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Genome-Wide Transcription Analysis of Electroacupuncture Precondition-Induced Ischemic Tolerance on SD Rat With Ischemia-Reperfusion Injury.

ABSTRACT: Acupuncture promotes the recovery of neurological function by the overall improvement of ischemic brain injury. It is not only regarded as a rehabilitative treatment but also a pretreatment method for stroke. However, its mechanism has not been fully elucidated. In this study, rats were treated with electroacupuncture (EA) at Baihui (GV20) for 30 min/day for 6 days, ahead of conducting cerebral ischemia-reperfusion (I/R) injury. Infarction volume, Evans blue leakage, and neurological deficits were evaluated at 24 h after I/R injury. Then, the ipsilateral ischemic brain was isolated for RNA sequencing (RNA-Seq) to identify molecular consequences. The results showed that EA pretreatment decreased blood-brain barrier (BBB) permeability, reduced brain infarction volume, and improved neurological outcomes. EA pretreatment could upregulate expression of antivirus and immunity activity-associated genes (such as Ifit1, Ifit3, Irf7, and Oasla) and downregulate expression of matrix disruption-associated genes (Col24a1, Col11a1, Col27a1, etc.) in healthy rats. In addition, it could partially reverse or ameliorate genome-wide transcription changes of the ipsilateral ischemic brain. For the first time, this study provides insight into genomic network modulation of a healthy rat with EA treatment and a EA-preconditioned rat under subsequent I/R injury, which is helpful in explaining acupuncture precondition-induced ischemic tolerance of stroke. It also provides new strategies and targets for the prevention of ischemic stroke.

SUBMITTER: Fu S

PROVIDER: S-EPMC8415365 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRemote ischemic preconditioning (RIPC) is a phenomenon, whereby repeated, non-lethal episodes of ischemia to an organ or limb exert protection against ischemia-reperfusion (I/R) injury in distant organs. Despite intensive research, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms, especially in the intestine. Aim of this study was to evaluate possible protective effects RIPC on intestinal I/R injury.MethodsThirty rats were randomly assigned to four groups: I/R; I/R + RIPC; Sham; Sham + RIPC. Animals were anesthetized and the superior mesenteric artery was clamped for 30 min, followed by 60 min of reperfusion. RIPC-treated rats received 3 × 5 min of bilateral hindlimb I/R prior to surgery, sham groups obtained laparotomy without clamping. After I/R injury serum/tissue was analyzed for: Mucosal damage, Caspase-3/7 activity, expression of cell stress proteins, hydrogen peroxide (H2O2) and malondialdehyde (MDA) production, Hypoxia-inducible factor-1α (HIF-1α) protein expression and matrix metalloproteinase (MMP) activity.ResultsIntestinal I/R resulted in increased mucosal injury (P < 0.001) and elevated Caspase-3/7 activity (P < 0.001). RIPC significantly reduced the histological signs of intestinal I/R injury (P < 0.01), but did not affect Caspase-3/7 activity. Proteome profiling suggested a RIPC-mediated regulation of several cell stress proteins after I/R injury: Cytochrome C (+ 157%); Cited-2 (- 39%), ADAMTS1 (+ 74%). Serum concentrations of H2O2 and MDA remained unchanged after RIPC, while the reduced intestinal injury was associated with increased HIF-1α levels. Measurements of MMP activities in serum and intestinal tissue revealed an attenuated gelatinase activity at 130 kDa within the serum samples (P < 0.001) after RIPC, while the activity of MMPs within the intestinal tissue was not affected by I/R injury or RIPC.ConclusionsRIPC ameliorates intestinal I/R injury in rats. The underlying mechanisms may involve HIF-1α protein expression and a decreased serum activity of a 130 kDa factor with gelatinase activity.

Dataset Information

Genome-Wide Transcription Analysis of Electroacupuncture Precondition-Induced Ischemic Tolerance on SD Rat With Ischemia-Reperfusion Injury.

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