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褪黑素抑制糖尿病大鼠下丘脑-垂体-肾上腺轴功能
夏凌1,张春阳2,刘志民1
0
(1.第二军医大学长征医院内分泌科,上海 200003;2.同济大学附属同济医院内分泌科,上海 200065)
摘要:
目的:观察抗氧化剂褪黑素对糖尿病大鼠氧化应激指标及下丘脑垂体肾上腺轴功能的影响,探讨褪黑素对糖尿病大鼠保护作用的可能机制。方法:雄性SD大鼠随机分为正常对照组(n=6)、糖尿病组(DM,n=7)、糖尿病褪黑素治疗1组(DM+Mel1,n=6)和糖尿病褪黑素治疗2组(DM+Mel2,n=6)。腹腔注射链脲佐菌素(65 mg/kg)制备糖尿病大鼠模型,DM+Mel1组给予10 mg/kg褪黑素灌胃,DM+Mel2组给予0.2 mg/kg褪黑素灌胃,正常对照组和DM组每天灌胃等体积的2%乙醇溶液。12周后检测各组大鼠血糖、体质量、双侧肾上腺质量/体质量值,比色法检测血丙二醇(MDA)含量,酶学法检测血总胆固醇(TC)、三酰甘油(TG)含量,放射免疫法检测血促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)含量。结果:与正常对照组相比,DM组大鼠血糖水平、双侧肾上腺质量/体质量、MDA、TC、TG 、CRH、ACTH、CORT水平显著升高(P<0.01),体质量明显减轻(P<0.01);与DM组相比,DM+Mel1组和DM+Mel2组大鼠血糖、双侧肾上腺质量/体质量、MDA、TC、TG显著降低(P<0.01 或P<0.05),体质量明显升高(P<0.01或P<0.05),DM+Mel1组大鼠血CRH、ACTH、CORT水平显著降低(P<0.01),DM+Mel2组大鼠血CORT水平显著降低(P<0.05),DM+Mel2组大鼠血CRH、ACTH水平没有明显改变。结论:褪黑素可以降低糖尿病大鼠氧化应激水平,改善糖、脂肪代谢紊乱,抑制下丘脑垂体肾上腺轴功能,对实验性糖尿病具有保护作用。
关键词:  褪黑激素  糖尿病,实验性  下丘脑-垂体-肾上腺轴
DOI:10.3724/SP.J.1008.2007.01184
投稿时间:2007-05-25
基金项目:国家重点基础研究规划(“973”计划)(2005CB523304).
Melatonin inhibits the regulation of hypothalamo-pituitary-adrenal axis in diabetic rats
XIA Ling1,ZHANG Chun-yang2,LIU Zhi-min1*
(1.Department of Endocrinology,Changzheng Hospital,Second Military Medical University,Shanghai 200003,China;2. Department of Endocrinology,Tongji Hospital,Tongji University,Shanghai 200065)
Abstract:
Objective:To study the effect of melatonin (Mel),a potent antioxidant,on the oxidative stress and the activity of hypothalamopituitaryadrenal axis in diabetic rats. Methods: Male SD rats were assigned to the following 4 groups:normal control (treated with 2% ethyl alcohol lavage\[NC,n=6\]),diabetes mellitus control (treated with 2% ethyl alcohol lavage \[DM,n=7\]),diabetes mellitus model group 1 (treated with Mel lavage \[10 mg·kg-1·d-1,DM+Mel1,n=6\]), diabetes mellitus model group 2 (treated with Mel lavage \[0.2 mg·kg-1·d-1,DM+Mel2,n=6\]).Diabetes in DM group, DM+Mel1 group and DM+Mel2 group was induced by intraperitoneal injection of streptozotacin(65 mg/kg).Blood glucose,body weight and adrenal gland weight/body weight(AW/BW) were determined in the 4 groups 12 weeks later;malondialdehyde(MDA) was examined with visible spectrophotometry; blood total cholesterol (TC)and triglyceride(TG) were examined with enzymology method; blood corticotrophinreleasing hormone(CRH),adrenocorticotrophic hormone(ACTH) and corticosterone(CORT) were examined with radioimmune method. Results: Blood glucose, MDA , TC, TG,CRH,ACTH,CORT and AW/BW in DM group were significantly higher than those in NC group(P<0.01); and the body weight of rats in DM group were significantly lower those of NC group(P<0.01). Compared with DM group, DM+Mel1 and DM+Mel2 group had a significantly lower blood glucose, MDA ,TC,TG and AW/BW (P<0.01 or P<0.05) and higher body weight (P<0.01). Blood CRH,ACTH and CORT were markedly decreased in DM+Mel1 group(P<0.01); blood CORT were markedly decreased in DM+Mel2 group (P<0.05); blood CRH and ACTH in DM+Mel2 group had no significant changes. Conclusion: Mel may lower the oxidase activity, improve metabolic disorder of glucose and fat, and inhibit the activity of hypothalamopituitaryadrenal axis in diabetic rats, exerting protective effect on diabetic rats.
Key words:  melatonin  diabetes mellitus,experimental  hypothalamo-pituitary-adrenal axis