脾虚证功能性消化不良大鼠胃窦平滑肌CNP-NPRB-cGMP通路改变及四君子汤的干预作用

目的:探讨脾虚证功能性消化不良的发病及四君子汤干预的作用机制。方法:将52只SD大鼠随机分为空白组、模型组、四君子汤组和莫沙必利组,采用碘乙酰胺灌服+小平台站立+饥饱失常法塑造脾虚证功能性消化不良动物模型,随后给予四君子汤6.3 g·kg~(-1)和莫沙必利0.45 mg·kg-1灌胃,每日灌胃给药1次,共14 d,检测大鼠胃排空率,采用酶联免疫吸附测定法(ELISA)检测血清C型钠尿肽(CNP)及胃窦平滑肌组织环磷酸鸟苷(cGMP)含量,蛋白质免疫印迹法(Western blot)检测胃平滑肌B型钠尿肽受体(NPRB)蛋白的表达。结果:与正常组比较,模型组大鼠体重、胃排空率明显下降(P0.05,P0.01),血清CNP含量,平滑肌NPRB蛋白的表达和c GMP含量升高(P0.05,P0.01);与模型组比较,四君子汤和莫沙必利干预后大鼠胃排空率升高(P0.05),血清CNP含量、平滑肌NPRB蛋白的表达量和c GMP含量降低(P0.05,P0.01)。结论:脾虚证功能性消化不良大鼠存在CNP-NPRB-c GMP信号通路改变,四君子汤可能通过调节该信号通路促进胃肠动力。

Disorder in CNP-NPRB-cGMP Pathway of Gastric Antral Smooth Muscle of Functional Dyspepsia Model Rats with Spleen-Deficiency Syndrome and Intervening Mechanism of Sijunzi Tang

Objective: To investigate the pathogenesis of functional dyspepsia with spleen deficiency, and explore the intervening mechanism of Sijunzi Tang. Method: Fifty-two male SD rats were randomly divided into normal group, model group, Sijunzi Tang group and mosapride group. Iodoacetamide gavage method, small platform standing method and hunger disorder method were used to establish the functional dyspepsia rat model with spleen-deficiency. After modeling, Sijunzi Tang (6.3 g·kg^-1) and mosapride (0.45 mg·kg^-1) were given to each intervention group by gavage, once a day, for continuously 14 days. Gastric emptying rate, C-type natriuretic peptide(CNP) and cGMP content were detected by enzyme-linked immunosorbent assay(ELISA), and natriuretic peptide receptor type B(NPR-B) was determined by Western blot. Result: Compared with normal group, weight and gastric emptying rate were lower (P<0.05,P<0.01), CNP content in serum, NPR-B protein expression in gastric antrum smooth muscle, and cGMP content of gastric smooth muscle were higher in model group (P<0.05,P<0.01). Compared with model group, gastric emptying rate was higher (P<0.05), CNP content in serum, NPR-B protein expression in gastric antrum smooth muscle, cGMP content of gastric smooth muscle were lower in Sijunzi Tang group and mosapride group (P<0.05, P<0.01). Conclusion: Functional dyspepsia rats with spleen deficiency show CNP-NPRB-cGMP pathway disorder. Sijunzi Tang may improve gastrointestinal motility by regulating CNP-NPRB-cGMP pathway.