| BACKGROUNDS AND AIMSMucosal injury is the main pathological change of intestinal diseases such as duodenitis, Crohn's disease, ulcerative colitis and so on. Qi deficiency syndrome of the spleen is common type of these disorders. Replenishing qi to invigorate the spleen (RQIS) is the fundamental rule of treating them. Codonopsispilosu!a(Cp), Astragalus membranaceus(Am), Atractylodes macrocephala (Amc) and Glycyrrhiza vralensis(Gu) were Chinese medicinal herbs mostly used in RQIS. The prescriptions such as Sijunzi decoction, Buzhongyiqi decoction and so on composed of which have significant clinical therapeutic effects on gastrointestinal disorders such as gastritis, peptic ulcer, Crohn's disease, chronic colitis, etc. Pharmacological researches also proved that they had significant preventive and curative effects on gastrointestinal mucosal injury caused by various pathogenic factors.At present, the cellular and molecular mechanisms and the active material basis of Chinese medicinal herbs with the function of RQIS remain poorly elucidated. Most literatures about mocosal repair and protection were limited to the researches on stomach and colon, however the studies about small intestinal mucosal repair remain blank so far. We consider it is possibly associated with their regulatory effects on the proliferation, differentiation and migration of small intestinal crypt cells. Crypt cells are in situ committed stem cells located within the crypts of small intestinal glands. They retain the undifferentiated character and proliferative potency. After injury of the small intestinal mucosal epithelium, crypt cells quickly proliferated and differentiated into mature cells, which migrated rapidly to epithelial surface to cover the wounded mucosa, and therefore maintain mucosal integrity. Proliferation, differentiation and migration of small intestinal crypt cells play critical role in mucosal repair processes and are regulated via a complex mechanism. It was well known that ornithine decarboxylase (ODC) and its catalyzing products polyamines were involved in the expression of a variety of peptides such as gastrointestinal hormones, protooncogenes, growth factorsrelated genes and cytokines, which therefore promoted the proliferation, differentiation and migration of crypt cells and play an essential role in the mucosal repair processes.Small intestinal crypt-like cells line(EEC-6) are derived from neonatal normal rat small intestine and have characteristics of crypt-type epithelial cells as judged by morphological and immunologic criteria, and was developed and characterized by Quaroni et al, which retain the undifferentiated character of epithelial stem cells and could differentiate into mature cells under suitable conditions. The establishment of IEC-6 cells line play a important role in physiological, pathophysiological and pharmacological researches. It also provided a appropriate in vitro model for study on mucosal healing, and were broadly used in the research for cellular, molecular and genetic mechanism of small intestinal mucosal repair by scholars oversea since it's eatablishment.According to above backgrounds, we hypothesized that the possible mechanism of Chinese medicinal herbs with the function of RQIS on gastrointestinal mucosal repair was to promote crypt cells proliferation, differentiation and migration via induction of ODC mRNA transcription, ODC protein expression, ODC activity and polyamines biosynthesis. Based on this hypothesis, in order to screen the main effective components from Chinese medicinal herbs with the function of RQIS correlated to small intestinal mucosal repair and to sum up the regularity of their combinative uses, and thereby to elucidate their cellular and molecular mechanism on small intestinal mucosal repair, the present study, utilizing IEC-6 cells as a experimental object and pharmacological model, was performed to characterize the role of the effective fractions from Cp, Am, Amc and Gu on intestine epithelial cell proliferation, differentiation, migration and...
|
PDF Full Text Request