| Purpose:Through observing the effect of He-wei-li-qi-decoction on the gastrointestinal motility in liver depressive type functional dyspepsia rats,and the effects on the expression of Brain Derived Neurotrophic Factor,cAMP-response element binding protein and Dependent Protein Kinase II,go to investigate the possible mechanism of He-wei-li-qi decoction for treating functional dyspepsia of liver depression from the brain-gut-axis.Material and method: Forty Wistar healthy SPF rats(half male and female)were weighted and randomly divided into four groups:blank control group,model control group,He-wei-li-qi-decoction group and domperidone group.After a week of the adaptive feeding,the open-field test and the sucrose test were carried out one by one.Ten rats in blank control were kept away from the model environment for nomal feeding,the remaining three groups of rats were used to establish liver depressive type functional dyspepsia with a modified chronic unpredictable mild stress method for a total of 21 days.During the modeling period,observed and recorded the general conditions of rats such as the state of mind in rats,body weight,fur color,auricle,activity,drinking water,stool frequency and degree of dryness and so on.After modeling,the rats were weighed,and the open-field test and sucrose preference test were carried out.At the time of treatment,the blank control group were reared normally;the model control group was still stimulated daily by stress;at the same time giving the treatment of a concentration of 0.9702g/ml of He-wei-li-qi decoction solution to the He-wei-li-qi decoction group;Domperidone group was given a concentration of 0.297mg/ml domperidone suspension solution for irrigation treatment.The two groups were dosed twice daily for 14 days.After the treatment,the same weight was weighted and open-field experiments and sucrose experiments were performed.At the end of the experiment,the rats were dissected to perfomed the gastric emptying test and intestinal propulsion test to observe gastrointestinal motility.Taking the enzyme-linked immunosorbent assay to detect the content of BDNF in rat hypothalamus,taking Western blot to detect the protein expression of CREB and ?CaMKII in hypothalamus.Results: 1.General status and behavior test index results(1)Before treatment:After a week of the adaptive feeding,there was no significant difference in the general state,body weight and behavioral testing indicators between the day before model making and the difference was not statistically significant(P>0.05).After modeling,the blank control group rats general state is consistent with the rats before modeling,good mental state,hair color soft and smooth,reactive,well-watered and wellbalanced diet,mild stool and odorless.The remaining three groups of rats were in a sluggish state of mind,hair blight is not smooth,hair removal significantly increased,un-responsive,anorexia state of watery,loose stools,cage foul,rats piles bored or tired lying on the side,the spirit was tension extremely,easy to surprise,sucrose preference rate and behavioral scores have declined.(2)After intervention:the rats in the two intervented groups turned their mental state from sluggish to well gradually,the hair became white gradually,changed from yellow to smooth,activity gradually increased,the diet and drinking water returned to normal gradually,the spirit tended to be alleviated,and the fecal dryness was moderate,sucrose preference rate and behavioral scores have risen,may tend to the blank control group level.2.Gastric residual rate and intestinal propulsion rate:Compared with the blank control group,the gastric residual rate in the model control group was significantly increased,and the small intestine propulsion rate was significantly decreased(P<0.05).Compared with the model control group,the gastric residual rate was significantly decreased and the small intestine propulsion rate was significantly increased in He-wei-li-qi decoction group and domperidone group(P<0.05).There was no significant difference in gastric residual rate and intestinal propulsion rate among blank control group,He-wei-li-qi decoction group and domperidone group(P>0.05).3.Western blot results of each group test(1)Hippocampal ?CaMKII expression level:Compared with the blank control group,the content of ?CaMKII protein in the hypothalamus of the model control group was significantly increased,the difference was statistically significant(P<0.05).Compared with the model control group,the content of ?CaMKII protein in hypothalamus of He-wei-li-qi decoction group decreased significantly(P<0.05).The content of ?CaMKII in hypothalamus of the morphine group was slightly lower than that of the He-wei-li-qi decoction group,with significant difference(P<0.05).There was no significant difference between the blank control group and the He-wei-li-qi decoction group(P>0.05).(2)Hippocampal CREB expression levels:Compared with the blank control group,the level of CREB in the hippocampus of the model control group was significantly lower(P<0.05).Compared with the model control group,the levels of CREB in hippocampal tissue of He-wei-li-qi decoction group were significantly higher than those in model control group(P<0.05).There were no significant differences in CREB levels between the control group and the He-wei-li-qi decoction group and the domperidone group(P>0.05).4.Detection of hypothalamic BDNF by enzyme-linked immunosorbent assay:Compared with the blank control group,the content of BDNF in the hypothalamus of model control group decreased significantly(P<0.05).Compared with the model control group,the content of BDNF in hypothalamus of He-wei-li-qi decoction group and that of domperidone group increased significantly(P<0.05).The content of BDNF in hypothalamus of He-wei-li-qi decoction group was significantly higher than that of the control group(P<0.05),while the difference was statistically significant(P<0.05).Conclusion: 1.By comparing the body mass,sucrose preference rate and behavioral score before and after intervention,it shows that He-wei-li-qi decoction can significantly improve the general mental state of the liver-type functional dyspepsia.2.By comparing the gastric residual rate and intestinal propulsion rate in four groups,the gastric residual rate in He-wei-li-qi decoction group and domperidone group was lower than that in model control group,intestinal propulsion rate was higher than the model control group,and gradually tends to the blank control group;there was no significant difference in gastric emptying and small intestine propulsion between He-wei-li-qi decoction group and domperidone group,which shows that the recipe of "He-wei-li-qi decoction " and "Domperidone" can promote gastrointestinal peristalsis remarkably and can effectively improve a series of gastrointestinal symptoms in functional dyspepsia model rats.3.Through the detection of BDNF in hypothalamus,CREB in hippocampus and ?CaMKII in hypothalamus of rats with functional dyspepsia of liver depression type,it found that compared with the blank control group,the content of BDNF in the hypothalamus of the model control group was significantly decreased,the expression level of CREB in hippocampus was significantly decreased,and the expression level of ?CaMKII in hypothalamus was significantly increased.Studies have shown that the interventions of the He-wei-li-qi decoction and domperidone have a benign regulatory to BDNF in the hypothalamus,CREB in the hippocampus and ?CaMKII in the hypothalamus.It shows that He-wei-li-qi decoction not only can effectively promote gastric motility to relieve dysfunctional gastrointestinal state,but also can treat general mental state of functional dyspepsia of liver depression by effectively relieving the depressive state of rats,it can comprehensively treat this disease in two aspects and it has a good advantage. |
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