目的 比较霍山石斛(DHP)、铁皮石斛(DOP)、流苏石斛(DFP)、鼓槌石斛(DCP)、金钗石斛(DNP)和细茎石斛(DMP)等6种石斛多糖对亚急性酒精性肝损伤的保护作用并探讨其可能机制。方法 将实验小鼠随机分为正常对照组、模型对照组、阳性对照组(枸杞多糖200 mg·kg^-1)和6种石斛多糖高(200 mg·kg^-1)、中(100 mg·kg^-1)、低(50 mg·kg^-1)3个剂量处理组。其中,阳性对照组和石斛处理组分别经口灌胃多糖样品30 d,正常对照组和模型对照组给予等体积蒸馏水。从第16天起,模型对照组、阳性对照组和石斛处理组每天经口灌胃30%乙醇(V/V, 10 mL·kg^-1),建立亚急性酒精性肝损伤模型。末次给药后,禁食4 h,麻醉、采血、取肝组织,检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆红素(TBIL)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)的含量,以及肝脏总胆固醇、甘油三酯、乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)、抗氧化酶(SOD、CAT、GSH-PX、GR、GST)、还原型谷胱甘肽(GSH)和丙二醛(MDA)等指标,观察小鼠肝损伤组织病理学变化,并用RT-PCR检测CYP2E1、TNF-α和IL-1的mRNA表达水平。结果 6种石斛多糖对亚急性酒精性肝损伤均有一定程度的保护作用。其中,霍山石斛和铁皮石斛可有效抑制因酒精升高的血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、总胆固醇、甘油三酯、低密度脂蛋白胆固醇及肝组织总胆固醇、甘油三酯和丙二醛的水平,提升因酒精降低的血清低密度脂蛋白胆固醇及肝组织SOD、CAT、GSH-PX、GR、GST和GSH的水平,上调肝组织乙醇脱氢酶和乙醛脱氢酶活性,下调肝组织CYP2E1、TNF-α和IL-1β的表达,减轻酒精对肝脏的病理损伤。结论 石斛多糖可能是通过抑制肝组织氧化损伤和炎性损伤的途径达到抗亚急性酒精性肝损伤的作用。6种石斛多糖抗酒精性肝损伤的活性各有不同,其中以霍山石斛和铁皮石斛最为有效,这可能与不同石斛多糖的相对分子质量、单糖组成和糖苷键链接方式等化学结构不同有关。

OBJECTIVE To investigate and compare the hepatoprotective effects of six different polysaccharides from Dendrobium huoshanense(DHP), D. officinale(DOP), D. fimbriatum(DFP), D. chrysotoxum(DCP), D. nobile(DNP) and D. moniliforme(DMP) against alcohol-induced subacute liver injury in mice. METHODS The mice were randomized into the normal control, alcohol control, positive control and Dendrobium treatment groups. Dendrobium treatment groups were divided into different sub-groups, which were intragastrically administered with high(200 mg·kg^-1), middle(100 mg·kg^-1) and low(50 mg·kg^-1) dosages of six Dendrobium polysaccharides for 30 d, respectively. The positive control group were orally administrated with Lyceum barbarum polysaccharides(200 mg·kg^-1 b.w) for 30 d. The normal control and alcohol control groups were fed with distilled water at the same volume as polysaccharide for 30 d. On the 16th day, the mice in all groups except the normal control group were intragastrically administered with alcohol(30%, V/V, 10 mL·kg^-1) once a day for 14 d to induce subacute liver injury. After the last administration, the mice were fasted for 4 h and euthanized with pentobarbital solution for body weight measurement, blood sampling from abdominal aorta and liver tissue sampling. Then, serum biochemical parameters including alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), total bilirubin(TBIL), total cholesterol(TC), triglycerides(TG), low density lipoprotein cholesterol(LDL-C) and high density lipoprotein cholesterol(HDL-C) were analyzed and hepatic biochemical parameters including TC, TG, alcohol dehydrogenase(ADH), aldehyde dehydrogenase(ALDH), antioxidant enzymes(SOD, CAT, GSH-PX, GR, GST), glutathione(GSH) and malondialdehyde(MDA) were determined. Meanwhile, the histopathological changes in liver tissues were observed and the mRNA expression of hepatic CYP2E1, TNF-α and IL-1β in mice were measured. RESULTS Compared with the alcohol control group, different polysaccharides from six Dendrobium species showed different hepatoprotective effects against alcohol-induced liver injury. Among all tested polysaccharides, DHP and DOP possessed the highest potential for protecting the liver from hepatotoxicity caused by alcohol intake, which was evidenced by the decreased levels of ALT, AST, ALP, TBIL, TC, TG and LDL-C in serum and TC, TG, MDA, CYP2E1, TNF-α and IL-1β in hepatic tissues, the increased levels of HDL-C in serum and SOD, CAT, GSH-PX, GR, GST, GSH, ADH and ALDH in hepatic tissues, and the ameliorated histopathological changes of hepatic tissues. CONCLUSION DHP and DOP can protect against hepatotoxicity caused by alcohol intake in mice by inhibition of hepatic oxidative damage and inflammatory damage. The differences of hepatoprotective effects between different Dendrobium polysaccharides might be related to their differences in chemical structures including molecular weight, monosaccharide compositions and glycosidic linkages.