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Fibrosis can occur in nearly all organs of the body and is an outcome of many chronic diseases. As inflammation leads to necrosis of parenchymal cells， excessive proliferation of fibroblasts and overproduction of extracellular matrix （ECM） occur in tissues and organs， which may cause structural damage and loss of function of organs in the case of continuous progression. Chinese medicine has definite effect on fibrosis and prescriptions with effects of replenishing Qi and activating blood， such as Buyang Huanwutang， are frequently used in clinical settings. Clinical research and experiments show that Buyang Huanwutang can delay the progression of fibrosis in multiple organs such as lung， heart， liver， and kidney by improving organ function， reducing ECM deposition， anti-oxidative stress， anti-inflammatory response， regulating the imbalance of matrix metalloproteinases （MMPs）/tissue inhibitors of metalloproteinases （TIMPs）， and modulating transforming growth factor-β （TGF-β）/Smad pathway. According to traditional Chinese medicine， healthy Qi deficiency is the internal cause of fibrosis， and blood stasis is an important pathological factor in the formation of fibrosis. Moreover， deficiency and stasis exist in the whole process of fibrosis and the changes of microenvironment of fibrotic organs and tissues accord with the pathological manifestations of Qi deficiency and blood stasis. This article reviews the anti-fibrosis mechanism of Buyang Huanwutang in multiple organs， which provides a science-based explanation for the treatment of fibrosis by Buyang Huanwutang and lays a foundation for further clinical research.
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Objective:To observe the effect of modified Si Junzitang on the level of lactic acid in gastric mucosa and the expression of Carboxylic acid transporter 1（MCT1）， monocarboxylic acid transporter 4（MCT4）， and extracellular matrix metalloproteinase inducer （CD147）in rats with gastric precancerous lesions（GPL）. Method:Seventy-four SD male rats were randomly divided into normal group （12 rats） and model group （62 rats）. <italic>N</italic>-methyl-<italic>N'</italic>-nitro-<italic>N</italic>-nitrosoguanidine（MNNG）-ammonia compound method was used to establish GPL rat models， and at the 9<sup>th</sup> week， the model rats were randomly divided into model group， folic acid group（2.7 mg·kg<sup>-1</sup>）， modified Si Junzitang high， medium and low dose groups（12.6， 6.3， 3.15 g·kg<sup>-1</sup>）， with 12 rats in each group. After intragastric administration for 12 weeks， the general conditions of the rats were observed. Hematoxylin-eosin（HE）staining was used to observe the histopathological changes of gastric mucosa in rats， chemical colorimetry was used to detect the content of lactic acid in gastric mucosa； immunohistochemistry and real-time polymerase chain reaction（Real-time PCR）were used to detect MCT1， MCT4， CD147 protein and mRNA expression in gastric mucosal tissues. Result:Modified Si Junzitang significantly improved the pathological manifestations in GPL rats such as gastric mucosal epithelial gland structure， disorder of arrangement and cell atypia. Compared with the normal group， the lactic acid content of the gastric mucosa tissue in the model group increased significantly（<italic>P</italic><0.01）， and the protein and mRNA expressions of MCT1， MCT4， CD147 significantly increased（<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the lactic acid content in each dose group of modified Si Junzitang was significantly reduced（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the protein expression levels of MCT4 and CD147 were also significantly reduced in each dose group of modified Si Junzitang（<italic>P</italic><0.05， <italic>P</italic><0.01）. The mRNA expression of MCT4 was significantly reduced in the middle and high dose groups（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the mRNA expression of CD147 was significantly reduced in the high dose group（<italic>P</italic><0.05）. Modified Si Junzitang showed no significant regulatory effect on MCT1. Conclusion:Modified Si Junzitang can significantly improve the abnormal histopathology of gastric mucosal epithelium in GPL model rats. Its mechanism may be related to down-regulating the overexpression of MCT4 and CD147， inhibiting lactic acid outflow， and improving the acidic microenvironment of gastric mucosal epithelium.
