从改善“脂毒性”看六味地黄丸对自发性糖尿病OLETF大鼠肝脏的保护  

Effects of Liuwei Dihuang Pills on lipid metabolism and the liver structure in spontaneously diabetic OLETF rats

作　　者：李佳[1] 薛耀明[2] 朱波[2] 潘永华[2] 张燕[2] LI Jia;XUE Yaoming;ZHU Bo;PAN Yonghua;ZHANG Yan(Department of Endocrinology,General Hospital of Guangzhou Military Command of PLA;Department of Endocrinology and Metabolism,Nanfang Hospital,Nanfang Medical University,Guangzhou 510515,China)

机构地区：[1]广州军区广州总医院内分泌科,广东广州510010 [2]南方医科大学南方医院内分泌代谢科,广东广州510515

出　　处：《暨南大学学报（自然科学与医学版）》2018年第2期162-168,共7页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：广东省自然科学基金项目(2012040006886)

摘　　要：目的:通过观察六味地黄丸对自发性2型糖尿病OLETF大鼠血清脂代谢指标及肝脏组织学的影响,从改善"脂毒性"角度探讨六味地黄丸通过保护肝脏,预防糖尿病的可能机制.方法:自发性2型糖尿病大鼠OLETF鼠40只,随机分为六味地黄丸干预组和对照组,LETO鼠10只作为正常对照组.干预组从8周龄起每天以质量分数为2.4 mg/kg的六味地黄丸灌胃给药,其余两组以等量清水灌胃.定期口服葡萄糖耐量(OGTT)试验.于8、32和40周龄时分批宰杀大鼠.检测血清甘油三酯、血清胆固醇、血清游离脂肪酸.分离肝脏,HE染色观察肝脏结构组织学变化;苏丹Ⅲ染色观察肝脏脂肪变性程度.结果:干预组的发病率显著低于同时期对照组(P<0.01).LETO组无IGT或糖尿病发生.干预组血清甘油三酯、胆固醇和血清游离脂肪酸显著低于对照组(P<0.05),与LETO组相比无显著性差异(P<0.05).随着糖尿病病程进展,OLETE大鼠肝脏的脂肪浸润呈渐进性加重;经过六味地黄丸干预的糖尿病大鼠肝脏结构保存明显优于对照组.LETO组大鼠肝脏结构随着周龄延长无明显变化.结论:六味地黄丸早期干预能降低糖尿病大鼠糖尿病发病率,改善脂代谢,减少肝脏局部脂肪堆积,减轻肝脏脂毒性,保护肝脏形态,可能是其预防糖尿病的机制之一.Objective:To study the effects of Liuwei Dihuang Pills on diabetes in OLETF(Otsuka Long-Evans Tokushima Fatty)rats,and to explore the probability of Liuwei Dihuang Pills for prevention of diabetes in laboratory animals.Methods:Forty male OLETF rats were divided randomly into Liuwei group(Group Liuwei)and control group(Group Control)(n=20 per group).10 male LETO rats were used as normal control group(Group LETO).Rats of Group Liuwei were given Liuwei Dihuang Pills(2.4 mg·kg-1·d-1)by gavage since age 8 weeks.Blood glucose was determined by OGTT.Rats were sacrificed at 8,32 and 40th weeks and the liver tissue isolated.Serum triglyceride,cholesterol,and free fatty acid(FFA)were determined.The morphological changes of the liver were measured by HE staining and Sudan III staining.Results:During the experiment,structures of the liver in Group Control gradually exhibited evacuation;while there was no significant damages found in the liver of Group Liuwei.After Sudan III staining,at age 32 weeks,obvious steatosis appeared in hepatocytes of Group Control,and the steatosis mainly presented as microvesicular steatosis,while steatosis in Group Liuwei was decreased markedly.At age 40 weeks,both microvesicular and macrovesicular steatosis were observed in the hepatocytes of Group Control,while steatosis was significantly less in Group Liuwei.There was no significant pathological change in the liver of LETO rats.Rats of Group Liuwei developed diabetes since 30 weeks,and the incidence rate was 28.6%at 40 weeks,significantly lower than that of Group Control(P<0.01).Conclusion:Liuwei Dihuang Pills can significantly decrease the incidence rate of diabetes;and in the meantime decrease the serum triglyceride,cholesterol,FFA,and steatosis of hepatocytes.These may be the mechanisms of Liuwei Dihuang Pill in prevention of diabetes.

关 键 词：2型糖尿病 六味地黄丸 OLETF鼠 肝脏 脂毒性 

分 类 号：R587.4[医药卫生—内分泌]