基于PCR芯片技术探讨脑肠互动角度下肠源性代谢物氧化三甲胺对脾虚高脂血症大鼠脑神经递质受体基因变化影响  

Exploration of the Effect of Intestinal-derived Metabolite TMAO on Brain Neurotransmitter Receptor Gene Changes in Splenic-deficient Hyperlipidemic Rats under the Perspective of Brain-gut Interaction Based on PCR-microarray Technique

作　　者：王琦[1] 冷雪[1] 刘慧慧[1] 曹媛[1] 李阳[1] WANG Qi;LENG Xue;LIU Huihui;CAO Yuan;LI Yang(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847

出　　处：《辽宁中医药大学学报》2025年第3期1-5,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(82104552);辽宁省教育厅基本科研项目(JYTMS20231822)。

摘　　要：目的应用PCR芯片技术探讨肠源性代谢物氧化三甲胺(trimethylamine N-oxide,TMAO)对脾虚高脂血症大鼠脑神经递质受体基因变化的影响,从脑肠轴的角度探讨肠道菌群代谢物TMAO对脾虚高脂血症大鼠脑神经递质的影响靶标。方法将18只健康SD大鼠随机分为正常组、脾虚高脂血症组、TMAO抑制剂3,3-二甲基-1-丁醇(DMB)组,脾虚高脂血症组和DMB组采用高脂饲料+游泳力竭复合方法造模,正常组给予普通饲料,造模12周后,DMB组进行饮水干预,饮用水中加入1%DMB,正常组与脾虚高脂血症组给予正常饮水,干预4周后进行检测。液相色谱-质谱联用仪(LC-MS)检测血浆TMAO含量;尼氏染色检测大鼠脑组织尼氏小体情况;PCR芯片技术检测大鼠脑神经递质相关mRNA基因的变化。结果与正常组比较,脾虚高脂血症大鼠血浆中TMAO含量上升显著(P<0.01),脑组织尼氏小体染色变浅、细胞变大、排列松散;给予DMB后的DMB组上述情况得到了不同程度缓解。PCR芯片共检测了脑组织神经递质受体90种基因的表达,结果显示与正常组比较,脾虚高脂血症组在P值与基因表达差异倍数(log2FC值)的结果中均发生差异的基因有15种,其中上调14种、下调1种;与脾虚高脂血症组比较,DMB组在P值与log2FC值的结果中均发生差异的基因有11种,其中上调1种、下调10种,两个比较组(脾虚高脂血症组/正常组、DMB组/脾虚高脂血症组)中变化差异明显的共同基因为Grm4、Chrna4、Drd2。结论高水平TAMO引起神经递质受体的变化可能与血脂代谢异常变化具有一定的关联性,神经递质受体可能是防治血脂代谢异常疾病的重要作用靶标。Objective To investigate the effect of intestinal metabolite trimethylamine N-oxide(TMAO)on brain neurotransmitter receptor gene changes in rats with spleen deficiency hyperlipidemia by PCR-microarray technique,and to explore the effect of intestinal flora metabolite TMAO on brain neurotransmitter in rats with spleen deficiency hyperlipidemia from the perspective of brain intestinal axis.Methods 18 healthy SD rats were randomly divided into normal group,spleen deficiency hyperlipidemia group and TMAO inhibitor 3,3-dimethyl-1-butanol(DMB)group.The spleen deficiency hyperlipidemia group and DMB group were constructed by high fat diet+swimming exhaustion combined method,and the normal group was given ordinary diet.After 12 weeks of modeling,the DMB group received drinking water intervention.1%DMB was added into drinking water,and normal drinking water was given to the normal group and the spleen deficiency hyperlipidemia group.After 4 weeks of intervention,detection was conducted.Plasma TMAO content was determined by LC-MS.Nissl's staining was used to detect Nissl's bodies in rat brain.The changes of mRNA genes related to neurotransmitters in rat brain were detected by PCR-microarray technique.Results Compared with normal group,the content of TMAO in plasma of rats in the spleen deficiency hyperlipidemia group increased significantly(P<0.01);The staining of Nissl's bodies in rat brain was shallow,and the cells were enlarged and loosely arranged.After the administration of DMB,the above conditions were alleviated to varying degrees in the DMB group.The expression of 90 neurotransmitter receptor genes in brain tissue were detected by PCR-microarray technique.The results showed that there were 15 different genes in the P value and gene expression differential fold(log2FC value)of the spleen deficiency hyperlipidemia group compared with the normal group,among which 14 were up-regulated and 1 was down-regulated.Compared with the spleen deficiency hyperlipidemia group,there were 11 different genes in the P value and log2F

关 键 词：脾虚高脂血症 氧化三甲胺 脑肠互动 神经递质 

分 类 号：R25[医药卫生—中医内科学]