CAJ | 학술논문

目的：探讨一氧化碳释放分子-2对小鼠急性肝功能衰竭（ALF）的保护作用及机制。方法雄性 C57BL／6小鼠30只随机分为对照组、模型组和保护组，每组10只。通过一次性腹腔注射脂多糖／D-氨基半乳糖（LPS／D-GalN）构建小鼠 ALF 的动物模型，CORM-2于造模前30 min 行尾静脉注射，造模后6 h 分别留取血清、肝组织标本。生化分析仪检测血清中 ALT、AST 水平，HE 观察肝脏病理改变，酶联免疫吸附法（ELISA）检测血清中 TNF-α和 IL-6的水平，反转录酶-聚合酶链反应（RT-PCR）检测肝组织中 TNF-α和 IL-6 mRNA 的表达。结果保护组小鼠血清 ALT [（1274．60±157．24） U／L 比（3499．00±136．19）U／L]和 AST[（1151．50±244．58）U／L 比（4079．50±481．11）U／L]水平均明显低于模型组（均 t 1＝33．81，t2＝17．16，P ＜0．05）；与模型组比较，保护组肝组织炎性细胞浸润明显减少，肝细胞坏死程度明显减轻[（0．14±0．05）比（0．37±0．05），t＝10．29，P ＜0．05]；保护组小鼠血清和肝组织中 TNF-α[（139．60±28．39）pg／mL 比（447．34±128．17）pg／mL、（0．31±0．03）比（0．69±0．05）]和 IL-6[（215．21±85．16）pg／mL 比（1461．58±244．90）pg／mL、（0．33±0．03）比（0．72±0．05）]表达水平明显低于模型组（均 t 1＝7．41，t2＝20．61，t3＝15．20，t4＝21．15，P ＜0．05）。结论CORM-2能够抑制小鼠 ALF 时的炎性反应，减轻肝脏病理损伤，其机制可能与抑制促炎细胞因子 TNF-α和 IL-6的释放有关。
목적：탐토일양화탄석방분자-2대소서급성간공능쇠갈（ALF）적보호작용급궤제。방법웅성 C57BL／6소서30지수궤분위대조조、모형조화보호조，매조10지。통과일차성복강주사지다당／D-안기반유당（LPS／D-GalN）구건소서 ALF 적동물모형，CORM-2우조모전30 min 행미정맥주사，조모후6 h 분별류취혈청、간조직표본。생화분석의검측혈청중 ALT、AST 수평，HE 관찰간장병리개변，매련면역흡부법（ELISA）검측혈청중 TNF-α화 IL-6적수평，반전록매-취합매련반응（RT-PCR）검측간조직중 TNF-α화 IL-6 mRNA 적표체。결과보호조소서혈청 ALT [（1274．60±157．24） U／L 비（3499．00±136．19）U／L]화 AST[（1151．50±244．58）U／L 비（4079．50±481．11）U／L]수평균명현저우모형조（균 t 1＝33．81，t2＝17．16，P ＜0．05）；여모형조비교，보호조간조직염성세포침윤명현감소，간세포배사정도명현감경[（0．14±0．05）비（0．37±0．05），t＝10．29，P ＜0．05]；보호조소서혈청화간조직중 TNF-α[（139．60±28．39）pg／mL 비（447．34±128．17）pg／mL、（0．31±0．03）비（0．69±0．05）]화 IL-6[（215．21±85．16）pg／mL 비（1461．58±244．90）pg／mL、（0．33±0．03）비（0．72±0．05）]표체수평명현저우모형조（균 t 1＝7．41，t2＝20．61，t3＝15．20，t4＝21．15，P ＜0．05）。결론CORM-2능구억제소서 ALF 시적염성반응，감경간장병리손상，기궤제가능여억제촉염세포인자 TNF-α화 IL-6적석방유관。
Objective To investigate the protective effect and mechanisms of carbon monoxide releasing molecule (CORM-2)on acute liver failure (ALF)in mice.Methods Male C57BL/6 mice were randomly divided into three groups:control, model and protected group. The ALF animal models were induced by intraperitoneal injection of lipopolysaccharide/D-galactosamine (LPS/D-GalN).CORM-2 was administered via tail vein 30 minutes before LPS/D-GalN treatment.All serum samples and liver specimens were collected for detection in 6 hours after the administration of LPS/D-GalN.The serum levels of alanine aminotransferase (ALT)and aspartate aminotransferase (AST)were measured by automatic biochemical analyzer.The liver pathologic changes were observed by light microscopy using hematoxylin and eosin (HE)staining.The serum levels of tumor necrosis factor-α (TNF-α)and interleukin-6 (IL-6)were measured by enzyme linked immunosorbent assay (ELISA).The expression of TNF-α and IL-6 mRNA in the liver tissues were measured by reverse transcript polymerase chain reaction (RT-PCR)in each group.Results The serum levels of ALT [(1274.60 ± 157.24)U/L vs (3499.00±136.19)U/L]and AST [(1151 .50±244.58)U/L vs (4079.50± 481 .11)U/L]in protected group were significantly lower than those in model group (t 1 =33.81 ,t2 =17.16 both P <0.05 ).Massive inflammatory cells infiltration and hepatocyte necrosis were widely spread in model group,while liver injuries were obviously relieved in protected group [(0.14±0.05)vs (0.37±0.05),t =10.29,P <0.05 ].The serum levels of TNF-α [(139.60 ±28.39) pg/mL vs (447.34 ±128.17)pg/mL]and IL-6 [(215.21 ±85.16)pg/mL vs (1461 .58 ±244.90)pg/mL]in protected group were significantly reduced compared with model group (t 1 =7.41 ,t2 =20.61 both P <0.05).TNF-αmRNA [(0.31±0.03)vs (0.69±0.05 )]and IL-6 mRNA [(0.33 ±0.03 )vs (0.72 ±0.05 )]measured by RT-PCR in live tissues of protected group were also significantly lower than that in model group (both P < 0.05 ).Conclusion CORM-2 could remarkably inhibit the inflammatory activity and attenuate liver injury,mechanism of which might be related to inhibiting the release of proinflammatory cytokines TNF-αand IL-6.