CAJ | 학술논문

目的探讨甘氨酸对非酒精性脂肪性肝炎（NASH）大鼠肝组织中Toll样受体4（TLR4）及髓系触发受体-1、2（TREM-1、2）表达的影响。方法54只雄性SD大鼠，随机分成三组：对照组、模型组和甘氨酸组。第4、8、12周末分批处死，检测血浆转氨酶（ ALT、AST）、三型前胶原（ PCⅢ）、肿瘤坏死因子-α（ TNF-α）及内毒素（ ET）水平。取肝组织分别做：HE染色；免疫组化检测TLR4蛋白表达；RT-PCR检测TREM-1、2 mR-NA表达。结果（1）同期模型组血浆ALT、AST、PCⅢ、TNF-α、ET水平均较对照组增高（ P＜0.05），甘氨酸组与同期模型组相比则降低（ P＜0.05）。（2）与同期对照组相比，模型组TREM-1 mRNA与TLR4蛋白表达水平增高、TREM-2 mRNA表达水平降低（ P＜0.05）；同期甘氨酸组与模型组相比结果恰好相反。（3） TLR4表达与TREM-1表达呈正相关关系，与TREM-2表达呈负相关关系。结论（1）建立大鼠NASH模型过程中伴有肠源性内毒素血症形成。（2）TLR4在NASH形成中表达水平逐渐增高，并引发一系列炎症介质反应，加重肝脏损害程度。（3）在NASH形成中TREM-1与TREM-2基因水平比例失调，可能起到加速NASH发生发展的作用。（4）甘氨酸通过拮抗内毒素，下调TLR4、TREM-1水平，上调TREM-2水平，减轻NASH程度，对防治NASH有重要指导意义。
목적탐토감안산대비주정성지방성간염（NASH）대서간조직중Toll양수체4（TLR4）급수계촉발수체-1、2（TREM-1、2）표체적영향。방법54지웅성SD대서，수궤분성삼조：대조조、모형조화감안산조。제4、8、12주말분비처사，검측혈장전안매（ ALT、AST）、삼형전효원（ PCⅢ）、종류배사인자-α（ TNF-α）급내독소（ ET）수평。취간조직분별주：HE염색；면역조화검측TLR4단백표체；RT-PCR검측TREM-1、2 mR-NA표체。결과（1）동기모형조혈장ALT、AST、PCⅢ、TNF-α、ET수평균교대조조증고（ P＜0.05），감안산조여동기모형조상비칙강저（ P＜0.05）。（2）여동기대조조상비，모형조TREM-1 mRNA여TLR4단백표체수평증고、TREM-2 mRNA표체수평강저（ P＜0.05）；동기감안산조여모형조상비결과흡호상반。（3） TLR4표체여TREM-1표체정정상관관계，여TREM-2표체정부상관관계。결론（1）건립대서NASH모형과정중반유장원성내독소혈증형성。（2）TLR4재NASH형성중표체수평축점증고，병인발일계렬염증개질반응，가중간장손해정도。（3）재NASH형성중TREM-1여TREM-2기인수평비례실조，가능기도가속NASH발생발전적작용。（4）감안산통과길항내독소，하조TLR4、TREM-1수평，상조TREM-2수평，감경NASH정도，대방치NASH유중요지도의의。
Objective To explore the effect of glycine on expression of toll-like receptor 4 ( TLR4 ) and triggering receptor expressed on myeloid cells-1, 2 ( TREM-1, 2 ) in rats liver with non-alcoholic steatohepatitis (NASH).Methods 54 male sprague dawley(SD)rats were randomly divided into 3 groups:control group,model group and glycine group.They were killed at the 4th,8th and 12th weekend respectively,and blood samples were collected to detect the levels of ALT , AST, TNF-α, PcⅢ and ET.The pathological change of liver tissue were observed by hematein eosin ( HE) stain.The expression of TREM-1,2 in liver tissue were detected by RT-PCR on mRNA level,and TLR4 was detected immunohistochemistry on protein level .Results (1) In the same periods the levels of ALT,AST,PcⅢ,TNF-αand ET in model group were higher than those in control group (P<0.05),but those in glycine group were lower than those in model group ( P<0.05 ) .( 2 ) In the same period the expression of TREM-1 on mRNA level and TLR4 on protein level in model group were increased compared with those in control group(P<0.05),but those in glycine group were decreased compared with those in model group (P <0.05), whereas the results of TREM-2 were just the reverse .( 3 ) Bivariate correlation showed that there was positive correlation between the expression of TLR 4 and TREM-1,but negative correlation between the expression of TLR 4 and TREM-2.Conclusions (1)The model of rat with NASH was established together with the formation of intestinal endotoxemia(IETM).(2)In the process of establishment the expression of TLR 4 is increased followed by a series of inflammation response,which aggravate liver damage.(3)The proportion of TREM-1 to TREM-2 was imbalanced in model group ,which would accelerated the process of NASH .( 4 ) Glycine may alleviate NASH though downregulate the expression of TLR4 and TREM-1 and upregulate the expression of TREM-2 by antagonizing endotoxin ,which will play an important role in the prevention and treatment of NASH .