[Study on the mechanism of acupuncture underlying improvement of functional dyspepsia with depression-like behavior in rats].

Abstract

Objectives: To observe the effect of acupuncture on gastrointestinal motility, synaptic structure, brain-gut peptide and 5-hydroxytryptamine (5-HT) system in rats with functional dyspepsia (FD) and depression, so as to explore its mechanism underlying improvement of FD and depression-like behavior.

Methods: Forty male SD rats were randomly divided into control, model, acupuncture and medication (fluoxetine) groups with 10 rats in each group. The model of FD with depression comorbidity was established by multi-factor stress conditioning (chronic unpredictability stimulation + modified tail-clamp irritation stimulation+intermittent fasting) for 28 d. Acupuncture was applied to "Baihui" (GV20), bilateral "Zusanli"(ST36) and "Zhongwan" (CV12) for 20 min, once daily for 7 d. The rats in the medication group received intraperitoneal injection of fluoxetine (20 mg/kg) once daily for 7 d. The suppression-like behavior was assessed by using tail suspension immobility time in 4 min, forced swimming immobility time in 4 min and sucrose preference rate. The gastrointestinal motility was assessed by using gastric emptying rate and small intestinal propulsion rate. The ultrastructural changes of myelin and synapse in the hippocampus were observed by transmission electron microscope. ELISA was used to detect the contents of serum somatostatin, motilin and 5-HT, and Western blot was used to detect the protein expression levels of tryptophan hydroxylase 1 (TPH1) and 5-hydroxytryptamine receptor 3 (5-HT₃R) in hippocampus.

Results: Compared with the control group, the tail suspension immobility time and forced swimming immobility time were significantly increased (P<0.05), the sucrose preference rate, gastric emptying rate and small intestinal propulsion rate, contents of serum somatostatin, motilin and 5-HT, and the protein expression levels of TPH1 and 5-HT₃R in the hippocampus were significantly decreased (P<0.05) in the model group. In comparison with the model group, the tail suspension immobility time and forced swimming immobility time were significantly decreased (P<0.05), whereas the sucrose preference rate, gastric emptying rate and small intestinal propulsion rate, contents of serum somatostatin, motilin and 5-HT, and the protein expression levels of TPH1 and 5-HT₃R in the hippocampus were significantly increased (P<0.05) in the acupuncture group. Compared with the model group, the changes in behavioral indexes, number of synapses, serum 5-HT content, hippocampal TPH1 and 5-HT₃R protein expression levels in the medication group were same as those in the acupuncture group (P<0.05). Outcomes of transmission electron microscopy displayed that in the model group, the hippocampus had obvious myelin degeneration and lysis, fewer microfilaments and microtubules, blurred mitochondria with loss of a large number of organelles, which was relatively milder in both acupuncture and medication groups. Both acupuncture and medication interventions evidently reversed modeling-induced reduction in the number of hippocampal synapses (P<0.05).

Conclusions: Acupuncture can improve the gastrointestinal motility and hippocampal synaptic damage in rats with FD and depression, which may be related to its functions in up-regulating the levels of brain-gut peptides and 5-HT system.