小脑顶核注射谷氨酸对慢性内脏高敏感大鼠的作用及其机制研究

Effect and Mechanism of Glutamic Acid Injection Into Cerebellar Fastigial Nucleus on Chronic Visceral Hypersensitivity in Rats

背景:小脑顶核(FN)参与对心血管、摄食、呼吸运动、急性胃黏膜损伤等内脏活动的调节,但对内脏高敏感的调节作用及其可能的机制目前尚未完全清楚。目的:探讨小脑FN注射谷氨酸(Glu)对慢性内脏高敏感大鼠的影响及其可能的机制。方法:采用新生期大鼠结直肠扩张(CRD)法制备慢性内脏高敏感模型。8周后,将大鼠分为CRD组、溶剂组(小脑FN注射0.2μL 0.9%Na Cl溶液)、高、中、低剂量Glu组(小脑FN分别注射12、6、3μg Glu)、3-MPA+Glu组(小脑FN注射谷氨酸脱羧酶抑制剂3-MPA后注射12μg Glu)、Bic+Glu组(下丘脑外侧区注射GABA A受体拮抗剂Bic后小脑FN注射12μg Glu)。以痛阈、腹壁回撤反射(AWR)评分和腹外斜肌放电肌电图(EMG)幅度评估内脏敏感性,检测丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果:成功制备慢性内脏高敏感大鼠模型。与CRD组相比,Glu可剂量依赖性地升高痛阈(P<0.05),降低AWR评分和EMG幅度(P<0.05),降低MDA含量(P<0.05),升高SOD活性(P<0.05)。与12μg Glu组相比,3-MPA+Glu组、Bic+Glu组痛阈显著降低(P<0.05),AWR评分和EMG幅度显著升高(P<0.05),MDA含量显著升高(P<0.05),SOD活性显著降低(P<0.05)。结论:小脑FN注射Glu可明显降低大鼠内脏敏感性,其机制可能为FN的Glu在谷氨酸脱羧酶作用下生成GABA,与下丘脑外侧区GABA A受体结合,增强肠黏膜组织的抗氧化能力,从而降低内脏敏感性。

Background:Cerebellar fastigial nucleus(FN)is involved in regulation of visceral activities such as cardiovascular,ingestion,respiratory,and acute gastric mucosal injury,yet it is unclear whether it participates in the regulation of visceral hypersensitivity and what is the possible mechanism.Aims:To investigate the effect and possible mechanism of glutamic acid(Glu)injection into cerebellar FN on chronic visceral hypersensitivity in rats.Methods:Chronic visceral hypersensitivity rat model was established by neonatal colorectal distension(CRD).After 8 weeks,the rats were divided into CRD group,solvent group(0.2μL 0.9%NaCl solution injection into cerebellar FN),high-,medium-,low-dose Glu groups(12,6,3μg Glu injection into cerebellar FN,respectively),3-MPA+Glu group(12μg Glu injection after glutamate decarboxylase inhibitor 3-MPA injection into cerebellar FN),Bic+Glu group(12μg Glu injection into cerebellar FN after GABA A receptor blocker Bic injection into lateral hypothalamic area).Pain threshold,abdominal withdrawal reflex(AWR)score and abdominal external oblique muscle electromyography(EMG)were used to detect visceral sensitivity,and malondialdehyde(MDA)content and superoxide dismutase(SOD)activity were measured.Results:Chronic visceral hypersensitivity rat model was successfully established.Compared with CRD group,pain threshold was significantly increased(P<0.05),AWR score,EMG amplitude,MDA content were significantly decreased(P<0.05),and SOD activity was significantly increased in a dose-dependent manner in Glu group(P<0.05).Compared with 12μg Glu group,pain threshold was significantly decreased(P<0.05),AWR score,EMG amplitude,MDA content were significantly increased(P<0.05),and SOD activity was significantly decreased in 3-MPA+Glu group,Bic+Glu group(P<0.05).Conclusions:Glu injection into cerebellar FN can significantly reduce the visceral sensitivity in rats.The mechanism may be that Glu in cerebellar FN produces GABA via glutamate decarboxylase,and then binding GABA A receptor in lateral hypothalamic area,resulting in increased intestinal mucosal antioxidant capacity,thereby reducing visceral hypersensitivity.