| Background:Recurrent oral ulcer is also known as recurrent aphthous ulcer,which is characterized by pain,periodicity,self-limited and recurrence.The incidence rate of recurrent oral ulcer is very high and there are many kinds of therapeutic drugs,but it still can not be cured clinically.It is one of the refractory diseases of oral mucosa,and its occurrence and development are closely related to the disorder of immune system.Tregs and TH17 are two kinds of immune cells that have the same differentiation path and different functions.The imbalance of their differentiation ratio is an important factor in inducing the disorder of their own immune system.Activation of TGF-?1 and high expression of TEAD1 can mediate the HIPPO signaling pathway and promote CD4+T naive cells differentiate into Tregs.Professor wang hanming's research group found that yukouning decoction could promote ulcer healing in patients with recurrent oral ulcer(heart and spleen heat accumulation syndrome)and increase the content of CD4+T lymphocytes and TGF-?1 in the blood.Therefore,we suspect that Yukouning may promote the differentiation of CD4+CD25+Foxp3+Tregs by regulating the TGF-?/TEAD1/FOXP3 signaling pathway,further regulate the immune status of patients with RAU,and promote ulcer healing.Based on SD rats with RAU(syndrome of accumulation of heat in the heart and spleen),this report explored the deep mechanism of Yukouning in the treatment of RAU and provided theoretical basis for its promotion and application.Objective:To explore the mechanism of Yukouning-mediated TGF-?1/TEAD 1/FOXP3 signaling pathway regulating the differentiation of Tre gs in RAU(syndrome of accumulation of heat in the heart and sp leen).Methods:1?A total of 30 patients were randomly selected from January 2019 to December 2019 at the Department of Stomatology,Hubei Ma ternal and Child Health care hospital,who were clinically diagn osed with recurrent oral ulcer(syndrome of accumulation of heat in the heart and spleen),and were included in the experiment af ter signing the informed consent.The improvement of patient ' s u lcer number?area?feeling of pain and burning sensation?conge stion?ulcer duration?xerostomia?thirst?constipation and dar k yellow urine were observed before and after treatment.2?The immune method was used to induce the appearance of ulcer s.A total of 40 rats with heat accumulation syndrome of heart a nd spleen were created using mold irritations and a high-fat an d spicy diet.Pictures were taken after successful modeling.40 r ats were randomly divided into 4 groups and respectively gavage d with normal saline,levamisole,Qingrejiedu and Yuokuning decoc tion for 1 weeks.After 1 weeks,the rats were sacrificed,and the ulcerative mucosas were retained for HE staining.The abdominal aortic blood samples were collected and the contents of CD4+CD 25+Foxp3+Tregs in the blood of the rats were detected by flow c ytometry.3?SD rats were randomly divided into 4 groups after successful modeling of RAU(syndrome of accumulation of heat in the heart a nd spleen),and were respectively gavaged with normal saline,le vamisole,Qingrejiedu and Yuokuning decoction for 1 weeks.After 1 weeks,the rats were sacrificed,the ulcer tissues were strippe d,the tissue protein was extracted,and the expression levels of TGF-? 1,TEAD1 and TAZ were detected.Results:1?After 4 weeks of treatment,the effective rate of ulcer area reduction in patients with recurrent oral ulcers was 87%.The e ffective rate of ulcer pain reduction is 90%.The effective rat e of congestion reduction is 97%.The effective rate of reducin g burning sensation is 93%.The effective rate of reducing the number of ulcers is 87%,and the effective rate of shortening t he duration of ulcers is 100%.The relief of xerostomia and thi rst is 93%,the efficiency of constipation is 100%,and theeffi ciency of dark urine improvement is 100%.2?(1)After modeling by immune induction method,ulcers appeared in the lower right buccal side of SD rats' mouth.The base of th e ulcer was sunken and the surface of the ulcer was irregular a nd covered with a gray-white pseudomembrane.The surroundin muco sal tissue was slightly congested,and the amount of saliva in t he ratv s mouth was abundant.(2)After 1 weeks of gavaged with normal saline,HE tissue sectio ns showed epithelial defects?discontinuousness,and a large n umber of inflammatory cells infiltrated in the lamina propria w hile the levamisole group showed continuous epithelium with a s mall amount of inflammatory cells infiltration in the lamina pr opria.The epithelium of Qingrejiedu group and Yukouning group w ascomplete and continuous,and there was no obvious inflammator y cell infiltration in the lamina propria.(3)The level of CD4+CD25+Foxp3+Tregs cells in the levamisole gr oup and the saline group had no significant difference(P>0.05).The level of CD4+CD25+Foxp3+Tregs in the Qingrejiedu group and the Yukouning group was increased compared with the saline group.Among them,the content of CD4+CD25+Foxp3+Tregs in the Yuk ouning group was significantly higher than that in the normal s aline group(P<0.05),but the level of CD4+CD25+Foxp3+Tregs in t he Qingrejiedu demolition group was not significantly different from that in the normal saline group(P>0.05).3.Compared with the normal saline group,the level of TGF-?1 in the levamisole group,Qingrejiedu group and the Yukouning group increased significantly.Compared with the normal saline group,the level of TEAD1 in levamisole group decreased,while that of TEAD1 in Qingrejiedu and the Yukouning group increased.The level of TAZ in levamisole group,Qingrejiedu and Yukouning group decreased,among which,the level of TAZ in Qingrejiedu and Yukouning group was lower than that in levamisole group.Conclusion1?As a clinical prescription,Yukouning not only relieves the pain of oral ulcer,promotes ulcer healing,but also significant ly relieves constipation,dark yellow urine and other symptoms o f patients.It has obvious short-term curative effect and exerts the unique advantages of Chinese herbal medicine.2?(1)Yukouning,Qingrejiedu and levamisole groups can promote epithelial hyperplasia of oral ulcer,restore epithelial contin uity,and reduce inflammatory cell infiltration in lamina propri a.(2)Yukouning decoction can obviously promote the level of CD4+CD25+Foxp3+Tregs in RAU rat blood.3?Yukouning and Qingrejiedu groups can significantly promote t he expression of TGF-? 1,TEAD1 protein and inhibit the content of TAZ protein,suggesting that Yukouning and Qingrejiedu groups may activate HIPPO signaling pathway by regulating TGF-? 1.Yuk ouning's promotion of CD4+CD25+Foxp3+Tregs cell production mayb e caused by stimulation of the Hippo signaling pathway. |
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