69 pg/mL, inhibitor HMG CoA reduktase: 1179,02 ± 417,22 pg/mL). 4-10Pro8Gly9Pro10±: 1,721.40ng/mL; inhibitor HMG CoA reduktase: 1,55 ± 0,98 ng/mL) dan hari kelima (standar: 1,64 ± 0,61 ng/mL; ACTH4-10Pro8Gly9Pro10:4,02 ± 1,119 ng/mL, inhibitor HMG CoA reduktase: 2,00 ± 0,91 ng/mL). Kadar BDNF hari pertama (standar: 941,39 ± 486,84 pg/mL; ACTH4-10Pro8Gly9Pro10: 990,30 ± 454,03pg/mL; inhibitor HMG CoA reduktase: 953,83 ± 459,50 pg/mL) dan hari kelima (standar: 1028,45 ± 564,51 pg/mL; ACTH4-10Pro8Gly9Pro10: 1769,80 ± 597,48 pg/mL, inhibitor HMG CoA reduktase: 1221.73 ± 390,66 pg/mL). Berdasarkan perhitungan statistik terdapat peningkatan kadar Bcl-2 dan BDNF yang signifikan pada kelompok perlakuan ACTH4-10Pro8-Gly9-Pro10 Pada penelitian ini didapati korelasi yang lemah antara kadar Bcl-2 dan BDNF dengan Barthel indeks dan Mini Mental Score Examination (MMSE), tetapi dijumpai perbedaan lama rawatan antara ketiga kelompok perlakuan. Lama rawatan paling singkat adalah pada kelompok ACTHdibandingkan dengan perlakuan standar dan inhibitor HMG CoA reduktase. 4-10Pro8Gly9Pro10,baik pada CKS maupun CKB (p<0,05; CI 95%). Kesimpulan: Pemberian ACTH4-10Pro8Gly9Pro10secara signifikan meningkatkan kadar serum Bcl-2 dan BDNF dibandingkan dengan kelompok standar dan kelompok inhibitor HMG CoA reduktase baik pada CKS dan CKB. Pemberian ACTH4-10Pro8Gly9Pro10secara signifikan juga menurunkan lama rawatan di rumah sakit.