Based Brain-gut Axis To Explore The Gastrointestinal Motility And Brain-gut Peptide Levels In Functional Dyspepsia Rats

Aim: Functional dyspepsia(FD), a common clinically functional gastrointestinal disorder, has a tremendous impact on patients ’ health and lives and consumes a lot of medical resources. Motility disorder is one of the main causes of the disease, and most patients have suffered early satiety and loss of appetite, and so on. FD is related to many factors, and one of the main factors is the parasecretion of the brain-gut peptides in serum and brain-gut axis. Previous studies have found a number of brain-gut peptides in serum and brain-gut axis play a key role in the regulation of gastrointestinal motility. Due to restrictions of materials from human, current research on dysmotility-FD is deficient, and its pathological mechanism is not clear. The aim of the present study was to investigate the levels of multiple brain-gut peptides based on the brain-gut axis in FD rats.Methods: Wistar rats were randomly divided into control and model groups. Bipolar stainless steel electrodes need to be implanted in duodenum and antrum of both two groups. FD model was established by stimulating semi-starvation rats via tail damping. Then, all the electrophysiological activities of gastrointestinal tract were measured, including the slow-wave, spike activity and migrating motor complex(MMC). After the measurement of gastric emptying and intestinal propulsion, the rats were sacrificed and tissues of the antrum, duodenum and hypothalamus were collected. Then levels of multiple brain-gut peptides were detected in serum and tissues of brain-gut axis. The brain-gut peptides include motilin(MTL) and leptin, vasoactive intestinal peptide(VIP), cholecystokinin(CCK), substance p(SP) and neuropeptide Y(NPY).Results: Compared with control group, FD rats showed irritable and aggressive, and their gastrointestinal motility decreased significantly, MMC activity disordered and the phase Ⅲ of MMC disappeared; gastric emptying and intestinal propulsion were significantly declined(P<0.001 and P<0.01), which showed FD rats model was builded. Plasma MTL and SP levels in FD rats were significantly decreased(P<0.001 and P<0.01); while VIP and leptin levels in FD rats serum were significantly increased(P<0.01 and P<0.001). RT-PCR results indicated that antral and duodenal CCK mRNA expression levels were declined(P<0.05 and P<0.001), but hypothalamic CCK mRNA was enhanced(P<0.001); VIP and SP and NPY mRNA levels were significantly raised in tissues of brain-gut axis(P<0.01, P<0.001 or P<0.05). In addition, changes of MTL, leptin and CCK proteins in the above three tissues detected by immunohistochemistry were consistent with the PCR results. Western Blot assay found that leptin and NPY expression levels in antrum and duodenum were consistent with the results of PCR assay.Conclusion:1. FD rats appeared a significant disorder of gastrointestinal motility, including gastric emptying and intestinal propulsion mitigation, disturbance of MMC activity and phase Ⅲ disappearance.2. Abnormal secretion of brain-gut peptides was found in FD rats, for example, MTL and CCK levels which were directly responsible for the regulation of gastrointestinal motility in the gastric antrum and duodenum were decreased and expression of NPY was significantly increased. In addition, SP and VIP levels related to hyperesthesia were significantly increased.3. Dysmotility in FD may result from the comprehensive effects of multiple brain-gut peptides. Therefore, the analysis and detection of brain-gut peptide play an important role in diagnosis and treatment of FD in clinical practice.