ABSTRACT
ObjectiveTo observe the effect of Shenling Baizhusan on the intestinal inflammatory reaction in the rat model of Crohn's disease （CD） and study its relationship with p38 mitogen-activated protein kinase （MAPK） signaling pathway， so as to provide an experimental and theoretical basis for the clinical application of this prescription. MethodA total of 72 SD rats （36 males and 36 females） were randomized into a normal group （n=12） and a modeling group （n=60）. The rats in the modeling group were treated with 2，4，6-trinitrobenzene sulfonic acid （TNBS， 3 mL·kg-1） and then randomized into model， mesalazine （0.21 g·kg-1·d-1）， and low-， medium-， and high-dose （5.88， 11.76， 23.59 g·kg-1·d-1， respectively） Shenling Baizhusan groups. The rats in the drug intervention groups were administrated with corresponding agents by gavage for 14 days， and those in the normal and model groups with an equal volume of distilled water. The disease activity index （DAI） score of inflammatory bowel disease （IBD） and the colon mucosal damage index （CMDI） score of rats in each group were assessed after gavage. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the colon， and enzyme-linked immunosorbent assay （ELISA） to measure the levels of tumor necrosis factor alpha （TNF-α）， interleukin-1 （IL-1）， and interleukin-6 （IL-6） in the serum. Western blotting was employed to determine the protein levels of p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， p65 nuclear factor （NF）-κB， and phosphorylated-p65 NF-κB （p-NF-κB p65） in the colon tissue. Quantitative real-time polymerase chain reaction was conducted to determine the miRNA levels of p38 MAPK and NF-κB p65 in the colon tissue. ResultThe model group had higher DAI and CMDI scores than the normal group （P<0.01） and showed damaged epithelial cells in the colon mucosa， disarrangement of glands， damaged simple tubular glands， local necrosis， infiltration of a large number of inflammatory cells and lymphocytes in each layer， and presence of ulceration. Compared with the normal group， the model group showed elevated levels of TNF-α， IL-1， and IL-6 in the serum （P<0.01） and up-regulated protein levels of p-p38 MAPK and p-NF-κB p65 and miRNA level of p38 MAPK in the colon tissue （P<0.01）. Compared with the model group， mesalazine and high- and medium-dose Shenling Baizhusan decreased the DAI and CMDI scores （P<0.05， P<0.01）， repaired the mucosal epithelium of the colon tissue， increased the glands and goblet cells， lowered the levels of TNF-α， IL-1， and IL-6 in the serum （P<0.05， P<0.01）， and down-regulated the protein levels of p-p38 MAPK and p-NF-κB p65 and the miRNA level of p38 MAP in the colon mucosa （P<0.01， P<0.05）. ConclusionShenling Baizhusan can reduce intestinal inflammation of CD rats and promote the repair of colon mucosa by down-regulating the protein levels of p-p38 MAPK and pNF-κB p65 and the miRNA level of p38 MAPK to inhibit the p38 MAPK pathway.
ABSTRACT
The most common manifestations of inflammatory bowel disease （IBD） are Crohn's disease and ulcerative colitis， and the global incidence of IBD is on the rise. Traditional Chinese medicine （TCM） is advantageous in the treatment of IBD. IBD， with TCM names based on clinical symptoms， mostly belongs to recurrent dysentery， long dysentery， diarrhea， dysentery， bowel， and other categories. In TCM pathogenesis of IBD， spleen deficiency and exuberant dampness predominate in the whole course of the disease. Since the lung is associated with the large intestine and the lung Qi and spleen Qi are interconnected， the lung Qi and spleen Qi are deficient and the dampness and heat accumulate internally， which caused collateral obstruction by stagnant blood and the development of IBD. From the perspective of "associating lung with large intestine"，it is believed that the main mechanism of IBD is the Qi imbalance and abnormal metabolism of fluids in the lung and the intestine，and the nutrient-Yin injury of the lung and the intestine. According to the chronic， recurrent， and diffuse pathogenesis characteristics and main clinical manifestations of IBD， IBD is closely related to the lung and the intestine. In terms of therapeutic principles， IBD can be treated by tonifying the spleen and replenishing the lung， which highlights the treatment of the intestine from the lung. To be specific， in time of tonifying the spleen and removing dampness， the intestine is regulated by tonifying the spleen and replenishing the lung. Shenling Baizhusan， a commonly used classical prescription for IBD， is mainly potent in replenishing Qi， invigorating the spleen， draining dampness， checking diarrhea， and especially "reinforcing earth to generate metal". It can enhance the function of the lung through "reinforcing earth to generate metal"， which in turn regulates the intestine and promote the improvement of IBD. The present study clarified the mechanism of Shenling Baizhusan in regulating the intestine by tonifying the spleen and replenishing the lung. On the basis of modern research， its therapeutic effect on IBD was achieved through multiple links， such as regulation of the level of inflammatory factors， immunoregulation， barrier function improvement via mucosal repair， and intestinal flora. The findings of this study are expected to provide new ideas for the regulation of the lung-spleen-large intestine axis in the syndrome differentiation and treatment of IBD and subsequent experimental research.
ABSTRACT
Ulcerative colitis （UC） is one of the main manifestations of inflammatory bowel disease. Because of its lingering and refractory nature， it has become a major public health challenge worldwide. In the treatment of UC， traditional Chinese medicine （TCM） effectively relieves clinical syndromes， shortens the treatment period， reduces the frequency of recurrence， improves the quality of life， and reduces the occurrence of complications. To study the specific mechanism of TCM in the treatment of UC and screen out suitable drugs under the guidance of syndrome differentiation， the suitable UC animal model in the combination of disease and syndrome is used as an important method. This paper summarized and compared the UC animal model in the combination of disease and syndrome from five aspects， including selection of model animal species， sexual selection， preparation methods of UC animal model in the combination of disease and syndrome， indicators of model evaluation， and the main mechanism of TCM intervention in UC animal model in the combination of disease and syndrome. This paper aimed to provide references for the establishment of the optimal UC animal model in the combination of disease and syndrome. Research shows that UC syndrome mainly studied at present includes damp-heat syndrome， spleen deficiency syndrome， spleen-kidney Yang deficiency syndrome， spleen deficiency and dampness accumulation syndrome， liver depression and spleen deficiency syndrome， and cold-heat mixed syndrome.In the modeling method， the etiology simulation method is mainly used to first copy the syndrome type before the chemical agents or immune preparations were used to induce the disease model，and rats were often selected as the research objects，and the replication cycle was 7 to 28 days.The selected chemical reagents were mainly 5% dextran sulfate sodium（DSS） free drink, 2,4,6-trinitrobenzenesulfonic acid（TNBS） 100 mg·kg-1 and 50% ethanol 0.25 mL mixed reagent enema.This model replication method can take into account both UC pathogenesis characteristics of pathology of western medicine and TCM， syndrome type of traditional Chinese medicine and western medicine for interpretation pathological changes and TCM treatment of UC associated mechanism is of great significance， and help to help toestablish the optimal condition in combination with UC animal models for reference， for further research on prevention and treatment of UC specific mechanism of action of TCM model basis.