| Abstract: | 肝纖維化是慢性肝損傷的病程演化，通常是由酒精、病毒或其它毒素引起的，其特徵是細胞外基質蛋白如膠原蛋白的過度積累。克弗爾是微生物共生體的混合物，以胞外多糖包覆，主要結構為葡萄半乳聚糖所形成的果凍狀顆粒。研究指出克弗爾具有抗細菌、抗真菌和抗腫瘤活性。本研究利用克弗爾來減輕硫代乙醯胺引起之過氧化傷害所造成的炎症反應，進一步降低肝纖維化之保肝作用。ICR小鼠隨機分為六組。五組腹腔注射300毫克/公斤硫代乙醯胺(thioacetamide, TAA) 每週3次：對照組(Control)每日口服蒸餾水，另試驗組分為克弗爾低劑量組234毫克/公斤(KL)、中劑量組 702毫克/公斤(KM)、高劑量組1170毫克/公斤(KH)與正對照組、67.8毫克/公斤(Postive)共8週；另一組是未處理空白組(Na?ve)。試驗的分子機制中，我們探討肝組織中炎症相關的胸腺基質淋巴細胞生成素(thymic stromal lymphopoietin, TSLP)、介白素-1β (interleukin-1β, IL-1β)、介白素-10 (interleukin-10, IL- 10)、腫瘤壞死因子(tumor necrosis factor-α, TNF-α)、血清麩草醋酸轉胺?(serum aspartate aminotransferase, sAST)和麩丙酮酸轉胺?(serum alanine aminotransferase, sALT)的含量變化，這些可能與肝臟中的過氧化傷害有關，結果顯示，4-羥基壬烯酸(4-hydroxynonenal, 4-HNE)顯著降低，並增加超氧化物歧化?(superoxide dismutase, SOD)的含量，並進一步減輕介白素-6 (interleukin-6, IL-6)、IL-10、單核球趨化蛋白-1 (monocyte chemoattractant protein-1, MCP-1)和TSLP等發炎細胞激素的含量。最後我們利用肝臟羥基脯氨酸與天狼星紅染色來證實克弗爾可降低肝纖維化的產生。總結來說，克弗爾可藉由降低過氧化傷害的炎症反應並進一步降低TAA所造成的肝纖維化。
Liver fibrosis is chronic liver damage usually caused by alcohol, viruses or other toxins and is characterized by an excessive accumulation of extracellular matrix proteins such as collagen. Kefir is a microbial symbiont mixture to form glucogalactan that produces jelly-like grains. It had been reported to possess antibacterial, antimycotic and antitumor activity. In this study, the hepatoprotective effect of kefir on thioacetamide (TAA)-induced liver fibrosis was tested. ICR mice were randomly divided into six groups. Five groups were intraperitoneally injected with 300 mg/kg TAA 3 times/week and daily oral administration of water (Control), 234 mg/kg (KL), 702 mg/kg (KM) and 1170 mg/kg (KH) of kefir and a positive control (Postive) for 8 weeks. Another group is standard chow (Naive) group. The purpose of this study was to establish an animal model of chronic liver damage. At the end of the experiment, we explore thymic stromal lymphopoietin (TSLP), interleukin-1β (IL-1β), IL-10, tumor necrosis factor (TNF-α) in liver tissue by ELISA, and serum aspartate aminotransferase (sAST), serum alanine aminotransferase (sALT) and Sirius red staining. The results indicate that IL-6, IL-10, monocyte chemoattractant protein-1 (MCP-1) and TSLP were significant decrease. Reduced inflammatory responses due to anti-oxidative status by reducing 4-hydroxynonenal (4-HNE) and enhanced superoxide dismutase (SOD) activity and resulting in prevent of liver damage and fibrosis. Effects of kefir on TAA-induced chronic liver damage might be attributed to down-regulation of oxidative related inflammation and further anti-fibrosis. |
