| 1 ObjectiveStress ulcer is one of the main causes of prolonged hospital stay,poor prognosis and increased mortality in critically ill patients.In this study,we determined whether electroacupuncture can alleviate stress ulcer and improve prognosis in patients with severe neurological disease through clinical research.Furthermore,through basic research,we made it clear whether electroacupuncture can promote stress ulcer repair in mice under cold confinement,and whether the regulation of hypoxia-inducible factor-1α mediated by vagus nerve was the key mechanism of electroacupuncture effect.This subject will help to promote the application of electroacupuncture in the clinical treatment of stress ulcer and to provide scientific basis for further optimization of acupuncture and acupoint therapy.2 Methods2.1 Clinical researchTaking stress ulcer patients in adult neurocritical care as the research object,they were randomly divided into two groups,namely the therapy group(Electroacupuncture,EA group)and the control group(C group).Through the perioperative electro acupuncture intervention treatment,the main observation indicators of the two groups of patients were observed(the total effective rate of stress ulcers),secondary observation indicators(gastric juice pH,gastric juice occult blood test,stool occult blood test),related mechanisms(repair factors TFF2,VEGF,HSP70,heart rate variability),complications during hospitalization,and ICU stay Time and so on.2.2 Basic experiment1)Male C57BL/6 mice were randomly divided into Sham group,CRS group(stress ulcer modeling),CRS+EA group(stress ulcer modeling+electroacupuncture intervention).After modeling for 3 days and electroacupuncture treatment for 2 days,the mice in each group were subjected to gastric mucosal morphology observation(UI score)on the 6th day,and gastric tissues were collected.The mRNA expression level of repair factors(TFF2,VEGF,HSP70)were determined by RT-PCR,and the protein content and mRNA expression level of HIF-1α were determined by Western blot and RT-PCR.2)Male C57BL/6 mice were randomly divided into CRS+Vehicle group(solvent),CRS+PX478 group(inhibitor),CRS+Vehicle+EA group(solvent+electroacupuncture treatment),CRS+PX478+EA group(inhibitor)+Electroacupuncture treatment).After modeling for 3 days and electroacupuncture treatment for 2 days,the mice in each group were subjected to gastric mucosal morphology observation(UI score)on the 6th day,and gastric tissues were collected.The mRNA expression level of repair factors(TFF2,VEGF,HSP70)were determined by RT-PCR,and the protein content and mRNA expression level of HIF-1α were determined by Western blot and RT-PCR techniques.3)Male C57BL/6 mice were randomly divided into groups with CRS+Sham(sham operation),CRS+CVG(Cervical vagotomy),CRS+Sham+EA(sham operation+electroacupuncture),CRS+CVG+EA group(Cervical vagotomy+Electroacupuncture).After modeling and before electro acupuncture treatment,unilateral vagotomy was performed on the mice in the CVG group,and the vagus nerve was exposed but not cut in the mice in the Sham group.The mice in each group were subjected to gastric mucosal morphology observation(UI score)on the 6th day,and gastric tissues were collected.The mRNA expression level of repair factors(TFF2,VEGF,HSP70)were determined by RT-PCR,and the protein content and mRNA expression level of HIF-1α were determined by Western blot and RT-PCR techniques.3 Research result3.1 Clinical research1)The difference of the baseline data of the two groups of patients(gender,ASA classification,comorbid diseases,bleeding site,type of surgery,age,BMI,bleeding volume,amount of anesthetic drugs,operation time,time of hypotension,postoperative sedative drug consumption and mechanical ventilation time)was not statistically significant(P>0.05).Compared with preoperatively,the NIHHS of the two groups of patients was significantly decreased and GCS scores of the two groups of patients were significantly increased after operation(P<0.01),and there were no statistically significant differences in NIHHS scores and GCS scores between the two groups(P>0.05).2)Compared with Control group,the total effective rate of stress ulcer(the first endpoint)in the EA group was significantly increased(P<0.01).The success rate of gastric juice pH treatment in the EA group on the first,second and third days was significantly increased(P<0.05 or P<0.01).The positive rate of gastric occult blood test in the EA group was significantly reduced on the first and third days(P<0.05 or P<0.01).The positive rate of fecal occult blood test in the EA group on the third days was significantly lower(P<0.05);ICU stay time and hospital total stay time were significantly reduced(P<0.05 or P<0.01).3)Compared with T0,the serum repair factors(VEGF,HSP70 and TTF2)of the two groups were significantly increased(P<0.01 or P<0.05).Compared with Control group,the serum repair factor VEGF in the EA group was significantly increased at T2 and T3(P<0.01),and HSP70 was significantly increased at T1,T2 and T3(P<0.01 or P<0.05),and TTF2 was significantly increased at T1,T2,and T3(P<0.01).4)Compared with preoperatively,the HR,TP,LF、LF/HF of the EA group were significantly reduced(P<0.01 or P<0.05),HF was significantly increased(P<0.05),and the TP of the C group was significantly increased on the 5d postoperative day(P<0.01).Compared with group C,HR and LF/HF of EA group were significantly reduced(P<0.05),and HF was significantly increased(P<0.05).There were no statistically significant differences in TP and LF between the two groups(P>0.05).3.2 Basic experiment1)Compared with the Sham group,the gastric mucosal UI score of mice in the CRS group was significantly increased(P<0.001),and the repair factors(TFF2,VEGF,HSP70)were significantly increased(P<0.01);the gastric mucosal score of mice in the CRS+EA group was significantly higher increased(P=0.024),and the repair factors(TFF2,VEGF,HSP70)were significantly increased(P<0.01),and HIF-1αexpression was significantly increased(P<0.01);compared with CRS group,The UI score of CRA+EA group was significantly reduced(P=0.001),and the repair factors(TFF2,VEGF,HSP70)were significantly increased(P<0.01),and the expression of HIF-1α was significantly increased(P<0.01).2)Compared with the CRS+Vehicle group,the HIF-1α mRNA and protein levels in the CRS+PX478 group did not change significantly(P>0.05),and the expression levels of repair factors(TFF2,VEGF,HSP70)did not change significantly(P>0.05),The UI score of gastric mucosal damage did not change significantly(P>0.05).Compared with CRS+Vehicle+EA,HIF-1α mRNA and protein expression in the CRS+PX478+EA group were significantly reduced(P<0.01),and repair factors(TFF2,VEGF,HSP70)expression level was significantly reduced(P<0.01 or P<0.05),and gastric mucosal injury score(UI)was significantly increased(P<0.01).3)Compared with the CRS+Sham group,the expression level of HIF-1α mRNA and protein concentration in the CRS+VSD group did not change significantly(P>0.05),and the expression levels of group repair factors(TFF2,VEGF,HSP70)did not change significantly(P>0.05).and the mucosal injury score(UI)did not change significantly(P>0.05).Compared with the CRS+Sham+EA group,the expression level of HIF-1α mRNA and protein concentration in the CRS+VSD+EA group were significantly reduced(P<0.01),and the expression levels of the repair factors(TFF2,VEGF,HSP70)were significantly reduced(P<0.01),and the gastric mucosal injury score(UI)was significantly increased(P<0.01).4 Research conclusion4.1 Clinical researchElectroacupuncture has the effect of promoting the repair of stress ulcer damage in severe neurological disease,and this effect may be closely related to the regulation of vagus nerve function and the promotion of the release of repair factors.4.2 Basic experimentElectroacupuncture is mediated by the vagus nerve to regulate the expression level of HIF-1α,promote the release of its downstream repair factors(TFF2,VEGF,HSP70),and enhance the repair ability of the gastric mucosa after injury. |
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