复方中药对大鼠高脂饮食所致脂肪性肝炎肝组织氧化和抗氧化系统的影响

Effects of compound from Chinese medicine on oxidation and anti-oxidation system of rat liver with steatohepatitis induced by high-fat diets

目的:探讨氧应激和脂质过氧化在高脂饮食所致脂肪性肝炎形成中的作用,复方中药防治非乙醇性脂肪性肝炎的作用机制.方法:雄性SD大鼠60只随机分组为6组,每组10只.正常组普通饲料喂养;模型Ⅰ组、Ⅱ组喂高脂饲料;中药治疗Ⅰ、Ⅱ组分别在喂饲高脂饲料9wk、13wk予复方中药灌胃;饮食治疗组在喂饲高脂饲料13wk后改为普通饲料喂养.12wk末处死正常组、模型Ⅰ组、中药治疗Ⅰ组大鼠;剩余3组大鼠继续喂养至16wk末处死,测定血清转氨酶(ALT、AST),全血谷胱甘肽过氧化物酶(GSH-PX),肝匀浆丙二醛(MDA)含量,超氧化物歧化酶(SOD)活性,总抗氧化能力(T-AOC),一氧化氮(NO),诱导型一氧化氮合酶(iNOS),谷胱甘肽(GSH)水平,观察肝组织学改变.结果:模型组大鼠12wk出现单纯性脂肪肝,16wk发展为脂肪性肝炎.与正常组比,模型组大鼠肝组织脂质过氧化产物MDA含量明显增多(6.45±1.07,8.38±1.32μmol/gvs5.08±0.91μmol/g,P<0.01),而抗氧化物SOD(171±14,148±26kNU/gtvs198±25kNU/gt,P<0.05和P<0.01),GSH(40.8±5.1,35.0±9.0mg/gvs48.5±7.6mg/g,P<0.05和P<0.01),GSH-PX(11.2±1.5,10.3±1.8μmol/Lvs16.4±3.7μmol/L,P<0.01)含量明显降低,且肝脏的脂肪变性严重程度随着高脂饮食喂养的时间延长而加剧.中药治疗组各项指标较模型组有明显改善(P<0.05或P<0.01),脂肪变性程度明显减轻.而饮食治疗组大鼠肝脏病理学仍呈轻-中度脂肪变性,各项指标与模型组比无显著差异.结论:氧应激和脂质过氧化在NASH形成中发挥重要作用,复方中药通过抗脂质过氧化等作用来治疗大鼠NASH.

AIM： To explore the action of oxygen stress and lipid peroxidation in the establishment of steatohepatitis and the action mechanisms of compound from Chinese medicine （CCM） in the treatment of steatohepatitis in rats fed by high-fat diets. METHODS： Sixty male Sprague Dawley rats were randomly assigned into 6 groups. The rats fed by normal food served as the controls. The rats in model groups （Ⅰ, Ⅱ） were fed with high-fat diets, and those in medication Ⅰ and Ⅱ group were given CCM 9 and 13 wk after high-fat diets feeding. The rats in diet therapeutic group were fed with normal food 13 wk after high-fat diet feeding. The animal in control, model Ⅰ, and medication Ⅰ group were killed at 12 wk, and the rest ones were killed at 16 wk. Blood sample were collected for the detection of serum aspartate transaminase （AST）, alanine aminotransferase （ALT）, and glutathione perioxidase （GSH-PX）, and liver tissues were obtained for the detection of malondialdehyde （MDA） contents, superoxide dismutase （SOD） activity, total antioxidative capacity （TAOC）, nitric exide （NO）, inducible nitric oxide synthase （iNOS） and glutathione （GSH） levels. The histological changes were observed under light microscope. RESULTS： Pure fatty liver was formed in the model rats at 12, and fatty hepatitis was established at 16 wk. In comparison with those of normal rats, the contents of MDA were increased （6.45±1.07, 8.38±1.32 μmol/g vs 5.08±0.91 μmol/g, P 〈0.01） but anti-oxide SOD （171±14, 148±26 kNU/gt vs 198±25 kNU/gt, P 〈0.05 and P 〈0.01 ）, GSH （40.8±5.1,35.0±9.0 mg/g vs 48.5±7.6 mg/g, P 〈0.05 and P 〈0.01）, GSH-PX （11.2±1.5, 10.3±1.8 μmol/L vs 16.4±3.7 μmol/L, P 〈0.01） contents were decreased significantly. The severity degree of hepatic fatty degeneration aggravated with the prolonging of the high-fat diet given time. In comparison with those of model rats, the markers such as MDA, SOD, GSH, and GSH-PX etc. were all significantly improved in the medication rats （P 〈0.05 or P 〈0.01）, and the degree of fatty degeneration was also alleviated. Light or moderate fatty degeneration was observed in diet therapeutic rats, and the relative markers were not notably different from those of model group. CONCLUSION： Oxygen stress and lipid peroxidation play a key role in the establishment of nonalcoholic steatohepatitis in rats, and the compound of Chinese medince has therapeutic effect on nonalcoholic steatohepatitis by anti-lipid peroxidation.