Objective:To investigate the mechanism of JAK2/STAT3/SOCS1 signaling pathway in electroacupuncture of different acupoints on acute colitis rats.Methods:36 SPF SD rats were randomly divided into 6 groups,with 6 rats in...Objective:To investigate the mechanism of JAK2/STAT3/SOCS1 signaling pathway in electroacupuncture of different acupoints on acute colitis rats.Methods:36 SPF SD rats were randomly divided into 6 groups,with 6 rats in each group.The rat model of acute colitis was prepared by enema with glacial acetic acid solution.After the model was established,electroacupuncture was given to each acupoint group,with density wave,frequency 2Hz-50 Hz,intensity 2 mA,muscle tremor as the degree 20 min/time,1 time/day,for 3 consecutive days.Observe the general condition of rats;the pathological changes of colonic mucosa in rats were observed by HE method.The contents of serum interleukin-4(IL-4)and interleukin-8(IL-8)were detected by ELISA.Western blot and RT-PCR were used to detect the expression of JAK2,STAT3,SOCS1 protein and mRNA in rat colon tissue.Results:In contrast to the normal group,the overall condition of the model group was worse,the colonic mucosa was severely damaged,even necrotic,and the ulcer surface was obvious.The content of IL-4 in serum was obviously reduced,and the content of IL-8 was obviously go up(P<0.01).The protein content of JAK2,STAT3 and the expression of JAK2,STAT3 mRNA in colon tissue of rats were obviously go up,while the protein content of SOCS1 and the expression of SOCS1 mRNA were obviously reduced(P<0.01).In contrast to the model group,the general condition of rats in each acupoint group was significantly improved,the damage and necrosis of colonic mucosa and ulcer surface were obviously alleviated,the content of IL-4 in serum was obviously go up,and the content of IL-8 was significantly decreased(P<0.01).The protein content of JAK2,STAT3 and the expression of JAK2,STAT3 mRNA in colon tissue of rats were obviously reduced,while the protein content of SOCS1 and the expression of SOCS1 mRNA were obviously go up(P<0.05,P<0.01).Comparison of different acupoint groups,the colonic mucosal injury in the Zusanli group was significantly reduced,the content of serum IL-4 was significantly increased,and the content of IL-8 was significantly decreased(P<0.05,P<0.01).The protein content and mRNA expression of JAK2 and STAT3 in colon tissue were significantly down-regulated,while the protein content and mRNA expression of SOCS1 were significantly go up(P<0.05,P<0.01).Conclusion:Electroacupuncture at each acupoint can improve the damage of colonic mucosa and reduce the inflammatory response.The therapeutic effect of Zusanli(ST36)is better than that of Tianshu(ST25),Dachangshu(BL25)and Shangjuxu(ST37).The mechanism may be related to the regulation of JAK2/STAT3/SOCS1 signaling pathway related proteins and inflammatory cytokines IL-4 and IL-8.展开更多
BACKGROUND Restoration of immune homeostasis by targeting the balance between memory T helper(mTh)cells and memory follicular T helper(mTfh)cells is a potential therapeutic strategy against ulcerative colitis(UC).Beca...BACKGROUND Restoration of immune homeostasis by targeting the balance between memory T helper(mTh)cells and memory follicular T helper(mTfh)cells is a potential therapeutic strategy against ulcerative colitis(UC).Because of its anti-inflammatory and immunomodulatory properties,curcumin(Cur)is a promising drug for UC treatment.However,fewer studies have demonstrated whether Cur can modulate the mTh/mTfh subset balance in mice with colitis.AIM To explore the potential mechanism underlying Cur-mediated alleviation of colitis induced by dextran sulfate sodium(DSS)in mice by regulating the mTh and mTfh immune homeostasis.METHODS Balb/c mice were administered 3%and 2%DSS to establish the UC model and treated with Cur(200 mg/kg/d)by gavage on days 11-17.On the 18th d,all mice were anesthetized and euthanized,and the colonic length,colonic weight,and colonic weight index were evaluated.Histomorphological changes in the mouse colon were observed through hematoxylin-eosin staining.Levels of Th/mTh and Tfh/mTfh cell subsets in the spleen were detected through flow cytometry.Western blotting was performed to detect SOCS-1,SOCS-3,STAT3,p-STAT3,JAK1,p-JAK1,and NF-κB p65 protein expression levels in colon tissues.RESULTS Cur effectively mitigates DSS-induced colitis,facilitates the restoration of mouse weight and colonic length,and diminishes the colonic weight and colonic weight index.Simultaneously,it hinders ulcer development and inflammatory cell infiltration in the colonic mucous membrane.While the percentage of Th1,mTh1,Th7,mTh7,Th17,mTh17,Tfh1,mTfh1,Tfh7,mTfh7,Tfh17,and mTfh17 cells decreased after Cur treatment of the mice for 7 d,and the frequency of mTh10,Th10,mTfh10,and Tfh10 cells in the mouse spleen increased.Further studies revealed that Cur administration prominently decreased the SOCS-1,SOCS-3,STAT3,p-STAT3,JAK1,p-JAK1,and NF-κB p65 protein expression levels in the colon tissue.CONCLUSION Cur regulated the mTh/mTfh cell homeostasis to reduce DSS-induced colonic pathological damage,potentially by suppressing the JAK1/STAT3/SOCS signaling pathway.展开更多
