| Part I Literature Study on Traditional Chinese Medicine (TCM)Syndrome Types and Syndrome Element Distribution of Chemotherapy Gastrointestinal MucositisObjective: Based on the periodical data platform,we explored and analyzed the Traditional Chinese Medicine(TCM)Syndrome Types and syndrome element distribution of chemotherapy gastrointestinal mucositis.Methods:Taking“chemotherapy gastrointestinal mucositis”,“gastrointestinal reaction after chemotherapy”,“traditional Chinese medicine”,“syndrome differentiation” and “symptoms” as the theme words.All the literatures on the clinical research of Traditional Chinese Medicine(TCM)syndrome of chemotherapy gastrointestinal mucositis published in the full-text database of Chinese academic journals from 2010 to 2020 were searched.The frequency and frequency statistics,factor and cluster analysis were carried out on the retrieved data of Traditional Chinese Medicine(TCM)Syndrome Types and syndrome elements.Results: 197 literatures were selected,involving 15012 patients with chemotherapy cancer.There are 12 TCM syndrome types,which are spleen and stomach weakness syndrome(24.03%)> Chills and Fever Interties(18.01%)> qi stagnation and dampness obstruction syndrome(12.90%)> phlegm dampness syndrome(9.19%)> cold and dampness syndrome of spleen(8.34%)etc,and there are three types of cluster analysis.The results of syndrome elements showed that the disease location was mainly spleen and stomach.A total of 11 disease syndrome elements were extracted,which were Qi deficiency(28.41%)> internal cold(13.92%)> Qi Stagnation(12.06%)> fluid retention(10.15%)> internal heat(6.97%)> phlegm obstruction(turbidity)(5.34%)etc,and there were three types of cluster analysis.Conclusion: According to the syndrome types and the distribution characteristics of syndrome elements,the pathogenesis of chemotherapy gastrointestinal mucositis was often mixed with deficiency and excess,based on Qi deficiency,and marked by internal cold,qi stagnation,water dampness and phlegm,and internal heat.In the distribution of syndrome types,the weakness of spleen and stomach and the combination of cold and heat were the most important syndrome types.Among the disease syndrome elements,Qi deficiency was the key,and evil Qi such as internal cold,internal heat,phlegm turbidity and fluid retention were accompanied.This provided syndrome support for Shengjiang Xiexin Decoction in the treatment of chemotherapy gastrointestinal mucositis(chills and fever interties).Part II Clinical Observation of Shengjiang Xiexin Decoction in the Treatment of Chemotherapy Gastrointestinal Mucositis(Chills and Fever Interties)Objective: To evaluate the clinical effect of Shengjiang Xiexin Decoction in the treatment of chemotherapy gastrointestinal mucositis(Chills and Fever Interties),we adopted the clinical observation of Shengjiang Xiexin Decoction in the treatment of chemotherapy gastrointestinal mucositis.Methods: Using the method of case retrospective study,the cases of chemotherapy gastrointestinal mucositis with Chills and Fever Interties in the inpatient department of Oncology Department of Sichuan Hospital of traditional Chinese Medicine from June 2020 to March 2021 were collected.The epidemiological method was used to design the clinical observation flow chart of Shengjiang Xiexin Decoction in the treatment of chemotherapy gastrointestinal mucositis and the gastrointestinal quality of life index(GIQLI)after chemotherapy/traditional Chinese medicine treatment,and the patients were interviewed carefully.The general situation,symptom score,GIQLI and medication law of patients were statistically analyzed.Results: A total of 60 cases of gastrointestinal mucositis treated with Shengjiang Xiexin Decoction were collected.(1)Compared with the Traditional Chinese Medicine(TCM)main symptom score after chemotherapy,the clinical main symptom score after TCM treatment was significantly lower(P<0.01).(2)The distribution of tongue and pulse was mainly white tongue,white fur and thin pulse after chemotherapy;After TCM treatment,the tongue was light red,the coating was white and the pulse was fine.(3)Compared with the leukocytes of patients after chemotherapy,the leukocytes of patients after TCM treatment increased significantly(P<0.01).