Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (9): 59-66.doi: 10.6040/j.issn.1671-7554.0.2021.1383

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Effects and mechanism of overexpression of miR-27a on hippocampal neuronal injury in rats with acute cerebral infarction

ZOU Pinheng1, CHEN Tianguo1, HU Kang2, LI Weicai3   

  1. 1. Department of Clinical Laboratory;
    2. Department of Internal Medicine-Neurology;
    3. Department of Emergency, The Third Affiliated Hospital of Hengyang Medical College, University of South China, Hengyang 421900, Hunan, China
  • Published:2022-09-02

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Abstract: Objective To investigate the effects of miR-27a overexpression on hippocampal neuron injury in rats with acute cerebral infarction(ACI)and its possible mechanism. Methods A total of 60 SD rats were randomly divided into sham operation group(Sham group), Model group, agomir negative control group(Agomir-NC group)and miR-27a agomir group(Agomir group), with 15 rats in each group. Modified Longa thread embolization method was used to establish the rat models of ACI. One day before modeling and the time when modeling was successful, 15 mg/kg agomir-NC or miR-27a agomir were injected through the lateral ventricle. The neurological deficits of rats were evaluated with Zea-Longa score 72 h after operation. The cerebral infarct size of rats was measured with triphenyltetrazole chloride(TTC)staining. The apoptosis level of hippocampal tissue was detected with TUNEL. The expression of miR-27a in the hippocampus was detected with qRT-PCR. The percentage of Iba-1+/CD68+ microglia in the hippocampus was detected with flow cytometry(FCM). The levels of IL-1β, IL-6, TNF-α and iNOS in hippocampus were detected with enzyme-linked immunosorbent assay(ELISA). The expressions of toll-like receptor 4(TLR4)signaling pathway related proteins including TLR4, MyD88, p-NF-κB p65 and NF-κB p65 in hippocampus were detected with Western blotting. Results Compared with Sham group, the Model group had significantly increased apoptosis of hippocampal cells and level of Iba-1+/CD68+ microglia(P<0.001), and significantly increased levels of IL-1β, IL-6, TNF-α and iNOS and protein expressions of TLR4, MyD88 and p-NF-κB p65(P<0.05), but significantly decreased expression of miR-27a(P<0.001). Compared with Model group, the agomir group had significantly decreased neurological deficits score, cerebral infarction area, apoptosis level of hippocampal cells and level of Iba-1+/CD68+ microglia(P<0.001), and significantly decreased levels of IL-1β, IL-6, TNF-α and iNOS and protein expressions of TLR4, MyD88 and p-NF-κB p65(P<0.05), but significantly increased expression of miR-27a(P<0.001). Conclusion Overexpression of miR-27a can alleviate hippocampal neuronal injury in ACI rats by inhibiting microglia M1-type polarization, and the mechanism may be related to the inhibition of TLR4/NF-κB signaling pathway.

Key words: miR-27a, Acute cerebral infarction, Microglia cells, TLR4/NF-κB signaling pathway

CLC Number: 

  • R743.33
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