电针对肥胖大鼠脂肪组织白细胞介素6基因启动子区H3K9乙酰化水平的影响

Effects of Electroacupuncture on H3K9 Acetylation Level in Interleukin 6 Gene Promoter of Adipose Tissue in Obese Rats

目的探讨电针治疗肥胖的可能作用机制。方法将70只大鼠随机选10只作为正常组,给予普通饲料喂养,其余给予高脂饲料喂养8周建立肥胖模型。将达到肥胖标准的30只大鼠随机分为模型组、电针组、假电针组,每组10只。电针组取"足三里""中脘""关元""丰隆"穴,连接电针治疗,每周3次,共治疗8周。假电针组取电针组穴位旁约5mm处浅刺并夹持电极,不予通电。正常组和模型组于相同时间内给予抓取固定。记录各组大鼠干预第0、2、4、6、8周时的体重,计算Lee′s指数;实验结束后检测脂肪组织中白细胞介素6(IL-6)和沉默信息调节因子1(SIRT1)蛋白及mRNA表达,并检验IL-6基因启动子区H3K9乙酰化(H3K9ac)程度以及SIRT1和H3K9ac的共表达情况。结果与正常组比较,其余各组大鼠第0、2、4、6、8周Lee′s指数均显著升高,第8周模型组大鼠脂肪组织中SIRT1蛋白及mRNA表达降低,IL-6蛋白及mRNA表达升高,IL-6基因启动子区H3K9ac水平升高(P<0.05);与模型组比较,电针组第6、8周大鼠体重和Lee′s指数均明显下降,脂肪组织中SIRT1蛋白及mRNA表达升高,IL-6蛋白及mRNA表达降低,IL-6基因启动子区H3K9ac水平下降(P<0.05),而假电针组与模型组之间差异无统计学意义(P>0.05)。各组SIRT1和H3K9ac在脂肪组织细胞核中均存在共表达。结论电针能够有效降低肥胖大鼠体重及Lee′s指数,其机制可能与激活脂肪组织中SIRT1表达,降低IL-6基因启动子区H3K9乙酰化程度有关。

Objective To explore the possible mechanism of electroacupuncture in the treatment of obesity.Methods A number of 10 rats from 70 rats were randomly selected as a normal group and given ordinary feed.The rest were given a high-fat diet for 8 weeks to establish an obesity model,and 30 rats that reached the obesity standard were randomly divided into a model group,an electroacupuncture group,and a sham electroacupuncture group,with 10 rats in each group.The electroacupuncture group selected"Zusanli(ST36)","Zhongwan(RN12)","Guanyuan(RN4)","Fenglong(ST40)"and connected them with electroacupuncture for 3 times a week for 8 weeks.In the sham electroacupuncture group,shallow acupuncture was performed about 5 mm away from the acupuncture point of the electroacupuncture group and the electrodes were clamped without electricity.The normal group and the model group were fixed at the same time.The body weight of rats in each group at 0,2,4,6,and 8 weeks of intervention were recorded,and the Lee′s index was caculated.After the experiment,the interleukin 6(IL-6)and silence information regulator 1(SIRT1)protein and mRNA expression were detected,and the degree of H3 K9 acetylation(H3 K9 ac)and the co-expression of SIRT1 and H3 K9 ac in the IL-6 gene promoter region were examined.Results Compared with the normal group,the Lee′s index of rats in the other groups increased significantly at 0,2,4,6,and 8 weeks,and the expression of SIRT1 protein and mRNA in the adipose tissue of rats in the model group decreased at 8 weeks,and the expression of IL-6 protein and mRNA increased,and the level of H3 K9 ac in the promoter region of IL-6 gene increased(P<0.05).Compared with the model group,the body weight and Lee′s index of the rats in the acupuncture group decreased significantly at 6 and 8 weeks.The expression of SIRT1 protein and mRNA in adipose tissue increased,the expression of IL-6 protein and mRNA decreased,and the level of H3 K9 ac in the promoter region of IL-6 gene decreased(P<0.05).There was no statistically significant difference between the sham electroacupuncture group and the model group(P>0.05).SIRT1 and H3 K9 ac were co-expressed in the nucleus of adipose tissue in each group.Conclusion Electro-acupuncture can effectively reduce the weight and Lee′s index of obese rats.The mechanism may be related to activating SIRT1 expression in adipose tissue and reducing the degree of H3 K9 acetylation in the IL-6 gene promoter region.