奥氮平诱导肥胖大鼠糖脂代谢紊乱对细胞因子和认知功能损伤的影响

目的 观察奥氮平诱导肥胖大鼠糖脂代谢紊乱对脂肪源性细胞因子影响和认知功能损伤实验研究.方法 40只大鼠随机分为对照组和实验组,每组20只.对照组大鼠进行普通饲料喂养,实验组在普通饲粮喂养基础上行奥氮平（1.2 mg·kg-1）灌胃4周建立奥氮平诱导肥胖大鼠模型.采用酶联免疫测定法测定2组大鼠血清中肿瘤坏死因子α（TNF-α）,白细胞介素6（IL-6）和C-反应蛋白（CRP）的含量,生化比色法测定血清葡萄糖（FBS）含量.采用Y-型迷宫观察2组大鼠学习、记忆能力和逃避潜伏期变化.结果 灌胃4周后,与对照组比较,奥氮平组大鼠的体质量、血糖、血脂均显著升高,差异有统计学意义（P＜0.05）;奥氮平组大鼠的血清TNF-α、IL-6和CRP分别为（1.57±0.04） ng/ml、（127.47± 11.38） pg/ml和（2.68±0.06） mg/ml,与对照组比较[（0.59±0.03）ng/ml、（96.58±8.77） pg/ml和（1.86±0.04） mg/ml]有不同程度的升高,差异有统计学意义（P＜0.05）.实验组大鼠电击次数和逃避潜伏期均高于对照组（P＜0.05）.FBS分别与hs-CRP、IL-6和TNF-α呈正相关（r=0.385,0.260,1.280;均P＜0.05）.结论 奥氮平可以导致大鼠糖脂代谢紊乱,血清TNF-α,IL-6和CRP分泌增加,TNF-α、IL-6和CRP浓度变化与FBS水平呈正相关.血糖升高可促进细胞因子细胞毒性作用,导致大鼠认知功能损害.

Effects of glucose metabolic disorder on adipose-derived cytokine and cognitive impairment in olanzapine-induced obese rats

Objective To observe the adipose-derived cytokine changes and aggravate cognitive impairment in olanzapine-induced obese rats caused by glucose metabolic disorder.Methods 20 rats fed with ordinary fodder were used as normal control group,olanzapine group of 20 rats fed with olanzapine（1.2 mg · kg-1） and ordinary fodder for 4 weeks.Successfully established experimental model rats induced by olanzapine after 4 weeks.Serum tumor necrosis factor α（TNF-α）,interleukins 6 （IL-6） and C-reactive protein （CRP） contents were measured by Elisa.Serum glucose contents were determined by biochemical colorimetric method and blood lipid contents determined with automatic biochemical analyzer.Learning,memory capacity and escape latency were detected with Maze test.Results After administration 4 weeks,the levels of body weight,blood glucose and blood lipid in olanzapine group were higher than those in control group.The serum TNF-α（（1.57±0.04） ng/ml）,IL-6（（127.47±11.38） pg/ml） and CRP （（2.68±0.06） mg/ml） in olanzapine group rised,compared with control group （（0.59±0.03） ng/ml,（96.58± 8.77） pg/ml and （1.86±0.04） mg/ml respectively）,the differences were statistically significant（P〈0.05）.Electric shocks and escape latency in olanzapine group were higher than those in control group （P〈0.05）.The FBS had positive correlation with hs-CRP,IL-6 and TNF-α respectively （r=0.385,0.260,1.280; all P〈0.05）.Conclusion Olanzapine can induce metabolic disturbance of blood glucose,blood hpid,and the increase of serum TNF-α,IL-6 and CRP levels in rats.Positive correlation is showed between TNF-of and FBS.Hyperglycemia can promote cell toxicity and leads to cognitive dysfunction in rats.