CAJ | 학술논문

目的：观察三黄茵赤汤防治D-氨基半乳糖（D-GalN）联合内毒素（LPS）诱导的大鼠急性肝衰竭氧化应激及肝细胞凋亡的作用。方法48只SD大鼠随机分为正常对照组、模型组、三黄茵赤汤高、中、低剂量组、双环醇组，每组8只。各组对应给药5 d，建立急性肝衰竭模型48 h后处死动物，检测血清中丙氨酸转氨酶、天门冬氨酸氨基转移酶、总胆红素，检测全血中凝血酶原时间、国际标准比率、血浆纤维蛋白原；HE染色观察肝脏病理的变化，检测肝脏组织匀浆液SOD、MDA的含量；免疫组化、免疫印迹检测肝组织caspase-3蛋白表达。结果与模型组比较，三黄茵赤汤高、中、低剂量组、双环醇组均能减少血清中丙氨酸转氨酶、天门冬氨酸氨基转移酶、总胆红素的含量、缩短全血中凝血酶原时间、国际标准比率时间，增加血浆纤维蛋白原的含量（P<0.05）；明显改善肝脏组织病理变化，提高肝脏组织匀浆液SOD活性，减少MDA含量（P<0.05）；下调caspase-3蛋白表达（P<0.05）；三黄茵赤汤中剂量组与双环醇组无统计学差异（P>0.05），高剂量组优于双环醇组（P<0.05）。结论三黄茵赤汤防治D-GalN联合LPS诱导的急性肝衰竭大鼠成量效关系，具有抗氧化的作用；三黄茵赤汤可能通过抗氧化应激抑制caspase3表达从而减少肝细胞凋亡，以达到防治大鼠急性肝衰竭的作用。
목적：관찰삼황인적탕방치D-안기반유당（D-GalN）연합내독소（LPS）유도적대서급성간쇠갈양화응격급간세포조망적작용。방법48지SD대서수궤분위정상대조조、모형조、삼황인적탕고、중、저제량조、쌍배순조，매조8지。각조대응급약5 d，건립급성간쇠갈모형48 h후처사동물，검측혈청중병안산전안매、천문동안산안기전이매、총담홍소，검측전혈중응혈매원시간、국제표준비솔、혈장섬유단백원；HE염색관찰간장병리적변화，검측간장조직균장액SOD、MDA적함량；면역조화、면역인적검측간조직caspase-3단백표체。결과여모형조비교，삼황인적탕고、중、저제량조、쌍배순조균능감소혈청중병안산전안매、천문동안산안기전이매、총담홍소적함량、축단전혈중응혈매원시간、국제표준비솔시간，증가혈장섬유단백원적함량（P<0.05）；명현개선간장조직병리변화，제고간장조직균장액SOD활성，감소MDA함량（P<0.05）；하조caspase-3단백표체（P<0.05）；삼황인적탕중제량조여쌍배순조무통계학차이（P>0.05），고제량조우우쌍배순조（P<0.05）。결론삼황인적탕방치D-GalN연합LPS유도적급성간쇠갈대서성량효관계，구유항양화적작용；삼황인적탕가능통과항양화응격억제caspase3표체종이감소간세포조망，이체도방치대서급성간쇠갈적작용。
Objective To observe the effects of Sanhuangyinchi decoction (SHYCD) pretreatment on acute hepatic failure (AHF) induced by D-galactosamine and lipopolysaccharide (LPS) in rats and explore the possible mechanisms involving antioxidant stress and cell apoptosis-related protein expression. Methods Forty-eight SD rats were randomized equally into control group, AHF model group, high-, medium- and low-dose SHYCD groups, and Bicyclol group. Five days after administration of the corresponding drugs, the rats were challenged with peritoneal D-galactosamine (700 mg/kg) plus LPS (10μg/kg) injections to induce AHF acute hepatic failure except for those in the control group. At 48 h after the injections, blood samples were collected from the rats to detect the levels of ALT, AST, TBIL, PT, INR and FIB, and pathological changes and superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver were examined; immunohistochemistry and western blotting were used to detect caspase-3 protein expression in the liver. Results The levels of ALT, AST, TBIL, TP and INR in the 3 SHYCD groups and Bicyclol group significantly decreased (P<0.05) while FIB significantly increased in comparison with those in the model group. SHYCD obviously ameliorated the pathological changes, enhanced SOD activity (P<0.05), and decreased MDA levels (P<0.05) and caspase-3 expression (P<0.05) in the liver tissue. SHYCD at the medium dose produced similar effects to Bicyclol (P>0.05) and showed better effects at the high dose than Bicyclol (P<0.05). Conclusion SHYCD pretreatment can dose-dependently ameliorate AHF in rats possibly by suppressing antioxidant stress and caspase-3 expression to decrease hepatic cell apoptosis.