| Objective:1.After surgical resection,adjuvant chemothera y for 3-6 months is needed to reduce the recurrence and metastasis rate in treatment of colorectal cancer.For patients undergoing fluorouracil or capecitabine chemotherapy,gastrointestinal side effects are common adverse reactions,which may cause nausea,vomiting,diarrhea,or constipation.In China,many patients choose traditional Chinese medicine to reduce gastrointestinal side effects during chemotherapy.The overall efficacy of traditional Chinese medicine on gastrointestinal side effects during adjuvant chemotherapy for colorectal cancer needs to be evaluated through systematic study of the literature.2.Liujunanwei recipe is Professor Yang Yufei's experience prescription.It can significantly reduce the nausea,vomiting,diarrhea and other symptoms caused by chemotherapy by strengthening the spleen and stomach.The occurrence of gastrointestinal side effects is closely related to the damage of gastrointestinal mucosa.Whether Liujunanwei recipe has protective effect on chemotherapy-induced intestinal mucosal damage and the underlying mechanism need to be further clarified.Method:1.As of December 2020,we searched 8 databases and 2 clinical trial registration systems to collect the literature on the use of traditional Chinese medicine in the treatment of colorectal cancer during postoperative chemotherapy.According to the inclusion and exclusion criteria,literature selection,quality evaluation and data extraction were carried out.Whether to use other drugs as to reduce gastrointestinal side effects was used as the sub-group basis.Meta analysis was conducted to draw more objective and comprehensive conclusions in order to evaluate the effect of traditional Chinese medicine on KPS score,TCM syndrome score,gastrointestinal reaction,nausea and vomiting,diarrhea,constipation.2.To observe the protective effect of Liujunanwei recipe on intestinal mucosa of fluorouracil chemotherapy mice.Mice were intraperitoneally injected with fluorouracil 50 mg/kg for 7 days to establish the model of chemotherapy intestinal mucosal injury.From one week before the injection of fluorouracil,high,medium and low doses(15.66 g/kg,7.83 g/kg and 3.92 g/kg,respectively)of Liujunanwei recipe were given by gavage for 14 days.The weight and diarrhea of mice were observed during the intervention.On the 15th day,after sacrificed,measure the small intestine length.The effects of Liujunanwei Recipe on jejunal mucosa HE staining,intestinal stem cell proliferation,Wnt/?-Catenin pathway protein expression,intestinal permeability,gut microbiota changes and tight junction ZO-1,occludin,claudin-1 mRNA and protein were observed to verify the curative effect of Liujunanwei recipe and clarify its mechanism.Result:1.The results of meta-analysis showed that the collaborative use of traditional Chinese medicine during postoperative chemotherapy for colorectal cancer significantly reduced gastrointestinal symptoms such as nausea,vomiting,diarrhea and constipation,and avoided the decrease of KPS score and the increase of TCM syndrome score.During chemotherapy,even if the use of antiemetic and other symptomatic treatment,combined with traditional Chinese medicine treatment can still significantly reduce nausea and vomiting,diarrhea,improve KPS score,reduce TCM syndrome score.2.Fluorouracil chemotherapy significantly reduced the weight of mice in the model group,appeared obvious diarrhea and shortened the length of small intestine.HE staining of jejunal mucosa showed degeneration,necrosis and abscission of epithelial cells,shortening of villi and shallow destruction of crypt structure.The treatment of Liujunanwei recipe can significantly improve the weight of mice,the recovery of small intestine length,high villus height and deep crypt,and the high dose of Liujunanwei recipe has the best effect.3.Compared with the model group,Lgr5 +and BrdU + cells increased in the high-dose Liujunanwei.group.The results of immunohistochemistry and Western blot showed that the expression of Wnt and ?-Catenin protein in small intestine increased,and the expression of cyclin-D1 protein increased.4.The diversity of intestinal flora in the model group decreased compared with that before chemotherapy(Simpson index increased,P<0.05),the colony structure changed(PCA analysis before and after chemotherapy,P<0.05),the abundance ratio of mycobacteriaceae,enterococcaceae and bacteroideae decreased,and the abundance of veronicaceae and lactobacilliaceae increased.There was no significant difference in the diversity of intestinal flora in liujunan high-dose group after chemotherapy,which was close to the level before chemotherapy(PCA analysis before and after chemotherapy,P>0.05).The abundance of ackermanide and bifidobacteriaceae in intestinal flora was increased(P<0.05),which had a certain regulatory effect on the intestinal flora of fluorouracil chemotherapy mice.5.In the model group,the intestinal permeability was increased,and the expression of ZO-1,occludin and claudin-1 mRNA and protein were significantly decreased(P<0.05).Compared with the model group,the expressions of ZO-1,occludin and claudin-1 mRNA and protein in the high-dose liujunanwei group were increased.6.85%of the bacteria in the intestinal tract of mice were removed by the combined intervention of a variety of antibiotics to simulate a sterile environment.Under the simulated aseptic condition,the effects of different dose groups of Liujun Anwei Decoction on body weight,diarrhea,intestinal length,empty mucosal villus height and crypt depth of fluorouracil chemotherapy mice were not obvious.Conclusion:1.During the adjuvant chemotherapy of colorectal cancer surgery,the collaborative treatment of traditional Chinese medicine can reduce gastrointestinal symptoms such as nausea and vomiting,diarrhea,constipation,and avoid the decline of physical function and health status caused by chemotherapy,and improve the quality of life.2.Liujunanwei recipe has protective effect on intestinal mucosa,which can significantly reduce the damage of intestinal mucosa caused by chemotherapy,and may play its curative effect through gut microbiota.3.Liujunanwei recipe can increase the proliferation of intestinal stem cells and promote the repair of damaged mucosa by up regulating Wnt/?-Catenin pathway;at the same time,it can regulate gut microbiota,increase tight junction protein,reduce intestinal permeability and improve intestinal barrier. |
PDF Full Text Request