1.Electroacupuncture improves gastrointestinal dyskinesia in rats with functional dyspepsia via PLC/IP3 pathway
Deqian YANG ; Qi CHEN ; Shuwen JIN ; Paidi XU
The Journal of Practical Medicine 2024;40(16):2284-2290
Objective This study aims to determine whether electroacupuncture regulates the phospholipase C(PLC)/inositol-1,4,5-trisphosphate(PLC/IP3)pathway in platelet-derived growth factor receptor α-positive(PDGFRα+)cells,thereby improving gastrointestinal motility disorders in functional dyspepsia(FD).Methods 40 SD rats were randomly divided into blank group,model group,electroacupuncture group,U73122(PLC inhibitor)group,and U73122+electroacupuncture group,with 8 rats in each group.Except for the blank group,all rats were subjected to multi-factor stress intervention to establish the FD model.After successful modeling,the U73122 group was given intraperitoneal injection of inhibitor,the electroacupuncture group was acupunctured at Zusanli and Taichong points,and the U73122+electroacupuncture group was injected with inhibitor 2 hours before acupunc-ture.Ten days later,gastrointestinal motility was tested;immunoblotting was used to detect the protein expression levels of PDGFRα,PLC,P-PLC,IP3;immunofluorescence was used to detect the average fluorescence density and co-localization expression of PDGFRα and PLC,IP3;electron microscope was used to observe the gap junction(GJ)situation in the gastric antrum area.Results After modeling,the gastrointestinal motility of rats was weakened,the protein expression levels of PDGFRα,PLC,and IP3 were significantly reduced,GJ widened,and cell morphol-ogy changed;compared with the model group,the gastrointestinal motility of rats in the electroacupuncture group,U73122 group,and U73122+electroacupuncture group was significantly improved,the expression levels of PDGFRα,PLC,P-PLC,IP3 increased,GJ was slightly tight,and cell morphology recovered;there was no significant difference in the expression levels of PDGFRα,PLC,P-PLC,IP3 in the gastric antrum of U73122 group and U73122+electroacupuncture group;PDGFRα,PLC,and IP3 had fluorescence co-localization.Conclusion Electroacupuncture can improve gastrointestinal dyskinesia in FD rats by activating the PLC/IP3 pathway in PDGFRα+cells.
2.Mechanism of Electroacupuncture in Functional Dyspepsia Rats Based on Hypothalamic-Pituitary-Adrenal Axis
Wei LE ; Hanling YAO ; Gege YANG ; Yisen WU ; Paidi XU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):259-267
Objective We aimed to explore the therapeutic mechanism of electroacupuncture at Yintang(EX-HN3),Neiguan(PC6)and Zusanli(ST36)on the Hypothalamic-Pituitary-Adrenal axis(HPA)of functional dyspepsia(FD)rats.Methods Forty SD rats were randomly divided into blank group,model group and EA group.The FD model was replicated by tail clamping,irregular diet,and filling the stomach with ice of Saline Solution.After modeling,the EA group received acupuncture treatment for 1 time day,30 minutes time,for 14 days.Recording the general state of the rat.Detection of locomotion and catatonia in rats by open field test.HE staining to observe the morphology and inflammation of gastric mucosa in rats.PCR detection of mRNA expression of 5-hydroxytryptamine3 receptor and corticotropin-releasing hormone in rat hypothalamus.Detection of corticotropin-releasing hormone receptor-2 and NOD-like receptor protein 6 inflammasome protein expression in rat duodenum by Western blotting.Alcian blue staining was used to detect the expression of rat duodenum goblet cells.Results Compared with the blank group,the general state,distance,speed,duodenum CRHR2 and NLRP6 proteins in the model group were significantly decreased(P<0.05),the hypothalamic 5-HT3R and CRH mRNA were significantly increased(P<0.05).Compared with the model group,the general state,distance,speed,expression of CRHR2,NLRP6 protein and goblet cells in the duodenum of rats in the EA group were significantly increased(P<0.05),the 5-HT3R and CRH mRNA in the hypothalamus were significantly decreased(P<0.05).In the model group,the connective tissue of the gastric mucosa was loosely arranged,the submucosa had mild edema,and there were some lymphocytes.The connective tissue of the gastric mucosa of the rats in the blank group and the electroacupuncture group was closely arranged,and there was no obvious proliferation of interstitial cells and no inflammatory cells.Conclusion EA can increase the expression of CRHR2,NLRP6 protein and goblet cells in the duodenum,and inhibit the expression of 5-HT3R and CRH in the hypothalamus.EA can improve gastrointestinal motility and locomotion,relieve anxiety,repair the mucosal barrier of the defective intestine,and restore the function of the Hypothalamic-Pituitary-Adrenal axis.
