六味地黄丸对NAFLD大鼠肝脏组织SOD、MDA、TG和TC的影响及意义

Liuwei Dihuangwan protects against non-alcoholic fatty liver disease in rats

目的:探讨六味地黄丸对非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)大鼠肝脏组织超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malonaldehyde,MDA)、甘油三酯(triglyceride,TG)和总胆固醇(total cholesterol,TC)水平的影响,并分析其对肝脏组织的保护作用及机制.方法:按照数字随机分组法将45只大鼠均分为正常组、模型组和六味地黄丸组3组,正常组大鼠使用普通基础饲料喂养,模型组大鼠使用高脂饲料喂养,六味地黄丸组大鼠使用高脂饲料+六味地黄丸喂养,比较3组大鼠血清高密度脂蛋白胆固醇(highdensity lipoproteincholesterol,HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、谷草转氨酶(aspartate transaminase,AST)、谷丙转氨酶(altalanine aminotransferase,ALT)、白蛋白(albumin,ALB)、总蛋白(total protein,TP)、球蛋白(globulose,GLB)水平和肝组织SOD、MDA、TG和总胆固醇(total cholesterol,TC).结果:模型组大鼠血清HDL-C明显低于正常组大鼠(0.61 mmol/L±0.06 mmol/L vs 1.08mmol/L±0.16 mmol/L),血清LDL-C、ALT明显高于正常大鼠(0.75 mmol/L±0.23 mmol/L vs 0.16 mmol/L±0.05 mmol/L、92.16 U/L±35.56 U/L vs 31.61 U/L±14.69 U/L),差异具有显著性(P<0.05);六味地黄丸组大鼠血清L D L-C和A LT水平均明显低于模型组(0.46mmol/L±0.12 mmol/L vs 0.75 mmol/L±0.23mmol/L、41.88 U/L±12.27 U/L vs 92.16 U/L±35.56 U/L),差异具有显著性(P<0.05);模型组大鼠与正常组大鼠血清ALB、TP和GLB水平比较(18.84 g/L±1.95 g/L vs 20.16 g/L±0.95g/L、43.15 g/L±3.98 g/L vs 42.91 g/L±2.62g/L、24.34 g/L±1.65 g/L vs 22.75 g/L±2.19g/L),差异无统计学意义(P>0.05);六味地黄丸组大鼠血清ALB、TP和GLB水平与模型组大鼠比较(18.83 g/L±3.05 g/L vs 18.84 g/L±1.95 g/L、41.17 g/L±4.84 g/L vs 43.15 g/L±3.98 g/L、22.33 g/L±2.41 g/L vs 24.34 g/L±1.65 g/L),差异无统计学意义(P>0.05);模型组大鼠肝脏组织SOD水平明显低于正常组大鼠(196.22 U/mgprot±25.08 U/mgprot vs 361.25U/mgprot±24.17 U/mgprot),MDA、TG和TC水平明显高于正常组大鼠(3.92 nmol/mgprot±1.21 nmol/mgprot vs 1.34 nmol/mgprot±0.32nmol/mgprot、3.75 mmol/L±0.52 mmol/L vs1.62 mmol/L±0.44 mmol/L、1.75 mmol/L±0.65 mmol/L vs 1.05 mmol/L±0.28 mmol/L)差异具有显著性(P<0.05);六味地黄丸组大鼠SOD水平明显高于模型组(274.06 U/mgprot±52.11 U/mgprot vs 196.22 U/mgprot±25.08U/mgprot),MDA、TG和TC水平明显低于模型组(1.77 nmol/mgprot±0.53 nmol/mgprot vs 3.92 nmol/mgprot±1.21 nmol/mgprot、2.36 mmol/L±0.51 mmol/L vs 3.75 mmol/L±0.52 mmol/L、1.45 mmol/L±0.44 mmol/L vs1.75 mmol/L±0.65 mmol/L),差异具有显著性(P<0.05).肉眼和光镜检查均可见模型组大鼠较正常组大鼠有明显异常,六味地黄丸组大鼠较模型组大鼠有明显改善.结论:六味地黄丸能够有效改善高脂饮食诱发的非酒精性脂肪肝大鼠肝功能,对肝细胞具有保护作用,可能通过改善SOD、MDA、TG和TC水平治疗非酒精性脂肪肝.

