| Objective The purpose of this study was to investigate the effect of curcumin on intestinal peristalsis in mice.The mouse model of intestinal peristalsis disorder was established by intraperitoneal injection of cyclophosphamide.The interstitial cells of Cajal(ICC)specific tyrosine kinase receptor(C-kit)and its specific ligand(Stem Cell Factor,SCF),gap junction protein 43(Connexin 43,Cx43)between ICC and smooth muscle cells were measured in mice duodenum to further explore whether the effect of curcumin are related to changes of signals targeting ICC and intestinal tissue structure in duodenum.Methods Total of forty male healthy Kunming mice were randomly divided into four groups:control group,curcumin group,cyclophosphamide group and curcumin+cyclophosphamide group,with 10 mice in each group.In curcumin group,curcumin(200mg/kg,0.2ml)mixed with Arabic gum suspension was intragastrically administered for12 days,the physiological saline was received by intraperitoneal injection from the 6~thh day to the 12th day,once a day.In cyclophosphamide group,the same amount of Arabic gum suspension was intragastrically administered for 12 days,the cyclophosphamide(100 mg/kg,0.6 ml)was received by intraperitoneal injection from the 6~thh day to the 12~thh day,once a day In curcumin+cyclophosphamide group,curcumin mixed with Arabic gum suspension was intragastrically administered for 12 days,the cyclophosphamide was received by intraperitoneal injection from the 6~thh day to the 12~thh day,once a day.In control group,Arabic gum suspension was intragastrically administered and physiological saline was received by intraperitoneal injection according to the above method.Changes in body weight were recorded before and after the experiment.The mice in each group were fasted for 24 hours before the intestinal propulsion rate testing.Methylene blue suspension(0.8ml,800g/L)was intragastrically administered to mice,which will be sacrificed by cervical dislocation 20 min later.The intestinal propulsion rate was measured in each group.After mice were sacrificed by cervical dislocation,the appropriate amount of duodenal tissue was removed to extract total RNA and protein respectively.The mRNA expression levels of C-kit,SCF and Cx43 were measured by real-time fluorescence quantitative RT-PCR.The expression of C-kit,SCF and Cx43 at protein levels were evaluated by Western blot.At the same time,the deep muscle layer of duodenal tissue was prepared to evaluate the protein changes of C-kit and Cx43 by immunofluorescence.The changes of duodenal histology were also observed by HE staining.Results Compared with the control group,the weight and small intestinal propulsion rate of mice in cyclophosphamide group were decreased significantly(P=0.000).The levels of mRNA(P=0.000)and protein(P=0.000)of C-kit,SCF and Cx43 were decreased obviously.The area of positive expression of C-kit and Cx43 of submucosal deep muscle layer in duodenal tissue showing by immunofluorescence staining were also decreased significantly(P=0.000).The massive infiltration of lymphocytes under the submucous layer in duodenum were mainly observed by HE staining(P=0.000).Compared with cyclophosphamide group,the weight and small intestinal propulsion rate of mice in curcumin+cyclophosphamide group were increased significantly(P=0.000).The levels of mRNA(P=0.001)and protein(P=0.001-0.007)of C-kit,SCF and Cx43were increased significantly.The immunofluorescence staining of submucosal deep muscle layer in duodenal tissue showed that the area of positive expression of C-kit and Cx43 were also increased significantly(P=0.002,0.033).The number of lymphocytes under the submucosa of duodenum were also decreased significantly(P=0.002).Single using of curcumin has no significant effect in normal mice(P=0.576-0.997).Conclusion Curcumin can significantly improve the gastrointestinal peristalsis decreased by cyclophosphamide,and reduce the weight consumption and cachexia of mice.By enhancing the signal of C-kit/SCF and Cx43,curcumin reduces ICC dysfunction and improves the signal transmission between ICC and smooth muscle cells,so as to promote the gastrointestinal peristalsis. |
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