3.Effects of electroacupuncture at Zusanli on duodenal Caspase-1 and GSDMD of rats with functional dyspepsia
Jiabao LIU ; Shuwen JIN ; Zhaoxia KANG ; Yiming LIU ; Li ZHOU ; Feng SHEN ; Paidi XU ; Hongxing ZHANG ; Xiaoli PAN
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(12):1057-1063
Objective:To explore any effect of electroacupuncture (EA) at the Zusanli point on the scorch death of duodenal cells in rats with functional dyspepsia (FD) and possible mechanisms.Methods:Twenty-four 7-day-old Sprague-Dawley rats were randomly divided into a blank group, a model group and an EA group, each of 8. FD was induced in both the model and EA group rats using iodoacetamide gavage with tail-clip stimulation. After successful modeling the EA group was given acupuncture at the Zusanli point and then connected with a Korean acupuncture point nerve stimulator for 2 weeks. The other 2 groups were not given any intervention. The rats′ body weight was recorded before and after the modeling, as well as 7 and 14 days later. The gastric emptying rate and the small intestine propulsion rate of the three groups were detected right after the EA intervention, and the serum expression levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) were measured using enzyme-linked immunoassays. Real-time fluorescence quantitative polymerase chain reactions were used to detect the transcription levels of IL-1β and IL-6 in the rats′ duodenums, while western blotting was employed to assess the expression of caspase-1 P20 and dermatin D (GSDMD) in their duodenums.Results:After successful modeling, the average body weight of the rats in the model and EA groups was significantly different from that in blank group, and after 7 and 14 days the average body weight of the former groups was significantly different from that of the blank group, with significant differences between the two groups as well. After the EA intervention significant differences were observed in gastric reside and small intestine propulsion rate between the EA group and the model group, as well as between the model and the blank group. After the intervention, there were significant differences between the blank group and the other two groups in the average expression of IL-1β and IL-6 in serum, IL-1β and IL-6 mRNA in the duodenum, as well as the GSDMD and caspase-1 p20 proteins in the duodenum. There were significant differences between the model and EA groups in all of the above measurements.Conclusions:EA at the Zusanli point can significantly reduce the level of scorch death in the duodenum of FD rats, as well as relieve low-grade duodenal inflammation and the clinical symptoms of FD. Its mechanism may be related to the down-regulation of the expression of caspase-1 P20 and GSDMD-N protein, and of inflammatory factors such as IL-1β and IL-6, relieving low-grade duodenal inflammation.
4.To explore the application status and prospect of sham acupuncture in clinical trials of acupuncture based on 5G+VR technology
Yue LI ; Hongxing ZHANG ; Jing LI ; Paidi XU
International Journal of Traditional Chinese Medicine 2023;45(3):262-266
Acupuncture has been proved to be safe and effective by large-scale and authoritative clinical observation at home and abroad. However, in recent years, the results of some randomized controlled trials of acupuncture in JAMA showed no significant difference between acupuncture effect and sham acupuncture effect. Acupuncture and moxibustion in clinical practice is a summary of academic and clinical rules. Different from chemical drugs, the amount of stimulation, methods of operation and techniques vary. At present, sham acupuncture in clinical trials at home and abroad has been questioned by many scholars, who believe that sham acupuncture is not fake, and call for "fake targeted research" to be stopped. In order to improve the sham acupuncture control design, 5G + VR technology and the principle elements of sham acupuncture should be combined. We also discussed and analyzed advantages and prospects of modern intelligent medical technology of 5G + VR technology in the sham acupuncture RCT. We hope to promote standardization of acupuncture clinical trials, and the development, innovation and application of acupuncture research at home and abroad.
