| ObjectiveThis study summarizes the origins,etiology,pathogenesis,and syndrome differentiation of gastric epilepsy,and finds that the treatment of gastric epilepsy is based on "intrinsic carbuncle",and that the combination of drugs and white can improve the efficacy.At the same time,through experimental research,based on the inflammatory injury and IL-6 mediated TLR4 signaling pathway key molecules to explore the traditional Chinese medicine white and the main component of white and polysaccharides on gastric ulcer rat gastric mucosa pathological damage improvement and molecular mechanism for clinical application Provide theoretical basis.MethodsLiterature Research: Using traditional philological research methods,using the keywords of "stomach pain","stomach pain","stomach ulcer" and "Baiji" as keywords,we collected and organized CNKI and China Biotechnology from January 1989 to December 2019 The full-text database of medicine（CBMdisc）on gastric epigastric（gastric ulcer）,white and related journal literature,summarizes and analyzes the origin of gastric epigastric disease,etiology and pathogenesis and treatment of different syndromes,the prescription of medicines,and the combination of the family from the " "Nai carbuncle" discusses the treatment of gastric pain（gastric ulcer）,compatibility with Bai and medication experience,and provides literature and practical basis for Bai and clinical application.Experimental Study: 72 SPF Wistar rats weighing（180±10）g were randomly divided into blank control group（n=10）,GU model group（n=62）.Except for the normal feeding of rats in the blank group without modeling,the other rats were reconstructed the GU model by the acetic acid cauterization.After the successful reconstruction of the model,a total of 50 GU rats were equally and randomly divided into five groups,10 rats in each group: model group,ranitidine hydrochloride group,BSP high-dose group(500 mg·kg-1,BSP-500),BSP middle-dose group(250 mg·kg-1,BSP-250),BSP low-dose group(125 mg·kg-1,BSP-125).The blank control group and the model group were fed with distilled water according to the volume of 10ml·kg-1·d-1.The ranitidine hydrochloride group was fed with 300 mg·kg-1 ranitidine hydrochloride daily.The high,middle and low dose groups of BSP were fed with 500 mg·kg-1,250 mg·kg-1,125 mg·kg-1 BSP respectively for 15 days.This study consists of three parts.The first chapter explores the effects of BSP on the general survival status,ulcer index,ulcer healing rate,pepsin activity,serum NO content,histopathological changes of gastric mucosa and pathological degree of gastric tissue in Gu rats.In the second chapter,the effect of BSP on the gene and protein expression of JNK,p38 MAPK,PI3 K,and AKT of the key pathways mediated by TLR4 and the expression levels of downstream cytokines IL-17 and IL-23 in the microenvironment of gastric mucosa of GU rats were studied.The content changes of IL-17 and IL-23 in serum and gastric mucosa of GU rats were detected by Elisa method and the gene expressions of IL-17 and IL-23 were detected by RT-PCR method.RT-PCR method and Western blot method were used to detect the gene and protein expression of JNK,p38 MAPK,PI3 K,and AKT in the gastric mucosa.The third chapter discusses the effect of BSP on the activation level of NF-κB p65 in the gastric mucosa of GU rats and the inflammatory cascade reaction mediated by NF-κB p65.The content changes of IL-1β,IL-6,TNF-α and IL-2R in serum and gastric mucosa were detected by Elisa method.RT-PCR method was used to detect the m RNA expression levels of NF-κB p65,IL-1β,IL-6,TNF-α and IL-2R.The expression level of NF-κB p65 in gastric mucosa of rats in each group was detected by Western blot.ResultsLiterature Research:Chinese herbal medicine Baiji has the functions of converging and stopping bleeding,reducing swelling and growing muscles,and Baiji has a long history of application and practical basis in the treatment of gastric ulcer.Experimental Study:In the first chapter,compared with the blank control group,GU rats showed the following symptoms: mental depression,serious bristle,bloody stools,significant increased ulcer area,content of serum NO and pepsin activity（P<0.01）.The histopathology of gastric mucosa showed that there were the disappearance of glands,the infiltration of inflammatory cells,the appearance