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外周静脉注射nesfatin-1对肥胖大鼠胃运动的影响

发布时间:2019-03-23 15:31
【摘要】:目的观察外源性nesfatin-1对肥胖大鼠摄食、体重、胃排空率的影响,以及对其外周循环(血清)中NUCB/nesfatin-1浓度水平的影响。利用水囊法和实施荧光定量RT-PCR技术分别观察肥胖大鼠尾静脉注射不同剂量nesfatin-1后,胃内压的变化情况和胃及十二指肠组织NUCB2mRNA的表达差异。探讨nesfatin-1对肥胖大鼠胃运动的影响。方法肥胖大鼠造模成功后,大鼠行颈静脉插管手术,术后大鼠分组,正常及肥胖大鼠注射外源性nesfatin-1(100μg·kg-1),连续颈静脉给药7 d,期间记录各组大鼠摄食量以及体重,给药结束后采用酚红灌胃法测定大鼠胃排空率。大鼠各个时间点内眦取血并分离血清,再使用ELISA方法检测各组大鼠各时间点血清中NUCB2/nesfatin-1的浓度。使用自制水囊插至大鼠胃中,另一端通过压力传感器连接Larbchart生理记录仪,随后尾静脉注射nesfatin-1,连续观察6-8个小时,并记录大鼠胃压力变化间接地反映出的胃运动变化。结果用高脂饲料连续饲养大鼠8周,正常对照组和正常治疗组大鼠的Lee’s指数分别为314.22和314.44,肥胖对照组和肥胖治疗组大鼠的Lee’s指数分别为318.22和319.03,差异存在显著性(T-test,P0.01),造模成功。连续给药7 d后,给药组摄食量和体重与对照组相比明显降低,但肥胖给药组摄食量及体重下降较正常给药组更加明显。胃排空率与胃排出酚红量是成负相关的,实验中正常对照组和正常治疗组的胃排空率分别是64.71±4.51和46.47±3.20,而肥胖对照组和肥胖治疗组大鼠的胃排空率分别是75.67±2.47和50.88±3.07。肥胖大鼠外周循环(血清)中NUCB2/nesfatin-1的浓度水平显著高于正常大鼠外周循环(血清)中NUCB2/nesfatin-1的浓度水平。肥胖大鼠胃组织NUCB2mRNA的表达显著高于正常大鼠胃组织NUCB2mRNA的表达。肥胖大鼠尾静脉注射外源性nesfatin-1可对其胃运动产生抑制作用。结论综上所述,长期持续外周静脉注射外源性的nesfatin-1可以减轻正常及肥胖大鼠的摄食量和体重,抑制正常及肥胖大鼠的胃排空作用,但对肥胖大鼠作用更加明显。外周较大剂量注射nesfatin-1可显著降低大鼠胃排空作用。大鼠外周循环(血清)中NUCB2/nesfatin-1浓度与Lee’s指数呈正相关性。正常大鼠外周循环NUCB2/nesfatin-1存在昼夜节律性变化。肥胖大鼠外周循环NUCB2/nesfatin-1昼夜节律变化调节紊乱是导致其肥胖的重要原因。大鼠胃NUCB2mRNA的表达与营养代谢状态存在相关性。肥胖大鼠注射外源性nesfatin-1会影响大鼠胃组织内源性NUCB2mRNA的表达。
[Abstract]:Aim to observe the effects of exogenous nesfatin-1 on feeding, body weight, gastric emptying rate and the concentration of NUCB/nesfatin-1 in peripheral circulation (serum) of obese rats. The changes of intragastric pressure and the expression of NUCB2mRNA in stomach and duodenum of obese rats were observed by water bag method and fluorescence quantitative RT-PCR after different doses of nesfatin-1 were injected into tail vein of obese rats respectively. To investigate the effect of nesfatin-1 on gastric motility in obese rats. Methods after successful establishment of obese rats, the rats underwent jugular catheterization. The rats were divided into two groups. Normal and obese rats were injected with exogenous nesfatin-1 (100 渭 g kg-1) for 7 days. The intake and body weight of each group were recorded. The gastric emptying rate was measured by phenol red perfusion method. The blood was collected from the inner canthus of rats at each time point and the serum was separated. Then the concentration of NUCB2/nesfatin-1 in the serum of rats at each time point was detected by ELISA method. A self-made water bag was inserted into the rat stomach, and the other end was connected to the Larbchart physiological recorder through a pressure sensor. Then nesfatin-1, was injected into the tail vein for 6 hours for 8 hours, and the changes of gastric motility indirectly reflected by the changes of the gastric pressure in the rats were recorded. Results the Lee's index of normal control group and normal treatment group were 314.22 and 314.44, respectively, and the Lee's index of obese control group and obesity treated group were 318.22 and 319.03, respectively, when fed with high fat diet for 8 weeks. The difference was significant (T test, P0.01), the model was successful. After 7 days of continuous administration, the intake and body weight of the treatment group were significantly lower than those of the control group, but the weight loss of the obese group was more obvious than that of the normal group. The gastric emptying rate was negatively correlated with the gastric output of phenol red. In the experiment, the gastric emptying rate of the normal control group and the normal treatment group were 64.71 卤4.51 and 46.47 卤3.20, respectively. The gastric emptying rates of obese control group and obesity treatment group were 75.67 卤2.47 and 50.88 卤3.07, respectively. The concentration of NUCB2/nesfatin-1 in the peripheral circulation (serum) of obese rats was significantly higher than that of normal rats (serum), and the concentration of NUCB2/nesfatin-1 in the peripheral circulation (serum) of obese rats was significantly higher than that of normal rats. The expression of NUCB2mRNA in obese rats was significantly higher than that in normal rats. The expression of NUCB2mRNA in obese rats was significantly higher than that in normal rats. Exogenous nesfatin-1 can inhibit gastric motility in obese rats. Conclusion in conclusion, long-term continuous peripheral venous injection of exogenous nesfatin-1 can reduce the intake and body weight of normal and obese rats and inhibit gastric emptying in normal and obese rats, but the effect is more obvious in obese rats. Large peripheral dose of nesfatin-1 could significantly reduce gastric emptying in rats. There was a positive correlation between NUCB2/nesfatin-1 concentration and Lee's index in peripheral circulation (serum) of rats. The circadian rhythmic changes of NUCB2/nesfatin-1 in peripheral circulation were observed in normal rats. The disorder of circadian rhythm of peripheral circulation NUCB2/nesfatin-1 in obese rats is an important cause of obesity. There was a correlation between the expression of gastric NUCB2mRNA and nutritional metabolism in rats. Exogenous nesfatin-1 can affect the expression of endogenous NUCB2mRNA in the stomach of obese rats.
【学位授予单位】:青岛大学
【学位级别】:硕士
【学位授予年份】:2015
【分类号】:R589.2

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