5.Effects of electroacupuncture at"Zusanli"and"Taichong"on gastrointestinal function and brain-gut axis in model rats with functional dyspepsia
Qiong WANG ; Yi ZHANG ; Ran ZOU ; Li ZHOU ; Min YANG ; Paidi XU
Journal of Beijing University of Traditional Chinese Medicine 2024;47(4):570-579
Objective We aimed to investigate the effects of electroacupuncture at"Zusanli"(ST36)and"Taichong"(LR3)on gastrointestinal motility,gastrointestinal hormones,and brain-gut axis in rats with functional dyspepsia(FD).Methods 48 SD rats were randomly divided into a normal control group,a model group,a cisapride group,and an electroacupuncture group,with 12 rats in each group.A mild tail pinch stimulation combined with intermittent food deprivation was used to establish the FD rat model.Body mass,food intake,and sucrose preference rate were recorded before and after modeling to verify the success of the FD model.After modeling,the normal control group and the model group received no intervention;the cisapride group rats were administered cisapride[0.4 g/(kg·d)]by intragastric perfusion for 6 consecutive days as one course of treatment,with a rest day between each course;the electroacupuncture group rats received electroacupuncture stimulation at bilateral"Zusanli"and"Taichong"(DC,dense-sparse wave,2/100 Hz,2-5 mA.Electricity was applied for 30 min),with stimulation every 24 h for 6 consecutive times as one course of treatment,with a rest day between each course.After two courses of treatment,samples were collected to compare gastrointestinal motility indices,blood levels of gastrointestinal hormones[motilin,gastrin,serotonin(5-HT),nitric oxide(NO)],serum and tissue levels of endogenous brain-gut peptides[cholecystokinin(CCK),calcitonin gene-related peptide(CGRP),neuropeptide Y(NPY)]in the hypothalamus,gastric antrum,duodenum,colon,and protein expressions of ghrelin and substance P in the hypothalamus,spinal cord,gastric antrum,and colon.Results Body mass,food intake,and sucrose preference rate were lower of the model rats than those of the normal rats(P<0.05).Compared with the model group,rats in the electroacupuncture group and cisapride group had(i)lower gastric residual rates,higher rates of small intestinal propulsion and gastric slow wave main frequency and power(P<0.05);(ii)levels of motilin,gastrin,and 5-HT increased,while NO level decreased(P<0.05);(iii)serum CCK content increased,while CGRP and NPY levels decreased(P<0.05);(iv)CCK protein positive expression increased,while CGRP and NPY protein positive expression decreased in the hypothalamus,gastric antrum,duodenum(P<0.05);(v)ghrelin protein expressions increased,and substance P protein expression decreased in the hypothalamus,spinal cord,gastric antrum,and colon(P<0.05).There were no significant differences in these indicators between the electroacupuncture group and the cisapride group.Conclusion Electroacupuncture at"Zusanli"and"Taichong"can effectively alleviate gastrointestinal motility disorders in FD rats,regulate gastrointestinal hormone levels,reverse abnormal brain-gut peptide expression,and regulate brain-gut interaction balance.
6.Electroacupuncture activates phosphorylated AMPKαto regulate the expression of the mTOR gene in rats with functional dyspepsia
Lei TANG ; Hongxing ZHANG ; Paidi XU ; Zhaoxia KANG
Chinese Journal of Physical Medicine and Rehabilitation 2018;40(11):809-813
Objective To investigate how electroacupuncture activates the AMPKαpathway in the treatment of functional dyspepsia ( FD) . Methods Tail clipping stimulation was combined with an irregular diet to induce FD in 20 Sprague-Dawley rats. They were randomly divided into a model group and an electroacupuncture group, each of 10. Ten others had no FD induced and formed a normal group. The rats in the electroacupuncture group were given 10 days of electroacupuncture treatment, while those in the normal and model groups were restrained and fixed like those in the electroacupuncture group, but not given electroacupuncture. The expression of phosphorylated adenosine mono-phosphate-activated protein kinase alpha (p-AMPKα), phosphorylated tuberin (p-TSC2) and Rheb protein in the stomachs and small intestines of each group were detected using the western blotting. Levels of mTOR mRNA were quantified using the reverse-transcription polymerase chain reaction ( RT-PCR) . Results The western blotting re-sults showed that compared with the normal group, the expression levels of p-AMPKα and p-TSC2 in the stomachs and small intestines of the model group decreased significantly, while that of Rheb protein increased significantly. Compared with the model group, the expression of p-AMPKαand p-TSC2 increased significantly after the electroacu-puncture treatment, while that of Rheb protein decreased significantly. According to the RT-PCR results, the expres-sion of mTOR mRNA in the stomachs and small intestines of the model group was up-regulated significantly compared with the normal group. Compared with the model group, expression of mTOR mRNA in the electroacupuncture group was significantly down-regulated. Conclusion Electroacupuncture can activate the AMPKα pathway, up-regulate the expression of the related protein p-TSC2, and decrease the expression of Rheb protein, thereby down-regulating the transcription of the mTOR gene. That would serve to treat FD.