AIM： To explore whether Liuwei Dihuangwan has a protective effect against non-alcoholic fatty liver disease （NAFLD） in rats and the possible mechanisms involved. METHODS： Forty-five rats were randomly di- vided into three groups： a normal control group, a model control group, and a Liuwei Dihuang- wan treated group. The normal control group was fed a normal diet, the model control group was fed a high-fat diet, and the Liuwei Dihuang- wan treated group was fed a high-fat diet ± Liu- wei Dihuangwan. Serum levels of high-density lipoproteincholesterol （HDL-C）, low-density lipoprotein cholesterol （LDL-C）, aspartate trans- aminase （AST）, alanine aminotransferase （ALT）, albumin （ALB）, total protein （TP）, globulose（GLB）, as well as hepatic levels of superoxide dismutase （SOD）, malonaldehyde （MDA）, tri- glyceride （TG）, and total cholesterol （TC） were compared between different groups. RESULTS： Serum levels of HDL-C （0.61 mmol/ L ± 0.06 mmol/L vs 1.08 mmol/L ± 0.16 retool/L） were significantly lower and those of LDL-C and ALT （0.75 U/L ± 0.23 U/L vs 0.16 U/L ± 0.05 U/L; 92.16 U/L ± 35.56 U/L vs 31.61 U/L ± 14.69 U/L） were significantly higher in the model control group than in the normal control group. Serum levels of LDL-C and ALT were significantly lower in the Liuwei Dihuangwan treated group than in the model control group （0.46 mmol/L ± 0.12 mmol/L vs 0.75 mmol/L ± 0.23 mmol/L; 41.88 U/L ± 12.27 U/L vs 92.16 U/L ± 35.56 U/L; P 〈 0.05 for both）. Serum levels of ALB （18.84 g/L ± 1.95 g/L vs 20.16 g/L ± 0.95 g/L）, TP （43.15 g/L ± 3.98 g/L vs 42.91 g/L ± 2.62 g/L） and GLB （24.34 g/L ± 1.65 g/L vs 22.75 g/L 2.19 g/L） had no significant differences between the model control group and the normal control group （P 〉 0.05 for all）, and between the Liuwei Dihuang- wan treated group and the model control group （ALB： 18.83 g/L ± 3.05 g/L vs 18.84 g/L ± 1.95 g/L; TP： 41.17 g/L ± 4.84 g/L vs 43.15 g/L ± 3.98 g/L; GLB： 22.33 g/L ± 2.41 g/L vs 24.34 g/L ± 1.65 g/L; P 〉 0.05 for all）. Hepatic levels of SOD （196.22 U/mgprot ± 25.08 U/mgprot vs 361.25 U/mgprot ± 24.17 U/mgprot） were significantly lower and those of MDA （3.92 nmol/mgprot ± 1.21 nmol/mgprot vs 1.34 nmol/mgprot ± 0.32 nmol/mgprot）, TG （3.75 mmol/L ± 0.52 mmol/ L vs 1.62 mmol/L ± 0.44 mmol/L） and TC （1.75 mmol/L ± 0.65 mmol/L vs 1.05 mmol/L ± 0.28 mmol/L） were significantly higher in the model control group than in the normal control group （P 〈 0.05 for all）. Hepatic levels of SOD （274.06 U/ mgprot ± 52.11 U/mgprot vs 196.22 U/mgprot ± 25.08 U/mgprot） were significantly higher and those of MDA, TG and TC （1.77 nmol/mgprot ± 0.53 nmol/mgprot vs 3.92 nmol/mgprot ± 1.21 nmol/mgprot, 2.36 mmol/L ± 0.51 mmol/L vs 3.75 mmol/L ± 0.52 mmol/L, 1.45 mmol/L ± 0.44mmol/L vs 1.75 mmol/L ± 0.65 mmol/L） were significantly lower in the Liuwei Dihuangwan treated group than in the model control group （P 〈 0.05 for all）. Pathological changes observed by naked eyes and light microscopy were obvious in the model control group compared with the normal control group, and Liuwei Dihuangwan significantly improved these changes. CONCLUSION： Liuwei Dihuangwan has posi- tive therapeutic effects against experimental NAFLD in rats possibly by improving the levels of SOD, MDA, TG and TC.