肥胖大鼠血浆中脂肪因子和骨代谢因子的相关性研究

Study on the correlation between plasma adipokines and bone metabolism factors in obese rats

目的 探讨高脂诱导肥胖大鼠血脂、血糖及血浆中脂肪细胞因子水平与骨代谢因子的相关性。方法 5-6周龄Wistar健康雄性大鼠,随机分为普通饲料（对照组）和高脂饲料（实验组）,连续喂养14周,诱导大鼠肥胖模型。分别于第0、4、6、8、10周每组选取8只,空腹麻醉后眼底静脉取血并分离血浆,测定血浆甘油三酯（TG）、总胆固醇（TC）、游离脂肪酸（FFA）、葡萄糖（Glu）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）水平;酶联免疫法测定血浆中肿瘤坏死因子-α（TNF-α）、核因子NF-κB受体活化因子配体（RANKL）、核因子κB受体活化因子（RANK）、瘦素（LPT）及脂联素（APN）水平。结果 喂养4周后,2组大鼠体重差异开始有统计学意义（P〈0.05）,实验组显著高于对照组。至第10周,2组大鼠体重均进入平台期,体重不再增加,但2组差异仍有统计学意义（P〈0.01）,实验组仍高于对照组。实验组大鼠血浆中Glu、FFA、TG、TC、LDL、TNF-α、RANKL、RANK、LPT水平始终高于对照组大鼠,而APN水平低于正常大鼠,差异有统计学意义（P〈0.05）;大鼠血浆中骨代谢因子RANKL与TNF-α、FFA、TG显著正相关（r值分别为0.412、0.270、0.321,P值均〈0.05）,RANK与TNF-α、FFA、TG及LPT显著正相关（r值分别为0.392、0.270、0.326,0.271,P值均〈0.05）。结论 肥胖状态下大鼠血脂代谢紊乱可通过影响脂肪细胞因子APN及LPT水平始动炎症发生,而炎症状态下高水平TNF-α通过影响RANKL及RANK导致骨代谢异常。

Objective To explore the correlations between blood lipids, blood glucose, plasma adipokines levels and bone metabolism factors in obese rats induced by high fat diet. Methods Healthy Wistar male rats aged 5-6 weeks were randomly divided into general diet group （control group） and high fat diet group （experimental group）, all the rats were fed for 14 weeks to establish obese rat model. Eight rats were selected from each group at 0, 4, 6, 8, and 10 weeks, respectively; fundus vein blood specimens were obtained after fasting anesthesia and then plasma was isolated; the levels of plasma triglyceride （TG）, total cholesterol （TC）, free fatty acids （FFA）, glucose （Glu）, low-density lipoprotein （LDL）, and high-density lipoprotein （HDL） were detected; ELISA was used to detect the levels of plasma tumor necrosis factor-α （ TNF-α）, receptor activator of nuclear factor kappa B ligand （ RANKL）, receptor activator of nuclear factor kappa B （RANK） , leptin （LPT） , and adiponectin （APN） . Results After feeding for 4 weeks, there was statistically significant difference in weight between the two groups （P〈0. 05 ） , the weight of rats in experimental group was significantly higher than that in control group. On the tenth week, the weights of rats in the two groups entered into platform stage, which meant no weight gain, but there was still statistically significant difference between the two groups （P〈0.05）, the weight of rats in experimental group was significantly higher than that in control group. The levels of plasma Glu, FFA, TG, TC, LDL, TNF-α, RANKL, RANK, and LPT in experimental group were higher than those in control group, while the level of plasma APN in experimental group was lower than that in control group, there were statistically significant differences （P〈0. 05）; plasma RANKL was significantly positively correlated with TNF-α, FFA, TG （r=0. 412, P〈0. 05; r=0. 270, P〈 0.05 ; r=0. 321, P〈0. 05 ） ; RANK was significantly positively correlated with TNF-α, FFA, TG, and LPT （ r = 0. 392, P〈0. 05 ; r = 0. 270, P〈0. 05 ; r =0. 326, P〈0. 05 ; r = 0. 271, P〈0. 05） . Conclusion The disorder of lipid metabolism can occur through affecting the levels of adipokines APN and LPT to initiate inflammation among obese rats and the high level of TNF-α leads to abnormal bone metabolism by affecting RANKL and RANK.