(4)Compared with the five dimensions and total score of GIQLI scale of patients after chemotherapy,the five dimensions and total score of patients after TCM treatment were significantly higher(P<0.01).(5)According to the characteristics of shengjiang Xiexin Decoction,Atractylodes macrocephala and poria cocos in benefiting Qi medicine,tangerine peel,perilla leaf and Amomum villosum in regulating Qi medicine,Huoxiang and Atractylodes macrocephala in resolving dampness medicine were used more frequently in the treatment of chemotherapy gastrointestinal mucositis.Conclusion: Shengjiang Xiexin Decoction could improve the clinical symptoms such as vomiting and diarrhea and improve the quality of life of patients after chemotherapy by reducing the TCM symptom score and increasing the five dimensions and total score of GIQLI.Chemotherapy gastrointestinal mucosal inflammation pathogenesis was deficiency mixed evidence,as well as Chills and Fever Interties.Shengjiang Xiexin Decoction plus and minus drugs were mainly Qi benefiting medicine,Qi regulating medicine and dampness resolving medicine.This provided clinical treatment support for the study of the relevant mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy gastrointestinal mucositis rats.Part III Experimental Study of Shengjiang Xiexin Decoction in the Treatment of Chemotherapy Gastrointestinal MucositisObjective: To evaluate the effect of Shengjiang Xiexin Decoction on chemotherapy gastrointestinal mucositis rats from the overall level and protein gene level.To explain the relevant mechanism of Shengjiang Xiexin Decoction in the prevention and treatment of chemotherapy gastrointestinal mucositis from the perspective of gastrointestinal inflammatory response and changes of aquaporin.Methods: Experiment 1: The rat model of chemotherapy gastrointestinal mucositis was established by single / multiple intraperitoneal injection of 5-FU.Eighteen Wistar rats were randomly divided into normal group,single injection of 5-FU group(ip,5-FU 277.77 mg · kg-1),multiple injection of 5-FU group(ip,5-FU 34.72 mg · kg-1 for 5 days),and intraperitoneal injection of equal volume normal saline in the normal group.we observed the weight,diarrhea and other general conditions of rats,and took blood from abdominal aorta to measure the indexes of leukocytes and platelets,and Serum IL-1β was detected by ELISA,so as to determine the best molding conditions.Experiment 2: according to the best modeling method in Experiment 1,72 Wistar rats were randomly divided into normal group(i.g,equal volume normal saline),5-FU model group(i.g,equal volume normal saline),low dose group of shengjiang Xiexin Decoction(i.g,3.5 g · kg-1 · d-1),medium dose group of shengjiang Xiexin Decoction(i.g,7 g · kg-1 · d-1),high dose group of shengjiang Xiexin Decoction(i.g,14 g · kg-1 · d-1),Sulfasalazine enteric coated tablets positive group(i.g,0.21 g · kg-1 · d-1).The normal group was injected intraperitoneally with equal volume of normal saline on the second day,and the other groups were made with ip,5-FU 277.77 mg · kg-1 on the second day.Then we observed and recordde the weight,diarrhea and other general conditions of rats,and took blood from abdominal aorta to measure blood routine indexes such as leukocytes and platelets.HE staining was used to observe the changes of gastrointestinal mucosa in rats.Serum was detected by ELISA,including TNF–α,IL-1β,PAF,IL-6,IL-10.Gastrointestinal tissue was detected by ELISA,including NF-κB,AQP2,AQP3,AQP4.Gastrointestinal tissue was detected by immunohistochemistry / Western blot,including NF-κB,AQP4 protein expression.Gastrointestinal tissue was detected by RT-PCR,including NF-κB and AQP4 m RNA expression.Result: Experiment 1:(1)Single injection of 5-FU caused diarrhea in rats,which decreased leukocytes and increased serum IL-1 β There was significant difference compared with multiple injections(P<0.01).(2)In the pathological changes of gastrointestinal HE staining,the damage of gastrointestinal mucosa could occur in the model rats.Compared with the multiple injection group,the damage of gastrointestinal mucosa in the single injection group was more serious.