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OBJECTIVE：To explo re the dose-effect relationship and mechanism of protective effects of total asiaticoside （TA） on gastrointestinal motility and enteric nervous system （ENS）in aged functional dyspepsia （FD）model rats. METHODS ：Aged male SD rats of 16 months old were randomly divided into blank control group ，model group ，TA low dose ，medium dose and high dose groups （15，30，60 mg/kg），with 8 rats in each group. FD model was established by tail-stimulation combined with irregular diet for 4 weeks. The next day after modeling ，administration groups were given relevant doses of TA solution intragastrically ； control group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 15 d. Gastric emptying rate and small intestinal propulsion rate of rats were examined. ELISA were used to detect serum contents of MTL and VIP. Immunofluorescence and immunohistochemistry were proposed to measure the expression of ENS marker （S100β and GDNF）in gastric antrum tissue. The protein expression of S 100β，GFAP，PGP9.5，GDNF，p-MEK and p-ERK 1/2 in gastric antrum tissue were measured by Western blotting assay. RESULTS ：Compared with blank control group ，gastric emptying rate and small intestinal propulsion rate ，serum MTL content and protein expression of PGP 9.5 in gastric antrum tissue of model and TA low，medium dose group were decreased significantly ，while serum VIP content ，protein expressions of S 100β，GFAP，GDNF， p-MEK and p-ERK 1/2 in gastric tissue were increased significantly （P＜0.05）. Compared with model group ，gastric emptying rate and small intestinal propulsion rate of TA groups were increased significantly （P＜0.05）；except for GFAP protein in TA low dose group（P＞0.05），the serum MTL content and the expression of PGP 9.5 protein in gastric antrum tissue of rats in TA groups were increased significantly ，while serum VIP content ，protein expression of S 100β，GFAP，GDNF，p-MEK and p-ERK 1/2 in gastric antrum tissue were decreased significantly （P＜0.05）. Some or most of the content of gastrointestinal motility indexes and related factor protein expression were significantly different among TA groups （P＜0.05），and the indexes in TA high dose group could recover to the levels which were not significantly different with blank control group （P＞0.05）. CONCLUSIONS ：TA can dose-dependently improve the gastrointestinal motility deficiency and ENS dysfunction in aged FD model rats ，especially in high dose（60 mg/kg）of TA group. Its mechanism may be related with promoting the release of endogenous MTL ，inhibiting the secretion of VIP ，expression of GDNF and the activation of downstream signaling pathway ，and promoting the repair of ENS and intestinal neurons.
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Objective To evaluate the efficacy difference between flupentixol and melitracen combined with conventional medicine and conventional drug alone in the treatment of irritable bowel syndrome (IBS).Methods Studies on flupentixol and melitracen combined with conventional medicine (pinaverium bromide and trimebutine maleate) and conventional medicine alone in the treatment of IBS were collected and reviewed through searching the Chinese Academic Journals Full-text Database,Chinese VIP Full-text Database and PubMed database.After that,the test for homogeneity and the combined effect test were estimated. Results A total of 12 clinical studies on flupentixol and melitracen combined with conventional medicine for four to twelve weeks in the treatment of IBS were collected six studies indicated the homogeneity test of flupentixol and melitracen combined with pinaverium bromide (x2 =1.90,df=5,P=0.86,I2 =0).For the fixed-effect model,the odds ratio was 7.92 and 95％ CI was between 4.85 and 12.95,which suggested the combined therapy was better.The other six studies indicated the homogeneity test of flupentixol and melitracen combined with trimebutine maleate (x2 =5.60,df=5,P =0.35,I2 =10.6 ％).For the fixed-effect model,the odds ratio was 5.91 and 95％ CI was between 4.06 and 8.61,which suggested the combined therapy was better.After merging the 12 studies it indicated the homogeneity test of flupentixol and melitracen combined with conventional medicine (x2 =8.40,df =11,P =0.68,I2 =0).For the fixed effect model,the odds ratio was 6.63 and 95％ CI was between 4.92 and 8.93.Conclusion The efficacy of flupentixol and melitracen combined with conventional medicine in the treatment of IBS was better than that of conventional medicine alone,however,still more high quality trials are needed for further confirmation.