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OBJECTIVE@#To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways.@*METHODS@#Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot.@*RESULTS@#Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P<0.05). The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture (P<0.05 or P<0.01). In addition, the extracellular signal-regulated kinase (ERK) and p38 signaling pathways were inhibited by bloodletting puncture (P<0.05).@*CONCLUSIONS@#Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways. Therefore, bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.
ABSTRACT
Due to its own internal laws of development, Chinese medicine (CM) seems more inclined to empirical medicine in a relatively long historical period. It is considered to be lacking objective and unified clinical practice guidelines (CPGs), and the difficulties in diagnosis and therapeutic effect evaluation comes with it, have restricted its further inheritance, development and international communication. Over the years, our research group has been committed to improving the standardization theory and methodology of CM, also perfecting relative techniques for further application, which are all based on the stratified evidence scoring method. We have already applied this method to 45 issued guidelines, including 5 national guidelines, 3 industrial guidelines, and 37 formulation/revision social organization guidelines. The stratified evidence scoring method has been recognized and used widely. It helps scholars and applicators to study, formulate, publish and popularize the acupuncture therapy clinical practice guidelines better, thus further promotes the development of acupuncture therapy.
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OBJECTIVE@#To identify the prominent molecular signaling in acupoints and explore their roles in initiating the analgesia effect of manual acupuncture (MA).@*METHOD@#A three-step study was conducted, the experiment 1 was a genome-wide analysis of the tissue at acupoint Zusanli (ST 36), including 12 Wistar rats which were divided into control, control+MA1, and control+MA7 groups. In the experiment 2, the paw withdrawal latency (PWL), immunohistochemistry and Western blot analysis of phospho-nuclear factor kappa B (NFκB) p65 (p-p65), phospho-NFκB p50 (p-p50) at ST 36 were performed on rats of saline, saline+MA, and complete Freund's adjuvant (CFA)+MA groups (n=6). In experiment 3, 24 rats were divided into saline+DMSO, CFA+DMSO, CFA+DMSO+MA, and CFA+BAY 11-7082+MA groups, the PWL and immunofluorescence assay of NFκB p65 at ST 36 was conducted.@*RESULT@#(1) The gene: inhibitor of NFκB (Nfkbia), interleukin-1β (Il1b), interleukin-6 (Il6), chemokine c-x-c motif ligand 1 (Cxcl1), monocyte chemoattractant protein-1 (MCP-1/Ccl2) expressions in the control+MA7 group were significantly increased (P<0.05 or P<0.01), and the expression of NFκB p65 (Rela), NFκB p50 (Nfkb1) were increased in the control+MA7 group (P<0.05). (2) CFA+MA groups showed increased PWL from day 1 to 7 (P<0.01 vs. CFA), and the Western blot results were consistent with immunohistochemistry, the expression of NFκB p-p65 and NFκB p-p50 were significantly increased in the MA-related groups compared with control and CFA groups (P<0.05). (3) Compared with the CFA+DMSO+MA group, the PWL of the CFA+ BAY 11-7082+MA group decreased significantly and continued until day 5 and 7 (P<0.05 and P<0.01, respectively), and the NFκB p65 expression of CFA+BAY 11-7082+MA was significantly reduced compared with CFA+DMSO+MA (P<0.01).@*CONCLUSION@#Local NFκB signaling cascade in acupoint caused by MA is an important step in initiating the analgesic effect, which would provide new evidence for the initiation of MA-effect and improve the understanding of the scientific basis of acupuncture analgesia.
Subject(s)
Animals , Rats , Acupuncture Analgesia , Acupuncture Points , Electroacupuncture , NF-kappa B/metabolism , Rats, Sprague-Dawley , Rats, Wistar , Signal TransductionABSTRACT
The indication of bloodletting therapy was determined based on the multi-dimensional evidence assessment, which could provide guidance for the clinical application of bloodletting therapy. The literature of bloodletting therapy was comprehensively collected by retrieval in CNKI, Wanfang and VIP databases (until February 23, 2019), modern books in Library of Tianjing University of TCM and the (Fifth Edition). The disease spectrum of bloodletting therapy was determined by self-designed questionnaire survey e-mailed to relevant experts. The indication of bloodletting therapy was determined by Delphi expert meeting. As a result, 746 pieces of ancient literature and 32 775 modern literature were included. The indications of bloodletting therapy based on the multi-dimensional evidence assessment include herpes zoster, acne, acute tonsillitis, vascular headache, varicose veins of lower extremities, acute lumbar sprain, early erysipelas, wheat swelling, exogenous fever of children, stroke, which are mainly the syndromes of blood stasis, toxin, excess and heat.
Subject(s)
Humans , Bloodletting , Medicine, Chinese TraditionalABSTRACT
Objective: To summarize the research status of the changes in local microenvironment of acupoints caused by acupuncture, provide theoretical guidance for the initiation mechanisms of local acupuncture effect at acupoints. Methods: Using acupuncture, acupoint as key words to search China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), PubMed and other databases, the representative articles were selected for review. Results: Acupuncture could excite afferent nerves, activate cells, and promote the release of chemical substances like neuropeptide, hormone, cytokines, etc. in the local site of acupoints. Besides, it may cause mechanical deformation of connective tissues, and change chemical ions as well as ion channels. Conclusion: The microenvironment changes around acupoints are crucial to acupuncture effect; the concept of 'acupoints network' can be used to objectively describe the local changes around the acupoints after acupuncture.
ABSTRACT
The inflammasome is an emerging new pathway in innate immune defense against microbial infection or endogenous danger signals. The inflammasome stimulates activation of inflammatory caspases, mainly caspase-1. Caspase-1 activation is responsible for processing and secretion of IL-1β and IL-18 as well as for inducing macrophage pyroptotic death. Assembly of the large cytoplasmic inflammasome complex is thought to be mediated by members of NOD-like receptor (NLR) family. While functions of most of the NLR proteins remain to be defined, several NLR proteins including NLRC4 have been shown to assemble distinct inflammasome complexes. These inflammasome pathways, particularly the NLRC4 inflammasome, play a critical role in sensing and restricting diverse types of bacterial infections. Here we review recent advances in defining the exact bacterial ligands and the ligand-binding receptors involved in NLRC4 inflammasome activation. Implications of the discovery of the NAIP family of inflammasome receptors for bacterial flagellin and type III secretion apparatus on future inflammasome and bacterial infection studies are also discussed.