复方银杏叶制剂对非酒精性脂肪肝的干预作用及机制

Intervention effect and mechanism of compound Ginkgo biloba preparations on nonalcoholic fatty liver

目的:探究复方银杏叶制剂(CGB)对非酒精性脂肪肝(NAFLD)的干预作用机制。方法:采用高脂饮食诱导C57BL/6小鼠NAFLD模型,于造模第2周起以600,200 mg·kg^(-1)·d^(-1)的CGB灌胃8周,观察小鼠血清生化指标谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、胆固醇(CHOL)、血清内毒素(LPS)水平、肝组织病理变化与肝脏TNF-α表达;电镜观察小肠上皮细胞紧密连接变化,测定ZO-1,Occludin,Claudin-1紧密连接蛋白表达。结果:与正常组比较,模型组小鼠肝脏发生明显脂肪变性,TNF-α表达显著增高(P<0.01);血清ALT,AST,TG,CHOL与LPS水平均显著增高(P<0.01,P<0.05);肠上皮紧密连接结构受损,ZO-1,Occludin,Claudin-1表达显著降低(P<0.01)。与模型组比较,CGB高、低剂量组明显减轻肝组织脂肪变性,TNF-α表达显著降低(P<0.01,P<0.05);血清AST,TG,CHOL与LPS水平均显著降低(P<0.01,P<0.05);肠道紧密连接破坏程度减轻,ZO-1,Occludin表达显著增高(P<0.05)。结论:CGB可以保护肠道紧密连接,减少LPS肠渗漏,缓解肝脏脂肪变性和炎症,防治NAFLD的发生发展。

Objective： To investigate the intervention effect and mechanism of compound Ginkgo biloba （CGB） preparations on nonalcoholic fatty liver disease （NAFLD）. Method： The C57BL/6 mouse NAFLD model was induced with high fat diets. Since the 2nd week after modeling, the mice were orally administered with 600 and 200 mg· kg-1 · d-1CGB for eight weeks. The levels of ala- nine aminotransferase （ALT）, aspartate aminotransferase （AST）, triglyceride （TG）, cholesterol （CHOL） and LPS in serum, as well as pathological changes and expression of tumor necrosis factor-α （TNF-α） in hepatic tissues were observed. Changes in intestinal tight junction proteins ZO-1, Occludin, Claudin-1 in intestinal tissues were determined under microscopy. Result： Compared with the nor- mal group, the model group showed obvious fatty degeneration in rat livers, with notable increase in TNF-α expression （P 〈 0. 01 ）, significant increases in ALT, AST, TG, CHOL and LPS in serum （P 〈 0.01 ,P 〈 0.05 ）, injury in intestinal tight junction proteins, and remarkable declines in ZO-1, Occludin and Claudin-1 （ P 〈 0.01 ）. Compared with the model group, CGB high and low dose groups showed obvious relieves in fatty degeneration in rat livers and injury in intestinal tight junction proteins, significant reductions in TNF-αexpression （P 〈0. 01, P 〈0. 05） and AST, TG, CHOL and LPS in serum （P 〈0. 01 ,P 〈0. 05） and remarkable increases in ZO-1 and Occludin expressions （P 〈 0.05）. Conclusion： CGB can protect intestinal tight junction proteins, reduce intestinal leak- age, relieve fatty degeneration and inflammations in livers and prevent NAFLD occurrence and development.