肠道交感神经在颈动脉窦压力感受器电刺激改善肥胖相关性高血压中的作用

Role of Intestinal Sympathetic Nerve in the Improvement of Obesity-related Hypertension by Carotid Baroreceptor Stimulation

目的探讨肠道交感神经在颈动脉窦压力感受器电刺激(carotid baroreceptor stimulation,CBS)改善肥胖相关性高血压(obesity-related hypertension,OH)中的作用。方法20只雄性SD大鼠随机分为正常对照(C-sham)组、OH假手术(OH-sham)组、OH植入CBS刺激仪(OH-CBS)组、OH腹腔注射6-羟基多巴胺(OH-6-OHDA-sham)组,每组各5只。采用高脂饮食和10%果糖水喂养4周建立OH模型。所有大鼠均在第4周末植入CBS刺激仪,OH-CBS组仪器发放电刺激,OH-sham组、C-sham组和OH-6-OHDA-sham组仪器不发放刺激,OH-6-OHDA-sham组于第6周腹腔注射6-OHDA。每周测量所有大鼠的血压及体质量;12周后,称重内脏脂肪含量,检测血清糖脂代谢指标;取回肠组织,免疫荧光染色法检测酪氨酸羟化酶(tyrosine hydroxylase,TH)、黏糖蛋白2(mucin-2,MUC2)、胞质紧密粘连蛋白1(zonula occludens-1,ZO-1),实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RT-qPCR)检测MUC2、ZO-1和白细胞介素-22(interleukin-22,IL-22)水平。结果与C-sham组比较,OH-sham组的肠道TH过量表达(P<0.05),血压、体质量、内脏脂肪含量、血清低密度脂蛋白、葡萄糖、游离脂肪酸、甘油三酯、总胆固醇明显升高(P<0.05),血清高密度脂蛋白、IL-22、MUC2、ZO-1的表达降低(P<0.05);OH-CBS组和OH-6-OHDA-sham组则明显减少高脂、高糖喂养下的TH过度表达,降低OH大鼠血压、体质量、内脏脂肪含量、血清低密度脂蛋白、葡萄糖、游离脂肪酸、甘油三酯、总胆固醇,升高血清高密度脂蛋白、IL-22、MUC2、ZO-1的表达(P<0.05)。结论肠道交感神经在CBS改善OH中起着重要作用。

Objective To explore the role of intestinal sympathetic nerve in the improvement of obesity-related hypertension(OH)by carotid baroreceptor stimulation(CBS).Methods Twenty male SD rats were randomly divided into four groups:normal control(C-sham)group,OH-sham group,OH-CBS group and OH-6-OHDA-sham group,with 5 rats in each group.The OH model was induced by feeding with high-fat diet and 10%fructose water for 4 weeks.All rats were implanted with CBS stimulator at the end of the 4th week.The OH-CBS group received electrical stimulation,while the OH-sham,C-sham and OH-6-OHDA-sham groups received no stimulation.The OH-6-OHDA-sham group was intraperitoneally injected with 6-OHDA at the 6th week.Blood pressure and body weight of all rats were measured weekly.After 12 weeks,the weight of visceral fat was recorded,and serum glucose and lipid metabolism indexes were detected.Immunofluorescence staining was used to detect tyrosine hydroxylase(TH),mucin-2(MUC2),and zonula occludens-1(ZO-1)in the ileum.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect MUC2,ZO-1 and interleukin-22(IL-22).Results Compared with the C-sham group,the OH-sham group had significant increases in blood pressure,the intestinal TH was overexpressed in OH-sham group(P<0.05),blood pressure,body weight,visceral fat content,serum low-density lipoprotein,glucose,free fatty acid,triglyceride,and total cholesterol were significantly increased(P<0.05),and serum high-density lipoprotein,IL-22,MUC2,and ZO-1 were decreased(P<0.05).The TH overexpression was significantly reduced,the blood pressure,body weight,visceral fat content,serum low-density lipoprotein,glucose,free fatty acid,triglyceride,total cholesterol of OH rats were significantly decreased,the expression of serum high-density lipoprotein,IL-22,MUC2 and ZO-1 were also increased in OH-CBS group and OH-6-OHDA-sham group under high-fat and high-sugar feeding.Conclusion Intestinal sympathetic nerve plays an important role in the improvement of OH by CBS.