摘要
目的研究利拉鲁肽对食源性肥胖大鼠的治疗效果,并探讨其对p38丝裂原活化蛋白激酶(p38 MAPK)信号通路的影响。方法以饲喂高脂饲料的方法建立食源性肥胖大鼠模型。将31只食源性肥胖大鼠随机分为模型组(n=11)、利拉鲁肽组(n=10)、联合组(n=10),另取10只健康大鼠做为对照组。利拉鲁肽组腹腔注射0.6 mg·kg^(-1)利拉鲁肽注射液,联合组腹腔注射0.6 mg·kg^(-1)利拉鲁肽注射液+2 mg·kg^(-1)茴香霉素,对照组、模型组腹腔注射等体积生理盐水。每天1次,持续2周。以全自动生化分析仪检测大鼠血脂指标;以脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)染色检测下丘脑弓状核神经元凋亡率;以蛋白质印迹法检测下丘脑组织p38 MAPK、p-p38 MAPK、细胞外信号调节激酶(ERK1/2)、p-ERK1/2蛋白表达水平。结果利拉鲁肽组、联合组、对照组、模型组的体脂比分别为(3.34±0.35)%、(3.61±0.38)%、(2.38±0.25)%和(3.94±0.41)%;三酰甘油(TG)分别为(1.03±0.09)、(1.19±0.10)、(0.89±0.09)和(1.41±0.13)mmol·L^(-1);下丘脑弓状核神经元凋亡率分别为(16.61±2.53)%、(22.58±2.89)%、(7.56±0.81)%和(29.17±3.14)%;下丘脑p-p38 MAPK/p38 MAPK分别为0.34±0.02、0.52±0.04、0.21±0.01和0.81±0.06;p-ERK1/2/ERK1/2分别为0.19±0.01、0.37±0.03、0.13±0.01和0.45±0.04。上述指标,模型组与对照组比较,利拉鲁肽组与模型组比较,联合组与利拉鲁肽组比较,差异均有统计学意义(均P<0.05)。结论利拉鲁肽可减轻食源性肥胖大鼠体质量及体脂比,降低血脂,减少下丘脑弓状核神经元凋亡,其机制可能与抑制下丘脑p38 MAPK信号通路有关。
Objective To study the therapeutic effect of liraglutide on food-induced obese rats and to explore its effect on the p38 mitogenactivated protein kinase(p38 MAPK)signaling pathway.Methods The rat model of food-borne obesity was established by feeding high fa diet.Thirty-one food-induced obese rats were randomly divided into model group(n=11),liraglutide group(n=10),combined group(n=10),and 10 healthy rats were divided into control group.In the liraglutide group,intraperitoneal injection of liraglutide injection 0.6mg·kg^(-1);combined group intraperitoneal injection of 0.6 mg·kg^(-1)liraglutide injection+2 mg·kg^(-1)anisomycin;the control group and model group were intraperitoneally injected with an equal volume o normal saline.Once a day for two weeks.The blood lipid indexes of rats were detected by automatic biochemical analyzer;the apoptosis rate of hypothalamic arcuate neurons was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL)staining;the protein expressions of p38 MAPK,p-p38 MAPK,extracellular signal-regulated kinase(ERK1/2)and p-ERK1/2 in hypothalamus were detected by Western blotting.Results The body fat ratios of the liraglutide group,combined group,control group and model group were(3.34±0.35)%,(3.61±0.38)%,(2.38±0.25)%and(3.94±0.41)%;the triglycerides(TG)were(1.03±0.09),(1.19±0.10),(0.89±0.09)and(1.41±0.13)mmol·L^(-1);the apoptosis rates of hypothalamic arcuate nucleus neurons were(16.61±2.53)%,(22.58±2.89)%,(7.56±0.81)%and(29.17±3.14)%;the p-p38MAPK/p38 MAPK were 0.34±0.02,0.52±0.04,0.21±0.01 and 0.81±0.06;p-ERK1/2/ERK1/2 were0.19±0.01,0.37±0.03,0.13±0.01 and 0.45±0.04.The above indicators,the differences between the model group and the control group,the liraglutide group and the model group,and the combined group and the liraglutide group were statistically significant(all P<0.05).Conclusion Liraglutide can reduce the body mass and body fat ratio of food-induced obese rats,lower blood lipids,and reduce neuronal apoptosis in the arcuate nucleu
作者
张洁
董闪闪
康岩
周慧敏
贾新菊
ZHANG Jie;DONG Shan-shan;KANG Yan;ZHOU Hui-min;JIA Xin-ju(Department of Endocrinology,The First Hospital of Hebei Medical University,Shijiazhuang 050031,Hebei Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第5期703-707,共5页
The Chinese Journal of Clinical Pharmacology
基金
河北省医学科研研究课题计划基金资助项目(20221381)。
关键词
食源性肥胖
利拉鲁肽
下丘脑弓状核神经元
food-borne obesity
liraglutide
hypothalamic arcuate nucleus neurons
