Effect And Mechanism Of Tongxieyaofang On The Rat Model Of Visceral Hypersensitivity

ObjectiveIrritable bowel syndrome(IBS) has become one of the most frequent functional gastrointestinal disorders. The incidence of IBS involves many aspects. The cause and pathogenesis of IBS is not yet expounded until now. Some researches indicate that IBS is a multi-cause and heterogenic disease which is different individual. At present we thought that visceral hypersensitivity is one of IBS most important pathophysiological characteristics, which is the foundation and reason for symptom diversification of the IBS patients.Now there is not any kind of medicine or monotherapy fully good for IBS. Multi-target, integrity effect and few side effects are superiority of traditional Chinese medicine(TCM). The clinical reports showed that curative effect of TCM was superior. TXYF is a typical decoction of TCM, and it is mainly used to cure"diarrhea involves abdominal pain"which is similar to the symptom of IBS. So Tongxieyaofang is widely used in curing IBS, and received well clinical effects.Referring to the experiences on making a rat model of IBS ripely, we has established a rat model of visceral hypersensitivity associated with IBS, based on which we investigated the therapic effects and mechanism of TXYF. The investigation could not only provide a experimental proof of guiding clinical medication of IBS, but also conduce to exploit and manufacture the typical decoctions of TCM.Methods: This article is composed of three parts.PART ONE: Establishment and evaluation of a visceral hypersensitivity rat model of IBS.A visceral hypersensitivity rat model of IBS was manufactured by acetic acid chronic stimulation in colon. Childhood rats were randomly divided into two groups. The rats of model group were stimulated by intrarectal administration of acetic acid daily between postnatal 8 and 21 days, while the control one were stimulated by saline instead. The body weight was measured every week. The threshold of abdominal withdrawal reflex(AWR) was evaluated during rectal distension at the second week and forth week after stimulation, in order to confirm the success of rat model.PART TWO: The therapic effects of TXYF on visceral hypersensitivity model rat of IBS.The rat model was established the same as PART ONE. After modeling, rats were randomly divided into five groups: normal control group(A), model group (B), the low-dose TXYF group (C), the high-dose TXYF group (D), the dicetel group (E). Rats of each groups received their two weeks treatments at postnatal 36 days. The threshold of abdominal withdrawal reflex (AWR) was evaluated before and after their administration. Also the stool and its water content was measured to evaluate the therapic effects of TXYF.PRAT THREE: The mechanism of TXYF on IBS.The rat model and their administration was established the same as PART TWO. This part we observed the content of SP and VIP in ileocecal junction, colon and spinal cord by immunohistochemistry, in order to expound the mechanism of TXYF on IBS.ResultsPART ONE: Rats of both groups did not active abnormally and have diarrhea. The threshold of abdomen-uplifting and back-arching and the time of contract of abdomen muscle of model group showed an obvious decrease compared with the normal group at postnatal 35 days and 50 days (P<0.01). It implied that the visceral sensitivity of model group was much higher than normal group, and the hypersensitivity lasted for a long time. The model group was reproduced successfully.PART TWO: The stool of model group was more and softer than normal group in everytime. And the stool water content was higher than normal group. The threshold of abdomen-uplifting and back-arching and the time of contract of abdomen muscle of C group, D group and E group showed an obvious increase compared with the model group at postnatal 50 days (P<0.05 or P<0.01).PART THREE: Model group's mean density of SP and VIP in ileocecal junction and colon and mean density of SP in posterior horn of spinal cord was increased compared with normal group's (P<0.01). Mean density of VIP in posterior horn of spinal cord showed no difference between each group (P>0.05). C group's mean density of SP in posterior horn of spinal cord was decreased (P<0.05), D group's, E group's mean density of SP and VIP in intestine and mean density of SP in posterior horn of spinal cord was decreased compared with model group's (P<0.05或P<0.01).Conclusions1. Visceral hypersensitivity Rat Model of IBS which was manufactured by the acetic acid chronic stimulation in colon is steady, practicable and repeatable, which is a good imitation of IBS patients who have chronic visceral hypersensitivity.2. With the effects of TXYF, the threshold of AWR could be increase, the stool and stool water content could be decreased. The effects of high-dose TXYF are more obvious.3. The express of SP and VIP in intestines and express of SP in spinal cord is abnormal, which implies that SP and VIP both relate to the happening of abnormal gastrointestinal dynamia and visceral hypersensitivity. And the SP can moderate the visceral hypersensitivity on the level of spinal cord.4. This study indicated that high-dose TXYF could decrease the content of SP and VIP in intestine and content of SP in spinal cord. To regulate the secretion of SP and VIP in intestine which could inhibit importation of harm message, decrease the content of SP in spinal cord which could depress the excitability of nerve cells, should be one of the mechanisms of TXYF on visceral hypersensitivity of IBS.