1.Department of Anesthesiology, the First Hospital of Lanzhou University, Lanzhou 730000, China 2.Class One Grade 2015 Clinical Medicine, the First Clincial Medical College of Lanzhou University, Lanzhou 730000, China
Objective Detect the expression level of HMGB1,TLR4,TNF-α,IL-1β and IL-10 in spinal cord tissue of neuropathic pain model rat after tanshinone ⅡA treated to explore its effect on neuropathic pain and the mechanisms. Methods A total of 54 males Sprague-Dawley (SD) rats were randomly divided into three groups:sham-operated group , model control group, and Tan ⅡA group.Tan ⅡA was administered intraperitoneally to rats in Tan ⅡA group at a dose of 30 mg·kg-1 daily for 14 days after surgery.The pain threshold was measured 1 day before SNL (baseline) and 3, 7, and 14 days after surgery.The expressions of HMGB1, TLR4 mRNA and protein in lumbar spinal cord 4-6(L4-L6) were assessed by RT-PCR and Western blotting, respectively.The levels of TNF-α, IL-1β and IL-10 in the spinal cord were detected by ELISA. Results The paw withdrawl threshold (PWT) and paw withdrawl latency (PWL) were significantly decreased after SNL (P<0.05) .The expressions of TLR4, HMGB1 mRNA and protein were significantly increased (P<0.05),and the levels of TNF-α, IL-1β were significantly increased after SNL compared with those in the sham-operated group (P<0.05).After Tan ⅡA treatment, HMGB1 and TLR4 mRNA and protein levels were reduced significantly (P<0.05).TNF-α and IL-1β were downregulated, but IL-10 was upregulated in the spinal cords of SNL-induced rats (P<0.05),which was accompanied by improvement of pain behaviours in the Tan ⅡA group (P<0.05). Conclusion These results indicate Tanshinone ⅡA inhibited SNL-induced neuropathic pain via multiple effects, the possible mechanism is that HMGB1-TLR4 signal transduction pathway and its downstream cytokines are inhibited at the molecular level.It also suggesting that HMGB1-TLR4 signal transduction pathway may be related to neuropathic pain and is a target for the treatment of neuropathic pain.
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