Roux-en-Y胃旁路手术对肥胖大鼠脑组织炎症和脂质蓄积的影响
Effect of Roux-en-Y gastric bypass surgery on the inflammation and lipid accumulation of brain tissue in obese rats
-
摘要: 目的:探讨Roux-en-Y胃旁路(RYGB)手术对高脂饮食诱导的肥胖大鼠脑组织炎症和脂质蓄积的影响。方法:将30只4周龄雄性Wistar大鼠随机分为正常饮食组(ND组)、高脂饮食组(HFD组)及高脂饮食且接受RYGB手术组(HFD+RYGB组),各10只。ND组大鼠给予正常饮食,HFD组和HFD+RYGB组给予高脂饮食。饲养16周后,HFD+RYGB组大鼠行RYGB术,ND组和HFD组行假手术。术后ND组继续正常饮食,HFD组和HFD+RYGB组继续高脂饮食,术后第4周处死大鼠,收集血样,ELISA法测定大鼠血清三酰甘油(TG)、胆固醇(TC)和游离脂肪酸(FFA)水平;并取大鼠脑组织,ELISA法检测大鼠脑组织匀浆二酰基甘油(DAG)和FFA及肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1、IL-6水平,免疫组织化学法检测大鼠下丘脑离子钙接头蛋白分子1(Iba-1)和胶质纤维酸性蛋白(GFAP)表达,电镜观察大鼠下丘脑神经元形态学变化。结果:HFD组大鼠血清TG、TC、FFA水平均高于ND组和HFD+RYGB组(P<0.05~P<0.01);HFD+RYGB组FFA水平明显高于ND组(P<0.01),2组TG、TC水平差异均无统计学意义(P>0.05)。HFD组大鼠脑组织DAG、FFA水平均显著高于HFD+RYGB组和ND组(P<0.01);HFD+RYGB组脑组织DAG、FFA水平亦均显著高于ND组(P<0.01)。ND组和HFD+RYGB组大鼠脑组织中TNF-α、IL-1和IL-6水平均显著低于HFD组(P<0.01);HFD+RYGB组TNF-α水平亦明显高于ND组(P<0.01),但2组IL-1和IL-6水平差异均无统计学意义(P>0.05)。免疫组织化学检测显示,HFD组和HFD+RYGB组大鼠下丘脑Iba-1和GFAP阳性星形胶质细胞数量增多,胞体增大,突起增粗变长;与HFD组比较,HFD+RYGB组Iba-1和GFAP阳性表达减少。电镜下可见HFD组大鼠下丘脑神经元线粒体水肿、空泡形成及大量自噬体形成,HFD+RYGB组大鼠下丘脑神经元病变减轻。结论:RYGB可以下调高脂饮食的诱导肥胖大鼠下丘脑脑组织中TNF-α、IL-1、IL-6的表达,减轻下丘脑神经元病变,改善脑组织的炎症状态,降低脑组织中脂质含量。
-
关键词:
- 肥胖 /
- Roux-en-Y胃旁路手术 /
- 炎症 /
- 脂质蓄积 /
- 胶质纤维酸性蛋白
Abstract: Objective:To investigate the effects of Roux-en-Y gastric bypass(RYGB) surgery on the inflammation and lipid accumulation of brain tissue in obese rats induced by high fat diet.Methods:Thirty Wistar rats were randomly divided into the normal diet group(ND group),high-fat diet group(HFD group) and high-fat diet plus RYGB group(HFD plus RYGB group)(10 rats each group).The ND group was treated with the normal diet,and the HFD group and HFD plus RYGB group were treated with high-fat diet.After 16 weeks,the ND group and HFD group were treated with sham operation,and the HFD plus RYGB group was treated with RYGB.After operation,the ND group was continuously treated with the normal diet,and the HFD group and HFD plus RYGB group were continuously treated with high-fat diet.Rats were sacrificed after 4 weeks of operation.The levels of serum triglyceride(TG),total cholesterol(TC) and free fatty acid(FFA) in three groups were detected using ELISA.The levels of diacylglycerol(DAG),FFA,TNF-α,IL-1 and IL-6 in brain tissue of three groups were measured using ELISA.The expressions of Iba-1 and glial fibrillary acidic protein(GFAP) in hypothalamus brain tissue were observed by immunohistochemistry.The neuronal morphology in hypothalamus brain was observed using electron microscope.Results:The levels of serum TG,TC and FFA in HFD group were higher than those in ND group and HFD plus RYGB group(P<0.05 to P<0.01).The level of FFA in HFD plus RYGB group was significantly higher than that in ND group(P<0.01),and the differences of the levels of TG and TC between HFD plus RYGB group and HFD group were not statistically significant(P>0.05).The levels of DAG and FFA in brain tissue of HFD group were significantly higher than those in HFD plus RYGB group and ND group(P<0.01),and the levels of DAG and FFA in brain tissue of HFD plus RYGB group were significantly higher than those in ND group(P<0.01).The levels of TNF-α,IL-1 and IL-6 in brain tissue of ND group and HFD plus RYGB group were significantly lower than those in HFD group(P<0.01).The level of TNF-α in brain tissue of HFD plus RYGB group was significantly higher than that in ND group(P<0.01),but the differences of the