PENGARUH PEMBERIAN EKSTRAK ETANOL DAUN SENDOK (PLANTAGO MAYOR L.) TERHADAP PENGHAMBATAN OVEREKSPRESI GEN REGENERATING-1, PENINGKATAN KADAR CASPASE-3 DAN GAMBARAN HISTOPATOLOGI JARINGAN MUKOSA LAMBUNG TIKUS MODEL HIPERGASTRINEMIA - The Effect of Ethanol Extracts of Plantain (Plantago Mayor L.) on Inhibition of Over-expression of Regenerating-1 Gene, Increasing Caspase-3 Level and Histopatologic Feature of Gastric Mucosa of Hypergastrinemic Rat Model

AbstrakEkstrak etanol daun sendok mengandung banyak zat aktif, termasuk triterpenoid dan flavonoid yang memiliki efek anti proliferatif, anti angiogenesis dan menginduksi apoptosis sel kanker. Hipergastrinemia dapat menginduksi over-ekspresi Gen Regenerating 1, menekan produksi Caspase 3 dan perubahan histopatologi jaringan mukosa lambung. Penelitian ini menganalisis pengaruh pemberian ekstrak etanol daun sendok terhadap penghambatan over ekspresi gen Regenerating 1, peningkatan kadar Caspase 3 dan perubahan histopatologi jaringan mukosa lambung tikus model hipergastrinemia. Penelitian ini dilakukan secara eksperimental dengan post test only with control group design. 28 tikus putih dibagi menjadi empat kelompok. Kelompok I (kontrol) diberi Omeprazol dosis 8mg/200gBB tikus/hari, Ciprofibrate dosis 12,5mg/200gBB tikus/hari dan 3 kelompok studi (Kelompok II, III dan IV diberi Omepr azol dosis 8mg/200gBB tikus/hari, Ciprofibrate dosis 12,5mg/200gBB tikus/hari dan ektrak etanol daun sendok masing-masing dosis 50mg, 100 mg dan 200mg per 200gBB tikus/hari). Semua hewan coba dikorbankan dibawah pengaruh anestesi setelah perlakuan selama 2 bulan. Sampel darah dan gaster hewan coba diambil untuk pemeriksaan kadar gastrin dan Caspase 3 dengan metode ELISA, ekspresi Gen Regenerating1 dengan RT-PCR serta histopatologi jaringan mukosa lambung. Kadar gastrin hewan coba meningkat 3-4 kali kadar gastrin normal (>169 pg/mL). Rerata ekspresi Gen Regenerating 1 terendah terjadi pada Kelompok III (1,226±0,108) Analisis statistik menunjukkan terdapat perbedaan ekspresi Gen Regenerating 1 secara bermakna antara Kelompok III dengan kontrol (nilai p= 0,016;IK 95%). Rerata kadar Caspase 3 tertinggi terdapat pada IV (0,603±0,172ng/mL). Analisis statistik menunjukkan terdapat perbedaan kadar Caspase 3 secara bermakna antara kelompok IV dan Kelompok lainnya (nilai p <0,05;IK 95%). Gambaran histopatologi mukosa lambung menunjukan atropi dan tidak terdapat perbedaan ketebalan jaringan mukosa lambung secara bermakna diantara kelompok penelitian (nilai p=0,092; IK95%). Pemberian ekstrak etanol daun sendok mencegah over-ekspresi Gen Regenerating 1 dengan dosis 100mg/200gBB/hari, meningkatkan kadar Caspase 3 dengan dosis 200mg/200gBB/hari tetapi pada dosis penelitian yang digunakan tidak dapat menghambat perubahan histopatologi jaringan mukosa lambung tikus model hipergastrinemiaKata Kunci: Ekstrak etanol daun sendok, Over ekspresi Gen Regenerating 1, Caspase 3, Histopatologi mukosa lambung, Model HipergastrinemiaAbstractPlantago major L has a lot of active substances, including triterpenoid and flavonoid that show anti proliferative effect, anti angiogenesis and induce cancer cells apoptosis. Hypergastrinemia able to induce overexpression of Regenerating 1 gene, inhibit activation of caspases include Caspase 3 and cause histopathologic alteration of gastric mucosal tissues. This study was to evaluate the effect of Plantago major L extract.on inhibition of Regenerating 1 gene overexpression, increasing of Caspase-3 level and histopathologic alteration of gastric mucosal tissues on hypergastrinemic rat (Rattus norvegicus) model. By experimental study and post test only with control group design, 28 of rats was divided in to 4 groups. Group I as a negative control was given Omeprazole 8mg/200gbw rat and Ciprofibrate dose 12,5 mg/200gbw rat/day and aquadest per oral. Group II was given Omeprazole 8mg/200gbw rat and Ciprofibrate dose 12,5 mg/200gbw rat/day and Plantago major L. extract 50mg/200gbw rat/day per oral. Group III was given Omeprazole 8mg/200gbw rat and Ciprofibrate dose 12,5 mg/200gbw rat/day and Plantago major L. extract 100mg/200gbw rat/day per oral. Group IV was given Omeprazole 8mg/200gbw rat and Ciprofibrate dose 12,5 mg/200gbw rat/day and Plan tago major L. extract 200mg/200gbw rat/day per oral. They were killed after 2 month intervention under anaesthetic. Blood sample and gaster organs were collected for measurement of gastrin and caspase 3 level by using ELISA method, expression of Regenerating 1 gene by RT-PCR and histopatological examination of gastric mucosal tissues. There were increasing of gastrin level of rats up to 3-4 times fold compared to normal level and to indicate hypergastrinemic condition. The lowest average of Regenerating 1 gene expression was found on Group III (1,226±0,108). Statistic analysis show that there were significantly difference of Regenerating 1 gene expression between group III and Control (p= 0,016; 95%CI) The highest average of Caspase-3 level was found on Group IV(0,603±0,172ng/mL) and there were significantly difference of caspase-3 level between group IV and the other Groups (p< 0,05; 95%CI). There were atrophic process on gastric mucosal tissue but there were not significantly difference of gastric mucosal thickness between group (p= 0,092; 95%CI). This study can be concluded that administration of Plantago major L extract able to inhibit overexpression of Regenerating 1 gene by dose 100mg/200gbw rat/day, to increase Caspase 3 level by dose 200mg/200gbw rat/day but can not to inhibit histopathologic alteration of gastric mucosal tissues by using all of the doses. Keyword: Ethanol extract of Plantago major L, Regenerating 1 gene overexpression, Caspase 3, gastric mucosal histopatology, Hypergastrinemia mode