Zhong L-Y, Yang Z-H, Li X-R, Wang H, Li L
Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Chongwen District, No.6 Tiantan Xili Road Chongwen District 100050 Beijing, China.
Exp Clin Endocrinol Diabetes. 2009 Oct;117(9):463-9. doi: 10.1055/s-0029-1202790. Epub 2009 May 15.
The present study was to determine the protective effects of melatonin (MLT) against the damages of neuroendocrine-immune induced by lipopolysaccharide (LPS) in streptozotocin (STZ)-induced diabetic rats, and to analyze the parameters related to diabetes and oxidative stress. A total of 70 male Sprague-Dawley rats were assigned to this experiment. 10 of rats received STZ intraperitoneally (i.p.) alone as diabetic control; 40 of rats as the Diabetes+LPS received STZ plus LPS i.p. after induction of diabetes with STZ, then assigned to sub-groups as MLT (0.1) (mg), MLT (1) (mg), and Vehicle group, received two doses MLT and vehicle, i.p., respectively, q6 h for 12 h after LPS administration; and the remaining served as normal and LPS control. LPS significantly increased the serum levels of TNF-alpha and IL-6 in normal and diabetic rats; LPS also dramatically increased the plasma concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone. Both 0.1 and 1 mg/kg MLT doses significantly decreased the serum levels of TNF-alpha and IL-6. Significant inhibitory effects of MLT (1 mg/kg) were observed on the plasma concentrations of CRH, ACTH, and corticosterone of the HPA axis. The beneficial effects of MLT, such as the antioxidant activity and maintaining glucose homoeostasis, were also observed in this study, this resulted in a protective effect against the damages caused by LPS in STZ-induced diabetic rats. This finding probably provides a new approach for preventing the undesirable effects of the vicious cycle of hyperglycemia and stress factors such as severe infection in diabetic patients.
本研究旨在确定褪黑素（MLT）对链脲佐菌素（STZ）诱导的糖尿病大鼠中脂多糖（LPS）所致神经内分泌免疫损伤的保护作用，并分析与糖尿病和氧化应激相关的参数。总共70只雄性Sprague-Dawley大鼠被分配到本实验中。10只大鼠单独腹腔注射（i.p.）STZ作为糖尿病对照组；40只大鼠作为糖尿病+LPS组，在STZ诱导糖尿病后腹腔注射STZ加LPS，然后分为亚组，即MLT（0.1）（mg）组、MLT（1）（mg）组和溶剂对照组，在给予LPS后分别腹腔注射两剂MLT和溶剂，每6小时一次，共12小时；其余大鼠作为正常对照组和LPS对照组。LPS显著升高了正常和糖尿病大鼠血清中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的水平；LPS还显著提高了血浆中促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）和皮质酮的浓度。0.1和1 mg/kg的MLT剂量均显著降低了血清中TNF-α和IL-6的水平。观察到MLT（1 mg/kg）对下丘脑-垂体-肾上腺（HPA）轴的CRH、ACTH和皮质酮血浆浓度有显著抑制作用。本研究还观察到MLT的有益作用，如抗氧化活性和维持血糖稳态，这对STZ诱导的糖尿病大鼠中LPS所致损伤具有保护作用。这一发现可能为预防糖尿病患者高血糖和应激因素（如严重感染）恶性循环的不良影响提供了一种新方法。
