ABSTRACT
Background: Acute cerebral infarction (ACI), being the predominant form of stroke, presents challenges in terms of the limited effectiveness of various treatments in improving the neurological function. Although acupuncture shows promise in addressing ACI, the availability of high-quality evidence regarding its efficacy, safety, and underlying mechanism remains insufficient. In this study, we design a multicenter, prospective, single-blind, randomized controlled trial with the aim of evaluating the efficacy and safety of acupuncture for ACI, making an attempt to unveil the molecular mechanisms by proteomic. Methods: A total of 132 patients involving four hospitals will be randomized at a 1:1:1 ratio in the acupuncture group, control group, and sham acupuncture group. All the patients will receive basic treatment, and the patients in the acupuncture and sham acupuncture groups will also receive either acupuncture or sham acupuncture treatment, respectively, at six sessions each week for a 2 weeks period, followed by 3 months of follow-up. The primary outcome will be the change in the National Institute of Health Stroke Scale (NIHSS) scores after treatment. The secondary outcomes will include the Fugl-Meyer Assessment (FMA) scale scores and the Barthel Index (BI). Adverse events that occur during the trial will be documented. To discover differentially expressed proteins (DEPs) and their roles between the ACI subjects and healthy controls, we will also perform 4D-DIA quantitative proteomics analysis, and the DEPs will be confirmed by enzyme-linked immunosorbent assay (ELISA). This study was approved by the institutional review board of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (TYLL2023043). Written informed consent from patients is required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2300079204). Trial results will be published in a peer-reviewed academic journal. Discussion: The results of this study will determine the preliminary efficacy and safety of acupuncture in ACI patients and whether the mechanism of this form of non-pharmacologic stimulation is mediated by a novel therapeutic target for neurorehabilitation through our proteomic analysis. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2300079204.
ABSTRACT
OBJECTIVE: To observe the effect of manual acupuncture stimulation of "Shuigou" (GV26) and "Neiguan" (PC6) on neurological function and expression of Caspase-3 and Caspase-9 in brain tissues around the intracerebral hematoma in rats with acute intracerebral hemorrhage (ICH), so as to explore its possible mechanisms underlying improvement of ICH. METHODS: Ninety-six male SD rats were randomly divided into 4 groups: control, model, acupoint and non-acupoint (24 rats in each group). The ICH model was established by injection of the rat's autologous blood into the caudate nucleus. According to the time-points of 6, 24, 48 and 72 h after ICH, each of the 4 groups was further divided into 4 subgroups. For rats of the acupoint group, the PC6 on both sides was manually stimulated by manipulating the needle with lifting-thrusting-twisting reducing techniques, while the GV26 was stimulated with strong "sparrow-pecking" method for 10 times, then, left the needles in the acupoints for 30 min. For rats of the non-acupoint group, two non-acupoints: mid-spot below the bilateral axilla and the spot 3 mm above the left side of the coccyx tip were stimulated with the same methods to PC6 and GV26, respectively. For rats of the 6 h and 24 h subgroups, the intervention was given once after waking up from modeling, and for those of the 48 and 72 h subgroups, the intervention was conducted once a day for 2 or 3 times, respectively. The neurological severity score (NSS) was used to evaluate the degree of neurological function. The immunoactivity (expression) of Caspase-3 and Caspase-9 proteins of the hematoma focus of the brain was detected by immunohistochemistry. RESULTS: Following modeling, the NSS and the expression levels of Caspase-3 and Caspase-9 proteins in the brain tissues surrounding the hematoma at each time-points (6, 24, 48 and 72h) after modeling were significantly increased in the model group relevant to the control group (P<0.01, P<0.05). Compared with the model group, the NSS at 72h and the expression levels of Caspase-3 and Caspase-9 proteins at 6, 24, 48 and 72h were significantly down-regulated in the acupoint group (P<0.05) rather than in the non-acupoint group (P>0.05). CONCLUSION: Acupuncture of GV26 and PC6 can improve the neurological function in rats with ICH, which may be related to its function in reducing the expression of Caspase-3 and Caspase-9 proteins (apoptosis-related proteins) in the brain.