| Objective: Gastrointestinal motility disturbance is one of the most common complications of severe head injury (SHI) characterized by increased gastric retention, reflux, abdominal distension, diarrhea and vomiting etc. It may lead to enterogenic infection, aspiration pneumonitis and multi-organ functional disturbance and increased mortality. This study aimed at discussing the effect of Hexiangzhengqi Liquid, a Chinese herbal medicine in combination with the enteral nutrition on gastrointestinal motility disturbance and the related change in gastrointestinal peptide in SHI rats so as to provide experimental evidences for the practice of enteral nutrition therapy in the clinic.Methods: The SHI model was established in rats by local impact injury. A total of 108 rats were randomly divided into 5 groups: sham operation group (SO group, n=24), severe head injury group (SHI group, n=24), early enteral nutrition group (EEN group, n=24), enteral nutrition plus Hexiangzhengqi liquid group (ENH group, n=18) and enteral nutrition and mosapride group (ENM group, n=18). SO group was treated with fenestration in left copular part yet without head injury and fed with enteral nutrition and Sodium Chloride with dosage and feeding frequency similar to those in the EEN group; SHI group was fed with Sodium Chloride liquid after head injury with dosage and feeding frequency also similar to those in the EEN group and intragastrically administered with Sodium Chloride liquid 10ml/kg bid; EEN group was fed with early enteral nutrition 6 times/day and intragastrically administered with Sodium Chloride liquid 10ml/kg bid; ENH group was intragastrically administered with Hexiangzhengqi liquid 10ml/kg bid in combination with enteral nutrition; ENM group was intragastrically administered with mosapride liquid (at a daily dose of 5×10-2mg/ml) 10ml/kg bid in combination with enteral nutrition. The main outcomes measures for SO group, SHI group and EEN group were observed at 6h, 24h, 48h and 72h after injury, and which were observed at 24h, 48h and 72h for ENH group and ENM group. The gastric emptying and bowel transit rates were determined by staining method with dextran blue-2000 using as gastrointestinal internal marker, and levels of motilin (MTL) and calcitonin gene-related peptide (CGRP) in plasma, sinus ventriculi, and jejunum were determined by radioimmunoassay (RIA). All of the data are presented as mean value±SD ( x±s). The one-factor analysis of variance was performed with the aid of SPSS10.0 statistical package, with P<0.05 considered as significant and P<0.01 as highly significant.Results:1. SHI model was established successfullyIn our study, the SHI model was established in rats by local impact injury. The mortality of model reached about 43%. Anatomically and pathologically, the injured rats were characterized by the contusion and laceration of brain, hemorrhage and subdural hematoma etc. HE staining at 24h after injury showed marked hemorrhage in hippocampus area, indicating that the model under study was in conformity with the criteria of SHI.2. Change in rats'gastric emptyingThe relative residual rates of gastric stain in SHI group at different time point were significantly higher than in SO group (P<0.01). In EEN group, the level before 48h was of no significance as compared with SHI group, at 72h, which was significantly lower than in SHI (P<0.01) and close to SO group's level. Levels in ENH group and ENM group at 24h were of no significance but higher than in SO group and lower than in EEN group (P<0.01), after 48h, which were significantly lower than in SHI group (P<0.01) and returned to SO group's level, and which were all lower than in EEN group at 48h (P<0.05) but were of no significance at 72h as compared with EEN group, which indicated a marked delayed gastric emptying occurred at 6h and remained un-returned at 72h. After application of EEN, there was still marked delayed gastric emptying, it didn't return to SO group's level until after 72h. EEN combined Hexiangzhengqi liquid or mosapride could promote the gastric emptying at 24h but with a higher level than in SO group, improve the gastric emptying after 48h and bring it back to SO group's level.3. Change in rats'bowel transitIn SHI group, the bowel transits at different time point were significantly lower than in SO group (P<0.01). In EEN group, the bowel transit before 24h was of no significance as compared with SHI group but was significantly lower than in SO group (P<0.01), which was higher than in SHI group at 48h (P<0.01), and at 72h, which returned to SO group's level. In ENH group and ENM group, at 24h the bowel transits levels were all higher than in SHI group (P<0.01or P<0.05) but were of no significance as compared with SO group, were all higher than in EEN group at 24h and 48h (P<0.01or P<0.05) but were of no significance at 72 as compared with EEN group, which indicated that the bowel transit at 6h after injury was lowered and remained un-returned at 72h. After application of EEN, there was still marked bowel transit delay, but it began to recover at 48h and returned to the level in SO group at 72h. EEN combined Hexiangzhengqi liquid or mosapride could promote the bowel transit at 24h and help it recovery to SO group's level.4.Change in MTL level in rats'plasma and gastrointestinal tissuesMTL levels in plasma, sinus ventriculi and jejunum in rats at different time points after injury were all significantly higher than in SO group (P<0.01or P<0.05). In EEN group, MTL level in plasma, sinus ventriculi and jejunum from 6h to 48h were of no significance as compared with SHI group (P<0.01or P<0.05)., but significantly higher than in SO group (P<0.01or P<0.05)., lower than in SHI group at 72h (P<0.05) and returned to SO group's level. In ENH group and ENM group, MTL levels in sinus ventriculi and jejunum after 24h and plasma MTL levels after 48h were all lower than in SHI group (P<0.01or P<0.05) but recovered to SO group's level, at 24h, plasma MTL levels in both groups were of no significance as compared with SHI group but higher than in SO group and lower than in EEN group (P<0.05), at 24h and 48h, plasma and gastrointestinal MTL levels were lower than in EEN group (P<0.01 or P<0.05), but were of no significance at 72h as compared with EEN group, which was suggestive that plasma and gastrointestinal MTL levels increased from 6h and remained un-recovered at 72h. After application of EEN, plasma and gastrointestinal MTL levels remained high, which didn't return to SO group's level until after 72h. EEN combined Hexiangzhengqi liquid or mosapride could help bring down MTL level in gastrointestinal tissues to SO group's level at 24h, but plasma MTL levels in the two groups at 24h were still high yet lower than in EEN group, and which returned to SO group's level at 48h.5. Change in CGRP level in plasma and gastrointestinal tissues of ratsCGRP level in plasma, sinus ventriculi and jejunum in SHI rats at different time points were all significantly higher than in SO group (P<0.01). In EEN group, from 6h to 48h, CGRP levels in jejunum were of no significance as compared with SHI group but were significantly higher than in SO group (P<0.01or P<0.05), which returned to SO group's level at 72h, and CGRP level in plasma and jejunum at 48h were significantly lower than in SHI group (P<0.01) and began to return to SO group's level. In ENH group and ENM group, plasma and gastrointestinal CGRP levels at 24h were lower than in SHI group (P<0.01) and recovered to SO group's level, and CGRP levels in plasma and sinus ventriculi at 24h and 48h and those in jejunum at 24h were lower than in EEN group (P<0.01) but were of no significance as compared with EEN group thereafter, which indicated that plasma and gastrointestinal CGRP levels increased at 6h and remained un-returned at 72h. After application of EEN, plasma and gastrointestinal CGRP levels were still high, but lowered at 48h (CGRP level in jejunum had returned to SO group's level), at 72, levels in all all the three had recovered to SO group's level. EEN combined Hexiangzhengqi liquid or mosapride could help bring down CGRP level to SO group's level at 24h.Conclusion:1. At 6h after SHI, conditions like delayed gastric emptying, slow bowel transit, increased levels of MTL and CGRP in plasma and gastrointestinal tissues may appear, which may lasts more than 72h, thus bringing problems for the practice of enteral nutrition therapy.2. Early enteral nutrition therapy can promote the recovery of gastrointestinal motility to some degree following SHI, gastric emptying and bowel transit showed recovery at 48h and 72 after SHI, this may be related to the effect on levels of MTL and CGRP in plasma and gastrointestinal tissues.3. Enteral nutrition in combination with Hexiangzhengqi liquid can facilitate the improvement of early gastrointestinal motility after SHI, with efficacy equivalent to mosapride, this may be attributed to the regulation on levels of MTL and CGRP in plasma and gastrointestinal tissues. |
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