Study On The Therapeutic Effect And Mechanism Of Renjiang Jianpi Liqi Decoction On Functional Dyspepsia Rats

AIM:To investigate the therapeutic mechanism of Renzhujianpiliqi formula in a rat model of functional dyspepsia (FD).METHODS:One hundred and thirty 10-day-old male rats were randomly divided into a control group and FD group. FD was induced in rats using 0.1% iodoacetamide by gavage combined clamp tail stimulation. After 8 wk, the FD rats were randomly divided into a model group, a Chinese herbal medicine (CHM) high-dose group, a CHM middle-dose group, a CHM low-dose group and a positive drug group. The control and model groups were treated with 0.9% sodium chloride solution, while the CHM high-, middle-and low-dose groups were orally administered respectively with 1.911, 0.9555 and 0.4775 g/mL modified Renzhujianpiliqi formula for 7 d. Hematoxylin eosin (HE) staining was applied to observe the pathological changes of gastric tissue of the rats. Radioimmunoassay was used to detect the activity of MPO in gastric tissue and MTL, GAS, Ghrelin,5-HT, CGRP conten. The Power lab biological signal collecting system was used to record contractile activity in isolated gastric body longitudinal muscle from rats in the five groups. Real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunohistochemistry were used to detect 5-hydroxytryptamine (serotonin) 4 receptor (5-HT4R) expression in FD and control rats.RESULTS:1 Changes of body weight of rats during modeling period:The growth rate of body weight in model group immature rats were significantly lower than that in control group (P<0.01, P<0.05).2 Changes of MPO activity in gastric tissue of rats during modeling: On the first day after modeling and 8 weeks of age, the MPO activity in gastric tissue of the control group and model group rats compared with no significant difference(P>0.05).3 Changes of gastric mucosa during modeling:At the first day after modeling, gastric mucosal glands normal arrangement in the modeling group immature rats, gland surface can be seen only a small amount of chronic inflammatory cell infiltration, there was no more abnormal. At the age of 8 weeks, there was no any pathological changes of gastric tissue in rats.4 Changes of gastric emptying of rats after modeling:After modeling the food intake during 3 hours, gastric content 3h post food intake in the model group rats were significantly lower than those in the control group(P<0.05), and the food in the stomach remnant was significantly higher than the control group after 3-hour period(P<0.05).5 Changes of body weight of rats during dosing period:The body weight of rats in each group increased, body weight increased’slower in the model group than the other groups. The body weight growth rate of the model group were significantly lower than that in the control group at the sixth and seventh of administertion (P<0.01). Administered for seventh days, the body weight growth rate of CHM in each dosage group and positive drug group rats were significantly higher than that in the model group(P<0.05). There was no significant difference between the CHM and control groups (P>0.05).6 Changes of gastric emptying after administration:High-dose of CHM group and positive drug group rats consumed more solid food than the model group and presented a higher gastric emptying rate over 3-hour period (P<0.05), and the food in the stomach remnant was significantly lower than the model group after 3-hour period(P<0.05). There was no significant difference between the CHM and control groups(P>0.05).7 Changes in MTL, GAS, Ghrelin,5-HT and CGRP of different groups after administration:CHM group and positive drug group increased the content of MTL, GAS, Ghrelin,5-HT in serum of FD rats in different degrees (P<0.05, P<0.01), There was no significant difference between the High-dose of CHM group and positive drug group(P>0.05). CHM group and positive drug group decreaed the content of CGRP in the serum of FD rats differently(P<0.05), there was no significant difference between the high-dose of CHM group and positive drug group(P>0.05).8 Changes in isolated gastric longitudinal smooth muscle contraction after administration:Contraction of isolated gastric smooth muscle showed significantly higher systolic frequency and amplitude in the CHM groups compared with the model group (P<0.01). There was no significant difference between the CHM and control groups (P>0.05).9 Changes in 5-HT4R protein expression in the gastric body longitudinal muscle strips of different groups after administration: Western blotting and immunohistochemistry showed that 5-HT4R protein levels in the CHM groups were significantly higher than those in the model group (P<0.01). There was no significant difference between the CHM and control groups (P>0.05).10 Changes in 5-HT4R mRNA expression in the gastric body longitudinal smooth muscle of different groups after administration:RT-PCR showed that 5-HT4R mRNA levels were significantly higher in the CHM groups compared with the model group (P<0.01). There was no significant difference between the CHM and control groups (P>0.05).CONCLUSION:Renzhujianpiliqi formula promotes gastric motility in iodoacetamide by gavage combined clamp tail stimulation-induced FD in rats, and the underlying mechanism might involve the increase of the MTL, GAS, Ghrelin,5-HT content, the decrease of CGRP content and the upregulation of 5-HT4R mRNA and protein levels.