| Irritable bowel syndrome (IBS) is a intestinal function disorder which has infrequent intestinal physiology structure and Biochemical abnormalities, with recurrent abdominal pain, diarrhea and abnormal defecation traits. Recently, the morbidity rate of irritable bowel syndrome is assuming the trend of escalation, increasingly influencing the life quality of the patients. It has become one of the problems to be solved on the clinical. It is emergent to search for some safe and effective drugs to improve IBS. Changkang formula (CF) is a clinical experience prescription of Traditional Chinese Medicine. It has got satisfied results in the clinical treatment of IBS. However, its specific mechanism is unclear. This thesis aims to investigate the protective effects of CF on IBS and its mechanisms and safety evaluation through in vivo experiments. The concrete research contents go as follows:(l)Mice intestine propulsion dynamics model was established by subcutaneous injection of methyl sulfate neostigmine. After treated with CF traditional extracts and CF modern extracts, we compared phenol red advance rate.(2)The rat model of diarrhea-irritable bowel syndrome (D-IBS) was established by senna free drinking and stress restraining. After the administration we assessed the abdominal withdrawal reflex (AWR). Then the colon tissue was taken and pathological changes were observed by using HE staining. We investigated the content of substance P (SP) in serum and vasoactive intestinal peptide (VIP) in tissue by ELISA.(3)The rat model of visceral hypersensitivity was established by colorectal distention on neonatal rats (8～21 days). After the administration we evaluated the abdominal withdrawal reflex (AWR). Then the colon tissue was taken and pathological changes were observed by using HE staining. We investigated the content of substance P (SP), calcitonin gene related peptide (CGRP) in serum and vasoactive intestinal peptide (VIP), serotonin in tissue by ELISA. The expression of SP in colon tissue was detected by an immunohistochemical staining.(4)Method of the analgesic activity was tested by the method writhing induced by acetic acid in mice. Then we observed and record the number of writhing, calculated for each group of writhing inhibition rate.(5)Mice intestine propulsion dynamics model was established by subcutaneous injection of methyl sulfate neostigmine. A colored marker (phenol red) was employed for the measurement of intestinal transit. Then advance rate of phenol red was calculated.(6)Acute toxicity test of CF was taken by mice. Then we observed the changes of the mice’s body weight, activities and the mortality.(7)Long-term toxicity experiment of CF was taken by rats. Then we observed the changes of the rats’body weight, food intake, coefficient of important organs, hematology, blood biochemistry and histopathological. The results go as follows:(1)Effects of CF traditional extracts and CF modern extracts on mice intestine propulsion dynamics model acted as disincentives. The same dose of CF traditional extracts and CF modern extracts had no significant differences. What is more, the traditional extraction process was much more convenient and lower-cost. It is said that the most appropriate extracting technology was the traditional extraction process.(2)CF could alleviate the D-IBS model rats’ inhibition of growth of body weight, significantly reduce the high sensitivity of model rats and debase AWR, which suggested that CF might have a prevention and cure effect on D-IBS. Preliminary results suggested that the mechanisms might be related to its efficacy to reduce rat model SP content in the blood and increase the content of VIP in colon tissue.(3)CF could reduce AWR of rats model of visceral hypersensitivity significantly, prompted that CF probably played a role of prevention and control of IBS from pluralism and multilayers to improve the visceralgia sensibility. Preliminary results suggested that the mechanisms might be related to its efficacy to inhibit the down-regulation of the content of plasma SP, plasma CGRP and colon VIP, colon 5-HT.(4)CF could inhibit the writhing response in mice, suggesting that CF has a better analgesic effect.(5)CF could inhibit obviously the hyperfunction of intestinal propulsion in mice, suggesting that CF has effects on inhibition of intestinal propulsive.(6)There were no deaths in CF’s Acute toxicity test suggesting that CF has no toxic effects under the dose of 260g·kg-1.(7)Long-term administration led to weight loss of female rats, but comprehensive other detection indexes did not show the drug has obvious toxicity. |
PDF Full Text Request