CAJ | 학술논문

目的：观察小檗碱对胆碱-蛋氨酸缺乏（MCD）饮食诱导非酒精性脂肪性肝炎（NASH）模型小鼠肝组织巨噬细胞M1、M2表型转化的作用。方法雄性C57 BL／6小鼠40只随机分为4组（每组10只）：正常组（饲喂常规饲料），模型组（饲喂MCD饲料），罗格列酮干预组（30mg／kg）和小檗碱干预组（150mg／kg），采用预防给药方式，连续2周。通过组织病理学评分评估动物模型及药物疗效；采用ELISA法检测血清肿瘤坏死因子-α（ TNF-α）、白细胞介素（ IL-6）及IL-10水平；流式细胞术检测肝组织中M1、M2型巨噬细胞的数量和比值。结果罗格列酮和小檗碱可显著改善MCD饮食诱导小鼠NASH的病理程度，显著下调血清中TNF-α水平（P＜0．05），显著上调血清中IL-10水平（P＜0．05），显著降低肝组织中M1型巨噬细胞及增加M2型巨噬细胞的数量，降低M1／M2比值（ P＜0．01）。结论小檗碱对MCD饮食诱导小鼠NASH有较好改善作用，其部分药理机制为：调节肝组织中巨噬细胞表型转化，增加M2型巨噬细胞比例，上调抗炎细胞因子的分泌。
목적：관찰소벽감대담감-단안산결핍（MCD）음식유도비주정성지방성간염（NASH）모형소서간조직거서세포M1、M2표형전화적작용。방법웅성C57 BL／6소서40지수궤분위4조（매조10지）：정상조（사위상규사료），모형조（사위MCD사료），라격렬동간예조（30mg／kg）화소벽감간예조（150mg／kg），채용예방급약방식，련속2주。통과조직병이학평분평고동물모형급약물료효；채용ELISA법검측혈청종류배사인자-α（ TNF-α）、백세포개소（ IL-6）급IL-10수평；류식세포술검측간조직중M1、M2형거서세포적수량화비치。결과라격렬동화소벽감가현저개선MCD음식유도소서NASH적병리정도，현저하조혈청중TNF-α수평（P＜0．05），현저상조혈청중IL-10수평（P＜0．05），현저강저간조직중M1형거서세포급증가M2형거서세포적수량，강저M1／M2비치（ P＜0．01）。결론소벽감대MCD음식유도소서NASH유교호개선작용，기부분약리궤제위：조절간조직중거서세포표형전화，증가M2형거서세포비례，상조항염세포인자적분비。
Objective To determine the efficacy of berberine in the treatment of non-alcoholic steatohepatitis ( NASH) , and to investigate the regulating effect on macrophage phenotype transformation in hepatic tissue on methionine -choline deficiency (MCD) diet induced NASH mice.Methods Fourty male C57BL/6 mice were randomly divided into 4 groups (10 mice per group): the normal group (fed with normal diet), the NASH model group (fed with MCD diet), rosiglitazone treatment group (30mg/kg) and berberine treatment group (150mg/kg).Drugs were adopted in the preventive intervention method for 2 weeks.The hepatic histopathological method was adopted to evaluate the drug therapeutic effect.The serum levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, and IL-10 were examined with ELISA method.M1 and M2 phenotype were detected by flow cytometry .Results The results showed berberine improved the degree of hepatic histopathology .Berberine not only reduced the level of TNF-α, but also increased the level of IL-10 in serum on NASH mice significantly ( P <0.05 ) . Flow cytometry data indicated that berberine decreased M 1 type macrophages and increased M 2 type macrophages in liver tissue .The ratio of M1/M2 was significantly decreased in berberine and rosiglitazone treated group ( P <0.01 ) .Conclusion Berberine may improve the hepatic pathological process in MCD diet induced NASH model possibly through modulating macrophage phenotype transformation , i.e.The ratio of M2 type is more than M1 type in hepatic tissue , and increasing anti-inflammatory cytokines .