| Objective Curcumin is a bioactive composition extracted from the dried rhizomes of Curcuma longa.It has many biological activities such as anti-inflammatory,antioxidation,scavenging free radicals,reducing blood glucose,protecting cardiovascular,anti-tumor and other biological activities.N itric oxide(NO),as a non adrenergic non cholinergic inhibitory neurotransmitter,can relax the smooth muscle of gastrointestine.As an excitatory neurotransmitter in the gastrointestinal tract,Ach can induce the contraction of gastrointestinal smooth muscle.Both of NO and Ach plays an irreplaceable role in the modulation of gastrointestinal motility.Therefore,this study was to explore the mechanism of curcumin promoting gastrointestinal peristalsis through NO and Ach pathways.L-arginine,a precursor of NO,was used to establish the dysfunctional models of gastrointestinal peristalses in mice,to observe and compare the effect of curcumin on NO delayed gastrointestinal emptying in mice.The mechanisms of curcumin on NO delayed gastrointestinal emptying was investigate.Method K unming male mice were randomly divided into 4 groups: Control,curcumin(Cur),L-arginine(L-arg),L-arginine+curcumin(L-arg+cur).There were 9 mice in each group.The mice in the control group were given in tragastric administration of Arabia glue solution,those in the Cur group received intragastric curcumin solution(200mg/kg),once a day for 15d;those in the L-arg group were given in tragastric Arabia glue solution,and those in the combined group were given in tragastric curcumin solution(200mg/kg),once a day for15 d.Starting from day11 of lavage,the mice in theL-arg and combined groups were administrated with L-arg mixed suspension(2g/kg),respectively.After the last administration,mice were fasted for 24 hours and then the gastric emptying was detected by the methods of methylene blue.The mice were dislocated to death,and the stomach of mice were cut out.Then the gastric emptying rates,the content of NO,the activity of nitric oxide synthase(NOS)and the activity of Acetylcholine(AchE)in stomach were detected.The protein and mRNA expression of AchE were further detected by immunofluorescence staining and real time relative quantitative PCR analysis individually.SPSS17.0 statistical software was used for statistical analysis of the data in each group,and the data were compared by ANOVA,factorial design variance analysis and t test.P<0.05 represents the statistically significant.Results Compared with control group,the gastric emptying rates of mice in L-arg group were significantly decreased(F=10.20,P<0.01).Compared with the L-arg group,the gastric emptying rate of mice in the combined group was increased significantly(F=6.39,P<0.05).Compared with control group,the content of NO in L-arg group were significantly increased(F=10.67,P<0.01).Compared with the L-arg group,the content of NO in the combined group were significantly decreased(F=18.47,P<0.01).Compared with control group,the activity of total nitric oxide synthase(TNOS)and inducible nitric oxide synthase(iNOS)in L-arg group were significantly increased(F=23.92,P<0.01;F=6.84 p<0.05).Compared with the L-arg group,the activity of TNOS(F=17.93,P<0.01),iNOS(F=5.18,P<0.05)of mice in the combined group were significantly decreased.Compared with control group,the activity of AchE were significantly decreased,the expression of AchE mRNA and protein was also decreased(P<0.01)in L-arg group.Compared with the L-arg group,the activity of AchE were significantly increased(P<0.01),and the mRN A and protein expression of AchE was also increased(P<0.01)in the combined group.The above indexes in single curcumin group were no significant changes compared with control group(P>0.05).Conclusion The effects of curcumin on improving mice gastric emptying may be through inhibiting the activity of NOS,and then inhibiting the production of exogenous NO in mice stomach.The other way may be through affecting the change of Ach in mice stomach. |