基金Natural Science Foundation of Shanxi Province(No.201801D121358)"Basic Research Special Project"of Shanxi University of Tradit Chin Med Science and Technology Innovation Ability Cultivation Program(No.2021PY-JC-13)。
文摘Objective:To investigate the mechanism of JAK2/STAT3/SOCS1 signaling pathway in electroacupuncture of different acupoints on acute colitis rats.Methods:36 SPF SD rats were randomly divided into 6 groups,with 6 rats in each group.The rat model of acute colitis was prepared by enema with glacial acetic acid solution.After the model was established,electroacupuncture was given to each acupoint group,with density wave,frequency 2Hz-50 Hz,intensity 2 mA,muscle tremor as the degree 20 min/time,1 time/day,for 3 consecutive days.Observe the general condition of rats;the pathological changes of colonic mucosa in rats were observed by HE method.The contents of serum interleukin-4(IL-4)and interleukin-8(IL-8)were detected by ELISA.Western blot and RT-PCR were used to detect the expression of JAK2,STAT3,SOCS1 protein and mRNA in rat colon tissue.Results:In contrast to the normal group,the overall condition of the model group was worse,the colonic mucosa was severely damaged,even necrotic,and the ulcer surface was obvious.The content of IL-4 in serum was obviously reduced,and the content of IL-8 was obviously go up(P<0.01).The protein content of JAK2,STAT3 and the expression of JAK2,STAT3 mRNA in colon tissue of rats were obviously go up,while the protein content of SOCS1 and the expression of SOCS1 mRNA were obviously reduced(P<0.01).In contrast to the model group,the general condition of rats in each acupoint group was significantly improved,the damage and necrosis of colonic mucosa and ulcer surface were obviously alleviated,the content of IL-4 in serum was obviously go up,and the content of IL-8 was significantly decreased(P<0.01).The protein content of JAK2,STAT3 and the expression of JAK2,STAT3 mRNA in colon tissue of rats were obviously reduced,while the protein content of SOCS1 and the expression of SOCS1 mRNA were obviously go up(P<0.05,P<0.01).Comparison of different acupoint groups,the colonic mucosal injury in the Zusanli group was significantly reduced,the content of serum IL-4 was significantly increased,and the content of IL-8 was significantly decreased(P<0.05,P<0.01).The protein content and mRNA expression of JAK2 and STAT3 in colon tissue were significantly down-regulated,while the protein content and mRNA expression of SOCS1 were significantly go up(P<0.05,P<0.01).Conclusion:Electroacupuncture at each acupoint can improve the damage of colonic mucosa and reduce the inflammatory response.The therapeutic effect of Zusanli(ST36)is better than that of Tianshu(ST25),Dachangshu(BL25)and Shangjuxu(ST37).The mechanism may be related to the regulation of JAK2/STAT3/SOCS1 signaling pathway related proteins and inflammatory cytokines IL-4 and IL-8.
基金Supported by the National Natural Science Foundation of China,No.81760808 and No.82260863Scientific and Technological Project of Education Department of Jiangxi Province,No.GJJ181582+1 种基金Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program,No.CXTD22008Key Laboratory of Pharmacodynamics and Quality Evaluation on anti-Inflammatory Chinese Herbs,Jiangxi Administration of Traditional Chinese Medicine,No.202208.
文摘BACKGROUND Restoration of immune homeostasis by targeting the balance between memory T helper(mTh)cells and memory follicular T helper(mTfh)cells is a potential therapeutic strategy against ulcerative colitis(UC).Because of its anti-inflammatory and immunomodulatory properties,curcumin(Cur)is a promising drug for UC treatment.However,fewer studies have demonstrated whether Cur can modulate the mTh/mTfh subset balance in mice with colitis.AIM To explore the potential mechanism underlying Cur-mediated alleviation of colitis induced by dextran sulfate sodium(DSS)in mice by regulating the mTh and mTfh immune homeostasis.METHODS Balb/c mice were administered 3%and 2%DSS to establish the UC model and treated with Cur(200 mg/kg/d)by gavage on days 11-17.On the 18th d,all mice were anesthetized and euthanized,and the colonic length,colonic weight,and colonic weight index were evaluated.Histomorphological changes in the mouse colon were observed through hematoxylin-eosin staining.Levels of Th/mTh and Tfh/mTfh cell subsets in the spleen were detected through flow cytometry.Western blotting was performed to detect SOCS-1,SOCS-3,STAT3,p-STAT3,JAK1,p-JAK1,and NF-κB p65 protein expression levels in colon tissues.RESULTS Cur effectively mitigates DSS-induced colitis,facilitates the restoration of mouse weight and colonic length,and diminishes the colonic weight and colonic weight index.Simultaneously,it hinders ulcer development and inflammatory cell infiltration in the colonic mucous membrane.While the percentage of Th1,mTh1,Th7,mTh7,Th17,mTh17,Tfh1,mTfh1,Tfh7,mTfh7,Tfh17,and mTfh17 cells decreased after Cur treatment of the mice for 7 d,and the frequency of mTh10,Th10,mTfh10,and Tfh10 cells in the mouse spleen increased.Further studies revealed that Cur administration prominently decreased the SOCS-1,SOCS-3,STAT3,p-STAT3,JAK1,p-JAK1,and NF-κB p65 protein expression levels in the colon tissue.CONCLUSION Cur regulated the mTh/mTfh cell homeostasis to reduce DSS-induced colonic pathological damage,potentially by suppressing the JAK1/STAT3/SOCS signaling pathway.