(3)From the aspects of clinical symptoms,inflammatory indexes and histological changes,it showed that a single injection of 5-FU is more in line with the acute injury of gastrointestinal mucosa caused by chemotherapy than multiple injections of 5-FU.Therefore,a single injection of 5-FU was selected as the best modeling condition for chemotherapy-induced gastrointestinal mucositis in rats.Experiment 2:(1)Compared with the model group,the low,medium,high dose groups and positive groups of Shengjiang Xiexin Decoction improved the diarrhea and weight loss of rats in varying degrees,and the effect of low dose group and positive group was the most significant(P<0.01).(2)The results of blood routine examination showed that compared with the normal group,the levels of leukocytes and platelets in each model group were significantly lower(P < 0.01 or P < 0.05),while the levels of red blood cells and hemoglobin had no significant changes among the groups.(3)The results of gastrointestinal HE staining showed that compared with the normal group,the gastrointestinal mucosa of model rats was damaged to varying degrees.Among them,the gastrointestinal mucosa of model rats was the most damaged,and the pathological manifestations such as gastrointestinal mucosa damage could be significantly inhibited in the positive group and low-dose group.(4)The results of ELISA showed that Shengjiang Xiexin Decoction could reduce the level of serum TNF-α,PAF,IL-1β,IL-6 in rats with chemotherapy gastrointestinal mucositis,and could increase the level of anti-inflammatory factor IL-10,and could reduce in rat gastrointestinal tissue NF-κB.The curative effect of low-dose and positive groups of Shengjiang Xiexin Decoction was significantly better than that of medium and high-dose groups(P < 0.01).At the same time,Shengjiang Xiexin Decoction could increase the levels of AQP2,AQP3 and AQP4 in gastrointestinal tissue of rats with chemotherapy gastrointestinal mucositis to varying degrees,so as to reduce the imbalance of water metabolism of gastrointestinal mucosa after chemotherapy.Among them,the low-dose group of Shengjiang Xiexin Decoction The curative effect of the positive group was significantly better than that of the medium and high dose groups(P < 0.01),but there was no significant difference between the low dose group and the positive group(P > 0.05).(5)The results of immunohistochemistry showed that Shengjiang Xiexin Decoction could reduce NF-κB expression of protein in gastrointestinal tissue of rats with chemotherapy gastrointestinal mucositis,and increase the expression of AQP4 protein in gastrointestinal tissue of rats with chemotherapy gastrointestinal mucositis.The curative effect of low-dose Shengjiang Xiexin Decoction group was significantly better than that of medium-dose group,high-dose group and positive group(P < 0.01).(6)Western blot and RT-PCR analysis showed that Shengjiang Xiexin Decoction could reduce NF-κB The expression of B protein and m RNA in gastrointestinal tissue of rats with chemotherapy gastrointestinal mucositis,so as to reduce the inflammatory reaction of gastrointestinal mucosa.At the same time,it could increase the expression of AQP4 protein and m RNA in gastrointestinal tissue of chemotherapy gastrointestinal mucositis rats to varying degrees,so as to regulate gastrointestinal water metabolism.The curative effect of Shengjiang Xiexin Decoction low-dose group was significantly better than that of medium dose group and high-dose group(P < 0.01),while the low-dose group was slightly better than that of positive group.Conclusion: Shengjiang Xiexin Decoction could reduce diarrhea,increase body weight,improve gastrointestinal mucosal damage in chemotherapy rats,and has the effect of preventing and treating chemotherapy gastrointestinal mucositis.The mechanism of Shengjiang Xiexin Decoction in preventing and treating gastrointestinal mucositis in chemotherapy rats may be through inhibiting NF-κB in gastrointestinal tissue activates,reducing the expression of inflammatory factor TNF-α,IL-1 β,IL-6 and promoting the expression of anti-inflammatory factor IL-10,and then affects the expression of AQP2,AQP3 and AQP4,so as to improve the inflammatory response and water metabolism disorder of gastrointestinal mucosa after chemotherapy.At the same time,we speculated that the anti-inflammatory mechanism of Shengjiang Xiexin Decoction in the prevention and treatment of chemotherapy gastrointestinal mucositis may be related to the expression of AQPs in gastrointestinal mucosa. |
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