Bradykinin Activates the Bradykinin B2 Receptor to Ameliorate Neuronal Injury in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury.

Guohui Yang, Pengfei Yao, Shengli Ma, Chi Zhang

ACS chemical neuroscience 2021 Mar 17

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Bradykinin and bradykinin B2 receptors (B2R) play important roles in both the peripheral and central nervous systems. The aim of this study was to explore the changes of bradykinin and B2R in spinal cord ischemic injury (SCII) and whether bradykinin treatment would improve the neurologic function of SCII rats. The rats were divided into the sham group, the SCII group, and three doses of bradykinin (50, 100, 150 μg/kg) groups. The neurologic function was assessed by the Basso, Beattie, and Bresnahan (BBB) score at -1, 1, 3, 5, and 7 days postsurgery. Bradykinin concentration in serum and IL-6, TNF-α, and MCP-1 levels in the spinal cord were detected by ELISA. The mRNA expressions of B2R, IL-6, TNF-α, MCP-1, COX-2, and iNOS in the spinal cord were determined by RT-PCR. The protein expressions of B2R, COX-2, iNOS, p65, and p-p65 were detected by Western blot. Immunohistochemical staining was used to examine B2R expression in the L4-6 segments of the spinal cord. Bradykinin levels in serum and B2R expression in the spinal cord were downregulated in SCII rats. Bradykinin treatment significantly improved the hind limb motor function of SCII rats and increased B2R expression, inhibiting COX-2, iNOS, and p-p65 expression in the spinal cord of SCII rats together with a decrease of the inflammatory mediators of IL-6, TNF-α, and MCP-1 levels. Bradykinin administration activated B2R in the spinal cord of SCII rats, which may improve hind limb locomotor recovery by regulating the NF-κB signaling pathway to inhibit the inflammatory response. These findings may provide a theoretical basis for the clinical application of bradykinin in SCII.

Citation

Guohui Yang, Pengfei Yao, Shengli Ma, Chi Zhang. Bradykinin Activates the Bradykinin B2 Receptor to Ameliorate Neuronal Injury in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury. ACS chemical neuroscience. 2021 Mar 17;12(6):1031-1038