of necrotic layer,the obvious granulation layer and scar tissue.Compared with the model group,the mental state of rats in each treatment group was gradually improved,the amount of diet was flat or increased,the blood stool was gradually disappeared.The ulcer index of rats in ranitidine hydrochloride group and BSP-500 group was significantly reduced,and the content of serum NO and activity of pepsin were significantly reduced when compared with those of the model group（P<0.01）.In the BSP-250 group and the BSP-125 group,although the ulcer area,serum NO content and pepsin activity of rats were decreased in different degrees,the difference was not statistically significant.In the second chapter,compared with the blank control group,the content and m RNA expression level of IL-17 and IL-23 in the serum and gastric mucosal were significantly increased,and the expression levels of m RNA and protein of TLR4,JNK,p38 MAPK,PI3 K,AKT in gastric mucosal were also significantly increased（P<0.01）.Compared with the model group,the content and the m RNA expression of IL-17 and IL-23 in the serum and gastric mucosa of rats in the ranitidine hydrochloride group and BSP-500 group were significantly reduced,and the expression levels of m RNA and protein of TLR4,JNK,p38 MAPK,PI3 K and AKT in the gastric mucosa were significantly decreased（P < 0.05 or P < 0.01）.Simultaneously,in the gastric mucosa of the BSP-250 group,the m RNA expression levels of IL-17,JNK,p38 MAPK,PI3 K,and AKT,and the protein expression levels of JNK and AKT were significantly reduced（P<0.05 or P<0.01）.The expression of the above factors in the BSP-125 group only showed a decreasing trend,but the difference was not statistically significant（P>0.05）.In the third chapter,compared with the blank control group,were significantly increased,and the expression levels of m RNA and protein of NF-κB p65 were also significantly increased（P<0.05 or P<0.01）.Compared with the model group,the content and m RNA expression level of IL-1β,IL-6,TNF-α,IL-2R and the expression levels of m RNA and protein of NF-κB p65 in the ranitidine hydrochloride group and BSP-500 group were significantly decreased（P<0.05 or P<0.01）.In the gastric mucosa of the BSP-250 group,the contents of IL-1β and TNF-α were significantly decreased,m RNA expression levels of TNF-α and IL-2R were significantly decreased,and the expression levels of m RNA and protein of NF-κB p65 were significantly decreased（P < 0.05 or P < 0.01）.Although the content and m RNA expression level of IL-1β,TNF-α and IL-2R in the serum and gastric mucosal of rats in the BSP-125 group were decreased in different degrees,the difference was not statistically significant（P>0.05）.Conclusions1.Literature research shows that the Chinese medicine Bai which has the functions of convergence and hemostasis,reducing swelling and growing muscle has a long-term application history and practical basis for the treatment of gastric ulcer.2.BSP can improve the general survival condition,reduce the ulcer index,improve the ulcer healing rate,reduce the pepsin activity and the content of serum NO,and improve the gastric mucosa injury in the course of GU.3.The expression levels of genes and proteins of TLR4,JAK,p38 MAPK,PI3 K,and AKT in gastric mucosa of GU rats are increased,which indicates that the formation of GU may be related to the high expression of m RNA and protein of key molecules of JNK/p38 MAPK signaling pathway and PI3K/AKT signaling pathway mediated by TLR4.BSP can promote the healing of GU by inhibiting the high expression of m RNA and protein of TLR4,JNK,p38 MAPK,PI3 K and AKT in gastric mucosa.4.The m RNA and protein expression levels of NF-κB p65 in the gastric mucosa of GU rats increased,and the contents and m RNA expression levels of IL-1β,TNF-α and IL-2R increased,which indicated that the chronic inflammatory pathological reaction of gastric mucosa in GU rats was related to the increased activation level of key molecules in the NF-κB p65 signaling pathway and the induction of downstream inflammatory cytokines that leads to the imbalance of pro-inflammatory and anti-inflammatory effects.BSP can promote the healing of GU by inhibiting the expression of NF-κB p65 and the secretion of proinflammatory factors in NF-κB p65 signaling pathway. |
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