Regulatory Mechanism Of Yiqi Jiedu Decoction On Mitochondrial Structure Abnormality And Immune Injury In UC Rats

1. BackgroundUlcerative Colitis (UC) is a kind of peptic diseases with pathological features as chronic inflammation and ulcers on or beneath colonic mucosa. Patients with UC tends to suffer from mucopurulent bloody stools, diarrhea, stomachache and tenesmus. Since the acute stage and inactive stage of UC take places alternatively, UC has become one of the most important researches among medical researchers. The commonest therapy of UC in modern medicine is the anti-inflammatory method, which has been found to be effective during acute stage but lack of lasting effects. According to traditional Chinese medicine, UC a disease with spleen deficiency (DS) in essence with damp-heat and blood stasis, which last during inactive stage of UC, as the symptoms.2. ObjectiveThis paper aims at analyzing a traditional Chinese medicine therapy of UC, the boosting qi and resolving toxin (BQIRT) formula, through randomized controlled experiments on rats with UC. Prescriptions of BQIRT would be used as intervention treatment, hence to analyze the effects and features of BQIRT in different stages of UC and the influences of BQIRT on mitochondrial structures. Thus to reveal the material basis of spleen deficiency and the pathomechanism of repeated attacks. In this way, suggestions can be given for improving clinical effects of BQIRT on UC3. Methods:In the study, rats are randomly categorized into normal group, model group, BQIRT group and mesalazine group. Immunochemical methods would be adopted to form the later three groups. Except for the rats in the normal group, rats in the other groups would be treated by gavage with distilled water, BQIRT prescriptions and mesalazine, respectively. Observation would be conducted before treatment,2 weeks since treatment and 6 weeks since treatment, respectively. The observation involves:(1) general conditions among different groups, variations of disease activity index (DAI) and pathologic changes; (2) changes of ultra-structures on colonic mucosal epithelial cells, changes of mitochondrial structures (evaluated by Flameng method); (3) variations of NO concentrations in the serum (measured by nitrate reductase reduction method); (4) variations of TNF-a and ICAM-1 amoung different groups (measured by immunohistochemical method and image analysis).4. Results:(1) DAI and pathologic changesAfter infection, DAI of the rats in the model group increase dramatically (P< 0.01). Both BQIRT prescription and mesalazine are found to be effective to reduce DAI in acute stage (P<0.05) and inactive stage (P< 0.01). Compared to mesalazine, the effect of BQIRT prescription in inactive stage is found to be much more significant, as the DAI of rats in BQIRT group are remarkably lower (P<0.05).With respect to symptoms, mucous membranes of the rats in the model group fall off, necrose, ulcerate and swelling due to widely inflammatory cell infiltration on the membranes. Mesalazine is found to be capable in repairing most of the inflammatory injuries in acute stage. However, the growth of granulation tissue in inactive stage is slow after the treatment of mesalazine. Correspondingly, BQIRT prescription is less effective in repairing the inflammatory injuries in acute stage, while the growth of granulation tissue in inactive stage is significantly faster. Thus, the rats in the BQIRT group have fewer ulcerations in inactive stage and recover faster.(2) Changes of ultra-structures on colonic mucosal epithelial cells and mitochondrial structuresUC significantly destructs the ultra-structures on colonic mucosal epithelial cells after infection, causing cellular swelling, damaging microvilli, reducing organelles and leading to swelling and damage of mitochondria and endoplasmic reticulum. These symptoms last over time but naturally relieve to a certain extent. Both mesalazine and BQIRT prescription can sufficiently relieve these symptoms in acute stage, while BQIRT tends to be more effective in the case of the recovering of ultra-structures. Subsequently, in inactive stage, ultra-structures of rats treated by BQIRT prescription almost recover completely while those in mesalazine group barely recover, which indicates that mesalazine is deficient in lasting effects in inactive stage compared to BQIRT prescription.The Flameng indexes of the rats in the model group gradually decline over time but always remarkably higher than those of the normal group (P<0.01). In acute stage, the indexes of both the BQIRT group and the mesalazine group are lower than those of the model group (P<0.01), higher than those of the normal group (P<0.01). In inactive stage, the indexes of the BQIRT group are lower than those of the mesalazine group and steadily decline, approaching those of the normal group (P<0.05). It is noteworthy that mesalazine hardly reduces the indexes in inactive stage.(3) Variations of NO concentrations in the serumSimilar to the Flameng index, NO concentrations in the serum (called NO here in after), NOs of the rats in the model group gradually decline over time but always remarkably higher than those of the normal group (P<0.01). In acute stage, NOs of both the BQIRT group and the mesalazine group are lower than those of the model group (P<0.01), higher than those of the normal group (P<0.01). In inactive stage, NOs of the mesalazine group decease. Simultaneously, NOs of the BQIRT group decease much more rapidly (P<0.01). As a result, NOs of the BQIRT group are lower than those of mesalazine group (P<0.05) and significantly lower than those of model group (P<0.05).(4) Variations of TNF-a and ICAM-1TNF-a levels of the rats in the model group gradually decline over time (P<0.05) but always remarkably higher than those of the normal group (P<0.01). In acute stage, both the BQIRT prescription and the mesalazine reduce the TNF-a levels (P<0.05) and the mesalazine is found to be more efficient (P<0.05). In inactive stage, the reduction TNF-a levels of the BQIRT group are more remarkable than those of the mesalazine group (P<0.05), approaching the levels of the mesalazine group.ICAM-1 levels of the rats in model group gradually decline over time (P<0.05) but always remarkably higher than those of normal group (P<0.01). BQIRT prescription and mesalazine reduce the TNF-a levels in both acute stage (P<0.05) and inactive stage (P<0.05). In inactive stage, the reduction TNF-a levels of the BQIRT group are faster than those of the mesalazine group (P<0.05).5.Conclusions:(1) Inflammatory reaction, immune injury and ultra-structures in membranes damage exist along with UC, being intense in acute stage and relieving in inactive stage, which could be the key pathomechanism of UC. (2) In acute stage, BQIRT prescription and mesalazine have similar curative effects, but mesalazine reducing immune injury more effectively by restraining inflammation. (3) In inactive stage, BQIRT prescription has better lasting curative effects as BQIRT is better at reducing inflammation and repairing immune and ultra-structures damage persistently. That is because spleen deficiency and sustaining toxin are the keys of pathomechanism of UC in inactive stage, and BQIRT aims at these essences other than symptoms. Therefore, BQIRT, which is capable of sufficiently repairing damage in colonic mucosa, improving immunity by correcting the immune disorder, increasing cure rate, decreasing recurrence rate, is an appropriate cure for UC.