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Objectives:To investigate the therapeutic effect and mechanism of modified Fuzi Lizhongtang on ulcerative colitis （UC） model rats. Method:The 72 male SD rats were randomly divided into normal group，model group，sulfasalazine group（0.5 g·kg-1），modified Fuzi Lizhongtang high，medium and low-dose group （23.62，11.81，5.91 g·kg-1）. These rats were used to replicate the UC rat model by 2，4，6-trinitrobenzene sulfonic acid （TNBS）-ethanol composite modeling and treated by gavage for 2 weeks. The general condition of rats in each group was observed. After anesthesia，blood was collected from abdominal aorta and colonic tissue was taken. Semi quantitative evaluation by the colon mucosa damage index （CMDI），the pathological changes of colonic tissue were observed by the hematoxylin and eosin （HE） staining. The contents of serum interleukin-4 （IL-4），IL-6，IL-10 and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of mammalian target of rapamycin（mTOR） and phosphorylated ribosomal protein S6 kinase 1 （p-S6K1） in colonic mucosa were detected by immunohistochemistry （IHC） and Western blot. Result:Compared with normal group，the CMDI score of the model group rats was significantly increased （P<0.01）. The contents of IL-4 and IL-10 in serum were significantly decreased，the contents of IL-6 and TNF-α were significantly increased （P<0.01）. The expression levels of mTOR and p-S6K1 in colonic mucosa were up-regulated （P<0.01）. Compared with model group，the CMDI score of the modified Fuzi Lizhongtang high dose group was significantly decreased （P<0.05）. In modified Fuzi Lizhongtang high and medium dose group，the contents of IL-6 and TNF-α were significantly decreased （P<0.01） and the contents of IL-4 and IL-10 in serum were significantly increased （P<0.05，P<0.01）. In the modified Fuzi Lizhongtang high dose group，the expression level of mTOR and p-S6K1 protein was down-regulated significantly （P<0.05，P<0.01）. Conclusion:Modified Fuzi Lizhongtang high dose group can significantly reduce the congestion and edema，inflammatory cell infiltration，gland distortion，disorder of arrangement and other pathological manifestations of UC colon mucosa，and its mechanism may be related to its down-regulation of mTOR/p-S6K1 signal and the regulation of inflammatory factors secretion.
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Objective:Through the preparation of Alzheimer's disease （AD） rat model， the effect of Yuanzhisan on the expression of Ghrelin was observed， and the possible mechanisms in preventing and treating AD were discussed. Method:A total of 120 SD rats were randomly divided into sham-operated group， model group， donepezil group（1.02 mg·kg-1）， and high， medium and low-dose Yuanzhisan groups （12，6，3 g·kg-1）， with 20 rats in each group， including half male and half female. The rats in sham-operated group were injected with normal saline （NS）， and the rats in other groups were injected with β-amyloid 1-40 （Aβ1-40） in hippocampus to induce the AD rat model. During the 10-week continuous gavage， the food intake of rats in each group was observed and recorded. After the end of gavage， learning and memory abilities of rats were tested by Morris water maze. The whole brain and the gastric body and antrum were collected， the pathologic changes in the CA1 area of hippocampus was assessed by hematoxylin-eosin （HE） staining， and the expression of Ghrelin was detected by immunohistochemistry. Result:Compared with the sham-operated group， the escape latency time of model group rats increased （P<0.01），while times across platform， retention time in effective area and movement distance decreased （P<0.01）. The disorder of neurons， the decrease of the neuronal number， and the pyknosis of nucleus were observed in hippocampal CA1 area. The food intake of male and female rats decreased significantly （P<0.05，P<0.01）. The expression of Ghrelin in hippocampal CA1 area and gastric mucosa decreased significantly （P<0.01）. Compared with the model group， the escape latency time of rats in each treatment group was significantly shortened （P<0.05，P<0.01），whereas times across platform， retention time in effective area and movement distance increased （P<0.05，P<0.01）. The pathologic change was improved markedly， and the daily food intake of rats in high and medium-dose Yuanzhisan groups increased significantly （P<0.05，P<0.01）. The protein expression of Ghrelin in hippocampal CA1 area and gastric mucosa increased significantly in each Yuanzhisan group （P<0.05，P<0.01）. Conclusion:Yuanzhisan can effectively improve the learning and memory abilities of AD rats and increase the daily intake， which may be related to its up-regulation of Ghrelin content in hippocampal CA1 area and gastric mucosa.