| Reflux esophagitis(RE)is an inflammatory disease of the esophagus caused by the reflux of the contents of the stomach and duodenum into the esophagus,causing damage to the esophageal mucosa.It is widespread worldwide and has occurred in recent years.Gradually increasing,proton pump inhibitor(PPI)is the first choice for the treatment of RE.It has a faster onset but has more side effects and a higher recurrence rate after stopping the drug.Traditional Chinese medicine treatment of RE can show certain advantages in alleviating clinical symptoms and reducing recurrence rate,and has gradually become a research hotspot.This study is divided into three parts:The first part is a literature study,which mainly describes the research progress of RE in Chinese and Western medicine;the second part is a clinical efficacy study,which verifies the clinical efficacy of Jianpi Jiangni Recipe on Zhong-deficiency Qi Ni type RE.And through follow-up to evaluate the long-term efficacy;the third part is an experimental study,using cardia myotomy combined with pylorus half ligation to model RE rats,from regulating the cAMP/PKA signaling pathway and upstream and downstream related protein expression To explore the mechanism of Jianpi Jiangni Recipe in the treatment of RE.MethodsClinical study:131 cases of RE with middle-deficiency inverse type were included and randomly divided into 64 cases in the control group and 67 cases in the treatment group.The treatment group was given Jianpi Jiangni Granules orally twice a day,and the control group was given Omeprazole enteric-coated tablets orally,20 mg/time,twice/day.The medication period is 8 weeks.The two groups are tested for safety before and after treatment.MTL,VIP,and Ghrelin of the treatment group are compared before and after treatment,and questionnaires are carried out at 3 months,6 months,and 12 months after stopping the drug.Experimental study:8-week-old SD rats were selected and used cardia muscle incision combined with half ligation of the pylorus for RE modeling.After modeling,they were divided into 6 groups:sham operation group,model group,and control group,Chinese medicine high-dose group,Chinese medicine middle-dose group and Chinese medicine low-dose group,each group has 6 animals.Sham operation group and model group were given distilled water gavage,the control group was given omeprazole enteric-coated tablets by gavage,and the Chinese medicine group respectively Different concentrations of Jianpi Jiangni Recipe were administered by gavage,and the samples were taken 14 days after gavage.The serum VIP and Ghrelinl contents in rats were determined by ELISA method;VIP,VPAC2,Ghrelin,GHSR,cAMP and PKA mRNA in lower esophageal tissue were detected by PCR Expression;Western Blot method was used to detect the expression of cAMP and PKA in the lower esophagus,and the positive expression of ROCK1 and MLC was detected by immunohistochemistry.ResultsClinical research part:(1)For the GerdQ scale score,after taking the medicine for 8 weeks,both Jianpi Jiangni Recipe and Omeprazole can effectively reduce the total score.There is no significant difference between the two.The long-term effects of Nifang at 3 months and 6 months are better than omeprazole,and there is no significant difference between the withdrawal of the drug for 3 months and the withdrawal of the drug for 6 months.However,omeprazole has repeated symptoms after 3 months of discontinuation,and the degree is similar to that of 6 months of discontinuation and 12 months of discontinuation.(2)Judging the recurrence rate according to the GerdQ scale,Jianpi Jiangni Decoction is better than omeprazole in 3 months,6 months,and 12 months,which is consistent with the results of long-term efficacy comparison.(3)Regarding the main symptom scores in the TCM Symptom Grading Scale,Jianpi Jiangni Decoction is better than omeprazole after treatment,3 months withdrawal,6 months withdrawal,and 12 months withdrawal,And showed the same trend as the GerdQ scale in terms of long-term efficacy:Jianpi Jiangni Recipe did not show any significant difference between the withdrawal of the drug for 3 months and the withdrawal of the drug for 6 months,and it was only after the withdrawal of the drug for 12 months.There is a significant decrease in curative effect,which reflects a better maintenance effect on the curative effect.However,omeprazole has repeated symptoms after 3 months of discontinuation,and the degree is similar to that of 6 months of discontinuation and 12 months of discontinuation.(4)Regarding the secondary symptom scores in the TCM Symptom Grading Scale,the efficacy of Jianpi Jiangni Decoction is better than omeprazole after treatment,3 months withdrawal,6 months withdrawal,and 12 months withdrawal.(5)After treatment,the serum MTL content in the treatment group was higher than before treatment,the serum VIP content was lower than before treatment,and the expression of Ghrelin in the stomach fundus was higher than before treatment.Experimental research part:(1)After modeling,the rats in the sham operation group are better than the other 5 groups in terms of hair luster,movement,food and water consumption.On the 7th day after the operation,2 rats in the non-sham operation group were randomly selected,and the general and pathological morphology of the esophagus were observed after HE staining to verify the success of the model.(2)Compared with the control group and the low-dose group of traditional Chinese medicine,the high-dose and medium-dose Chinese medicine group can effectively reduce the expression of VIP and receptor VPAC2 mRNA;the high-and medium-dose Chinese medicine group is more effective than the control group and the low-dose Chinese medicine group.It can effectively increase the expression of Ghrelin and receptor GHSR mRNA.(3)Both the high and medium dose groups of traditional Chinese medicine can significantly reduce the expression levels of cAMP and PKA mRNA.(4)The high-dose group of traditional Chinese medicine can increase the expression of cAMP/PKA downstream proteins ROCK1 and MLC.ConclusionIn this study,it was verified that Jianpi Jiangni Decoction has a short-term effect(within 8 weeks)on the typical symptoms of RE and is equivalent to omeprazole.At the same time,it has a significant effect on relieving atypical symptoms and maintains the effect after stopping the drug.It has obvious advantages,which is compatible with the effects of Jianpi Jiangni Recipe to replenish qi and invigorate the spleen,reduce stomach qi,cure the root cause and protect the symptoms.After observing the clinical efficacy of Jianpi Jiangni Decoction on RE,animal experiments verified that Jianpi Jiangni Decoction can regulate the secretion of VIP and Ghrelin and reduce the damage of esophageal mucosa.Its mechanism of action may be related to down-regulating the activity of cAMP/PKA signaling pathway,increasing the expression of downstream proteins ROCK1 and MLC,enhancing smooth muscle contraction,and promoting gastric emptying. |
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