Veterans Research and Education Foundation, Veterans Affairs Medical Center, Oklahoma City, Oklahoma.
The First Affiliated Hospital of Xi'an Jiaotong University, Shannxi, China.
Am J Physiol Gastrointest Liver Physiol. 2020 Mar 1;318(3):G574-G581. doi: 10.1152/ajpgi.00255.2019. Epub 2020 Jan 27.
Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450-500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: ) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: ) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and ) same as parameter 1 but 25 Hz; ) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; ) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and ) the nitrergic mechanism, -nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: ) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. ) SNS increased the expression of c-fos in the NTS. ) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. ) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway. Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.
胃容纳功能障碍(GA)在各种胃肠道疾病中经常被报道。目前尚无针对治疗 GA 的标准治疗策略。我们探索了骶神经刺激(SNS)对 GA 的可能影响,并在大鼠中发现了一种脊髓传入和迷走传出机制。在一系列实验中,对植入了慢性胃套管和心电图电极的 Sprague-Dawley 大鼠(450-500g)进行了研究:)使用测压设备研究不同参数的 SNS 对胃张力、顺应性和容纳性的影响;两组参数分别进行测试:)5Hz,500µs,10s 开 90s 关;90%运动阈值和)与参数 1 相同,但为 25Hz;)通过检测大脑孤束核(NTS)中的 c-fos 免疫反应(IR)细胞来研究脊髓传入途径的参与;)通过心电图频谱分析检测心率变异性来研究迷走传出活动的参与;)以及)nitrergic 机制,-硝基-L-精氨酸甲酯(l-NAME),一种一氧化氮合酶(NOS)抑制剂,在 5Hz 的 SNS 之前给予。与 sham-SNS 相比:)5Hz 的 SNS 抑制了胃张力,增加了胃顺应性和 GA。刺激频率为 5Hz 和 25Hz 之间没有差异。)SNS 增加了 NTS 中 c-fos 的表达。)SNS 增加了心脏迷走神经传出活动,降低了交感神经迷走神经比值。)l-NAME 阻断了 SNS 的松弛作用。结论:具有一定参数的 SNS 通过脊髓传入和迷走传出途径松弛胃底,改善胃容纳功能。目前,对于 GA 受损尚无足够的医学治疗方法,因为松弛胃底的药物通常会损害胃窦蠕动,从而进一步延迟胃排空,这在功能性消化不良或胃轻瘫患者中很常见。潜在的骶神经刺激治疗的优势在于它通过增强迷走神经活动来改善胃容纳功能,增强的迷走神经活动会导致胃窦蠕动增强,而不是抑制胃窦蠕动。