Kondo T, Oshima T, Koseki J, Hattori T, Kase Y, Tomita T, Fukui H, Watari J, Miwa H
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Neurogastroenterol Motil. 2014 Jul;26(7):913-21. doi: 10.1111/nmo.12342. Epub 2014 Apr 9.
While there are reports that the herbal medicine rikkunshito (RKT) relieves upper gastrointestinal disease symptoms, the effect of RKT on primary afferent neurons is unknown.
A model of reflux esophagitis (RE) was implemented using male Wistar rats aged 6-7 weeks. Ten days after surgery, the total area of esophageal mucosal erosion sites was determined. Th8-10 dorsal root ganglia (DRG) were dissected out and the expression of substance P (SP), calcitonin gene-related peptide (CGRP), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was determined in DRG using immunohistochemistry. RKT (0.6%/WV) or omeprazole (OME) (10 mg/kg) was administered for 10 days beginning on the day after surgery. Voluntary movement was measured with an infrared sensor for 22 h each day.
RE rats showed esophageal mucosal erosion and significantly increased number of SP/CGRP- and p-ERK1/2-immunoreactive neurons in DRG. Treatment with OME improved the size of erosive lesions in the esophageal mucosa of RE rats, while RKT did not. Treatment with RKT or OME significantly reduced the expression of SP/CGRP and p-ERK1/2 in DRG, and significantly increased voluntary movement in RE rats.
CONCLUSIONS & INFERENCES: RKT inhibited the activation of ERK1/2 and decreased the expression of SP and CGRP in DRG of RE rats, which may be associated with the observed amelioration of voluntary movement.
虽然有报道称草药六君子汤(RKT)可缓解上消化道疾病症状,但RKT对初级传入神经元的作用尚不清楚。
采用6 - 7周龄雄性Wistar大鼠建立反流性食管炎(RE)模型。手术后10天,测定食管黏膜糜烂部位的总面积。取出Th8 - 10背根神经节(DRG),采用免疫组织化学法测定DRG中P物质(SP)、降钙素基因相关肽(CGRP)和磷酸化细胞外信号调节激酶1/2(p - ERK1/2)的表达。从手术后第二天开始,给予RKT(0.6%/WV)或奥美拉唑(OME)(10 mg/kg),持续10天。每天用红外传感器测量22小时的自主活动。
RE大鼠出现食管黏膜糜烂,DRG中SP/CGRP和p - ERK1/2免疫反应性神经元数量显著增加。OME治疗改善了RE大鼠食管黏膜糜烂病变的大小,而RKT没有。RKT或OME治疗显著降低了DRG中SP/CGRP和p - ERK1/2的表达,并显著增加了RE大鼠的自主活动。
RKT抑制了RE大鼠DRG中ERK1/2的激活,降低了SP和CGRP的表达,这可能与观察到的自主活动改善有关。