【摘要】 目的研究幽门螺杆菌(Hp)感染对小鼠胃和脊髓神经元表达的影响,探讨Hp感染产生消化不良症状的可能机制。方法建立Hp感染小鼠模型,35只雌性C57BL/6小鼠分为3组急性感染组(感染后2周组,15只)和慢性感染组(感染后12周组,15只),并以生理盐水灌胃的小鼠作为对照(对照组,5只)。小鼠胃黏膜经HE染色和Warthin-Starry染色评估组织学改变和Hp定植密度,经免疫组织化学染色评估胃和脊髓Fos、血管活性肠肽(VIP)及降钙素基因相关肽(CGRP)阳性神经元,并进行比较。结果Hp感染12周时3只小鼠死亡,Hp定植密度明显高于感染2周时,且主要分布在幽门腺黏膜。感染后2周和12周组小鼠幽门腺区、前胃-腺胃交界区及胃体腺区炎症和活动性水平均明显高于对照组,且以感染12周组为重。小鼠胃和脊髓Fos、VIP及CGRP神经元阳性程度(积分)在Hp感染后2周组(15只,分别为胃3.1±1.4、4.5±1.8和2.4±0.8,脊髓3.8±1.2、3.2±1.5和2.2±0.6)和感染后12周组(12只,分别为胃3.1±1.3、3.5±1.6和2.2±0.8;脊髓3.4±0.7、2.6±1.2和2.5±1.1)差异无统计学意义(均P>0.05),但均显著高于对照组(5只,分别为胃2.4±0.9、1.6±0.9和1.2±0.8,脊髓2.0±1.6、1.2±1.1和1.2±1.1,均P<0.05)。结论急性和慢性Hp感染引起小鼠胃黏膜不同程度炎症和活动性等组织学改变,并有胃和脊髓Fos、VIP及CGRP阳性神经元表达显著增加,这可能是Hp阳性消化不良患者症状产生的基础。更多还原

【Abstract】 Objective To investigate the effects of Helicobacter pylori (Hp) infection on neural expression in stomach and spinal cord, and to investigate the mechanism of functional dyspepsia after Hp infection. Methods Thirty-five female C57BL/6 mice were randomly divided into three groups: Group A (acute infection group, undergoing intragastric gavage of Hp suspension every other day for 3 times and then observed for 2 weeks, 15 mice), Group B (chronic infection group, undergoing intragastric gavage of Hp suspension every other day for 3 times and then observed for 2 weeks, 15 mice) and control group (undergoing intragastric gavage of normal saline every other day for 3 times and then observed for 2 weeks, 5 mice). After the observation the mice were killed and their stomachs were taken out to undergo gastric histology and bacterial colonization by HE staining and Warthin-Starry staining respectively. Their spinal cords of thoracic and lumbar segments were taken out too. Immunohistochemistry was used to detect the expression of Fos, vasoactive intestinal polypeptide (VIP), and calcitonin gene-related peptide (CGRP) in the stomach and spinal cord. Results Three mice died 12 weeks after Hp infection. The rate of Hp colonization, mainly localized in pyloric gland region, was greater in Group B than in Group A, and was 0 in the control group. The severity of inflammation as shown by mononuclear cell infiltration, and activity of inflammation as shown by polymorphonuclear cell infiltration, in the pyloric gland region, proventriculus-glandular stomach region, and corpus gland region were more pronounced in Groups A and B, especially in Group B, than in the control group. The expression values of Fos, VIP, and CGRP in the stomach of Group A were 3.1±1.4, 4.5±1.8, and 2.4±0.8 respectively, all not significantly different from those of Group B (3.1±1.3, 3.5±1.6, and 2.2±0.8, all P>0.05). The expression values of Fos, VIP, and CGRP in the spinal cord of Group A were 3.8±1.2, 3.2±1.5, and 2.2±0.6, all not significantly different from those of Group B (3.4±0.7, 2.6±1.2, and 2.5±1.1, all P>0.05 for all). However, the neural expression values in both acute and chronic infection groups were significantly higher than those in the control group (2.4±0.9, 1.6±0.9, and 1.2±0.8 in stomach; and 2.0±1.6, 1.2±1.1, and 1.2±1.1 in spinal cord, P<0.05 for all). Conclusion Hp infection, both acute and chronic, induces gastric histological changes such as inflammation and activity, and enhances the Fos, VIP, and CGRP expression in stomach and spinal cord, which can be a basis for symptom generation in dyspeptic patients with Hp infection.更多还原