levels of IL-1 and IL-6 between HFD plus RYGB group and ND group were not statistically significant(P>0.05).The immunohistochemistry results showed that the number of the Iba-1 and GFAP positive cells increased,cell body enlarged and protuberance thickened and lengthened in hypothalamus of HFD group and HFD plus RYGB group.Compared with the HFD group,the number of Iba-1 and GFAP positive cells in hypothalamus of HFD plus RYGB group decreased.The neuronal mitochondrial edema,vacuole and a large number of autophagosomes were found in HFD group,and the neuronopathy alleviated in hypothalamus under electron microscope.Conclusions:RYGB can down-regulate the expressions of TNF-α,IL-1 and IL-6,alleviate the neuron lesion,improve the inflammatory response and reduce lipid accumulation in hypothalamus tissue of the obese rats induced by high fat diet. -
[1] CHEN F,WANGY,SHAN X,et al.Association between childhood obesity and metabolic syndrome:evidence from a large sample of Chinese children and adolescents[J].PLoS One,2012,7(10):e47380. [2] MANFREDI T,MICAELA I,UMBERTO C.Obesity-related metabolic syndrome and vascular complications[J].Int J Endocrinol,2013,2013:534056. [3] 崔岩,栗红蕊,孙高洁,等.利拉鲁肽对肥胖大鼠体质量、血脂水平和下丘脑炎症通路的影响研究[J].中国药房,2014,25(17):1571. [4] ABDEEN G,LE CW.Mechanism underlying the weight loss and complications of Roux-en-Y gastric bypass.review[J].Obes Surg,2016,26:410. [5] EVERTON C,MARTINHO AG,MURILLO PU,et al.Impact of Roux-en-Y gastric bypass on metabolic syndrome and insulin resistance parameters[J].Diabetes Technol Ther,2014,16(4):262. [6] MUMPHREY MB,PATTERSON LM,ZHENG H,et al.Roux-en-Y gastric bypass surgery increases number but not density of CCK-,GLP-1-,5-HT-,and neurotensin-expressing enteroendocrine cells in rats[J].Neurogastroenterol Motil,2013,25(1):e70. [7] BOTE GB,KORKUT U,MARTIN LY,et al.Surgical models of roux-en-Y gastric bypass surgery and sleeve gastrectomy in rats and mice[J].Nat Protoc,2015,10(3):495. [8] KONSTANTINOS A,JEAN BC,LAURA G,et al.Remodeling of the residual gastric mucosa after Roux-En-Y gastric bypass or vertical sleeve gastrectomy in diet-induced obese rats[J].PLoS One,2015,10(3):e0121414. [9] 牛利.高糖高脂膳食所致的IETM诱发SAD的探讨[D].太原:山西医科大学,2016. [10] YAN Y,SHA YH,YAO GX,et al.Roux-en-Y gastric bypass versus medical treatment for type 2 diabetes mellitus in obese patients:a systematic review and meta-analysis of randomized controlled trials[J].Medicine (Baltimore),2016,95(17):e3462. [11] ZOU JY,ZHANG P,YU HY,et al.Effect of laparoscopic Roux-en-Y gastric bypass surgery on obstructive sleep apnea in a chinese population with obesity and T2DM[J].Obes Surg,2015,25(8):1446. [12] THALER JP,SCHWARTZ MW.Minireview:inflammation and obesity pathogenesis:the hypothalamus heats up[J].Endocrinology,2010,151(9):4109. [13] STREN JE,FILOSA JA.Bidirectional neuro-glial signaling modalities in the ohypothalamus:role in neurohumoral regulation[J].Auton Neurosci,2014,175(4):51. [14] ANDREW PH,SHI QW,MICHELA P,et al.Reductions in hypothalamic Gfap expression,glial cells and α-tanycytes in lean and hypermetabolic Gnasxl-deficient mice[J].Mol Brain,2016,9:39. [15] MICHAEL B.Role of GFAP in CNS injuries[J].Neurosci Lett,2014,565(17):7. [16] LEI J,GAO GY,FENG JF,et al.Glial fibrillary acidic protein as a biomarker in severe traumatic brain injury patients:a prospective cohort study[J].Crit Care,2015,19:362.
计量
- 文章访问数: 3491
- HTML全文浏览量: 377
- PDF下载量: 97
- 被引次数: 0