右美托咪定调控miR-150-5p/P2X7受体轴减轻脑出血大鼠小胶质细胞活化

doi:10.3969/j.issn.1006-6233.2023.02.05

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Abstract Objective: To investigate the influence of dexmedetomidine (DEX) on the activation of microglia (MG) in rats with intracerebral hemorrhage (ICH) and its regulatory effect on miR-150-5p/P2X7 receptor (P2X7R) axis. Methods: Rats were separated into the sham group (n=12) and the model group (n=63). ICH rat model was established and included in the DEX low-dose group (25μg/kg), DEX high-dose group (50μg/kg), DEX (50μg/kg) +NC antagomir (20nmoL/L, 5μL) group and DEX (50μg/kg) + miR-150-5p antagomir (20nmoL/L, 5μL) group, with 12 rats in each group. The mode of administration was an intraperitoneal injection, once a day, 0.2mL each time, for 7 consecutive days. 24 h after the end of the administration, the neurological function was scored; the serum was separated, and the levels of serum TNF-ɑ and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA); the brain tissue of the bleeding area (CA2 region of hippocampus) was separated, and the brain tissue water content was measured, HE staining was applied to observe histopathological changes, immunofluorescence was applied to observe the morphology of MG, the qRT-PCR method was applied to detect the expression of miR-150-5p and P2X7R mRNA, Western blot method was applied to detect the protein expression of ionic calcium adaptor protein molecule-1 (Iba-1) and purinergic P2X7 receptor (P2X7R), and dual luciferase reporter gene experiment was applied to verify the targeting relationship between miR-150-5p and P2X7R. Results: Compared with the model group, the pathological changes of the brain tissue in the DEX low-dose and high-dose groups were gradually reduced, the infiltration of red blood cells and inflammatory cells was reduced, and the nuclear pyknosis phenomenon was reduced; the number of MG reduced obviously, and the cell body became smaller; the neurological function score and the expression of miR-150-5p in brain tissue were obviously increased (P<0.05); the levels of serum TNF-ɑ and IL-1β, brain tissue water content, and the expression of P2X7R mRNA and protein and Iba-1 protein in brain tissue were obviously reduced (P<0.05). Compared with the DEX high-dose group and DEX+NC antagomir group, a large number of red blood cells and inflammatory cell infiltration could be seen in the DEX+miR-150-5p antagomir group, the brain tissue structure and the arrangement of the cells were disordered; the number of MG was obviously increased, and the cell body became larger; the neurological function score and the expression of miR-150-5p in brain tissue were obviously decreased (P<0.05); the levels of serum TNF-ɑ and IL-1β, brain tissue water content, and the expression of P2X7R mRNA and protein and Iba-1 protein in brain tissue were obviously increased (P<0.05). The results of the dual luciferase reporter gene experiment showed that P2X7R was the downstream target gene of miR-150-5p. Conclusion: DEX can inhibit the activation of MG by up-regulating miR-150-5p and down-regulating P2X7R expression, and then play a protective role in ICH.

Key words： Dexmedetomidine miR-150-5p Purinergic P2X7 receptor Intracerebral hemorrhage Microglia

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2023.02.05 OR http://www.hbyxzzs.cn/EN/Y2023/V29/I2/200

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