RESUMO
ObjectiveTo study the possible mechanism of Chaihu Shugan Powder （柴胡疏肝散， CSP） in the treatment of functional dyspepsia （FD）. MethodsTwenty-four SD rats were randomly divided into a normal group， a model group， a CSP group and a probiotic group， with six rats in each group.The tail-clamping provocation method was used in all groups except for the normal group to replicate the FD rat model. Simultaneously， the normal group and the model group were given 10 ml/（kg·d） of saline by gavage， while the CSP group and the probiotic group were given 9.6 g/（kg·d） of CSP aqueous decoction and 0.945 g/（kg·d） of probiotic aqueous solution by gavage， respectively， twice daily for four weeks. After four weeks， the gastric emptying and small intestinal propulsion rates were detected in each group of rats. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the gastric sinusoids and duodenum of the rats. The changes in the intestinal flora were analyzed by 16s rDNA high-throughput gene sequencing， and the expressions of the duodenal zona occludin 1 （ZO-1） and Occludin were detected by immunohistochemistry and western blotting. Pearson correlation analysis was performed on intestinal flora and ZO-1 and Occludin protein expression. ResultsThe gastric antrum tissue structure was clear in all groups， and the gland structure was regular， with smooth gastric tissue mucosa and no pathological changes such as erosion and ulcer. Compared to those in the normal group， the intestinal villi in the duodenal tissue in the model group were significantly reduced or atrophied， and the goblet cells were arranged in disorder， with eosinophilic infiltration； the gastric emptying rate and small intestinal propulsion rate， as well as ZO-1 and Occludin protein expression in duodenal tissue significantly decreased （P＜0.01）. Compared to those in the model group， the duodenal tissue structure was clear， and the length intestinal villi was longer， with goblet cells neatly arranged in the CSP group and the probiotic group； no obvious eosinophil infiltration was found， and the gastric emptying rate and small intestinal propulsion rate as well as ZO-1 and Occludin protein expression significantly increased in the CSP group； a small amount of eosinophil infiltration was found， and the gastric emptying rate and Occludin protein expression significantly increased in the probiotic group （P＜0.05 or P＜0.01）. Beta diversity analysis of intestinal flora showed that the overall structure of intestinal flora in the model group changed significantly compared to that in the normal group （P＜0.01）. The overall structure of the intestinal flora in the CSP group and the probiotic group was closer to the normal group than the model group. Species composition analysis showed that the relative abundance of the Firmicutes decreased， while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae increased， and the Bacteroidetes/Firmicutes value increased in the model group than those in the normal group （P＜0.05 or P＜0.01）. Compared to those in the model group， the relative abundance of the Firmicutes increased， while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae， as well as the Bacteroidetes/Firmicutes value decreased in the CSP group and the probiotic group （P＜0.05 or P＜0.01）. There was no statistically significant difference in each indicator between the probiotic group and the CSP group （P＞0.05）. Pearson correlation analysis showed that at the phylum level， Firmicutes was positively correlated with ZO-1 （r=0.610， P=0.016） and Occludin （r=0.694， P=0.004） protein expression. Bacteroidetes was negatively correlated with ZO-1 （r=-0.557， P=0.031） and Occludin （r=-0.662， P=0.007） protein expression. At the genus level， norank_f_Muribaculaceae was negatively correlated with ZO-1 （r=-0.727， P=0.002） and Occludin （r=-0.760，P=0.001） protein expression. ConclusionCSP can restore the structure of intestinal flora， regulate the abundance levels of Firmicutes， Bacteroidetes and norank_f_Muribaculaceae， up-regulate ZO-1 and Occludin proteins， and thus repairing the duodenal mucosal barrier， and playing a therapeutic role in FD rats.
RESUMO
OBJECTIVE： To analyze the formulation regularity of Chinese patent medicines containing Paeonia lactiflora， and to provide evidence for modern clinical application and R&D of P. lactiflora. METHODS： The formulations of Chinese patent medicine containing P. lactiflora were collected from Chinese Materia Medica Preparation and 2015 edition of Chinese Pharmacopeia. Statistical analysis was performed on the frequency of medicinal material， channel tropism， distribution of attending syndromes and attending diseases， core medicine combination （support degrees were set as 10％， 20％， 30％ and confidence degree was 0.9） by using data mining methods such as descriptive statistics and association rule analysis in TCM Inheritance System V 2.5； the formulation regularity of common attending syndromes and attending diseases （support degrees were set as 20％， 30％， 40％ and confidence degree was 0.9） was analyzed. RESULTS： A total of 600 Chinese patent medicine formulations contained P. lactiflora， involving 673 ingredients. The main medicinal properties in Chinese patent medicines containing P. lactiflora were warm， followed by cold and neutral. The main medicinal flavor was sweet， followed by bitter and pungent. The main channel tropism was spleen， liver and heart channel. There were 165 kinds of main treatment diseases （menstrual disorder， dysmenorrhea， dizziness） and 159 main treatment syndromes （insufficiency of qi and blood， qi stagnation and blood stasis， liver and kidney deficiency）. Under the condition of 30％ support degree and 0.9 confidence degree， there were 20 core combination of Chinese patent medicine formulations containing P. lactiflora （Glycyrrhiza uralensis-P. lactiflora， Angelica sinensis-P. lactiflora， P. lactiflora-Poria cocos） and 19 association rules among drugs. Under the condition of 40％ support degree and 0.9 confidence degree， there were 8 core medicines in Chinese patent medicines containing P. lactiflora for menstrual disorders （such as P. lactiflora， Cyperus rotundus， A. sinensis）， 9 core medicines for dizziness （such as P. lactiflora， Rehmannia glutinosa， A. sinensis）， 9 core medicines for qi and blood deficiency （such as P. lactiflora， Atractylodes macrocephala， P. cocos）， and 10 core medicines for qi stagnation and blood stasis syndrome （such as P. lactiflora， Aucklandia lappa， G. uralensis）. CONCLUSIONS： In this study， data mining was used to analysis the main symptoms， compatibility characteristics and formulation rules of Chinese patent medicines containing P. lactiflora， which can provide a basis for the modern clinical application and new drug development of P. lactiflora.