Rutaecarpine protects against myocardial ischemia / reperfusion injury through inhibiting Toll-like receptor 4 / NF-κB signaling pathway in rats / 中国药理学通报

ABSTRACT

Aim To investigate whether the protection of rutaecarpine against myocardial ischemia / reperfusion (I/ R ) injury is mediated by Toll-like receptor 4 (TLR4)/ NF-κB pathway,and whether these effects are related to the release of calcitonin gene-related peptide(CGRP)in plasma. Methods Sprague-Daw-ley rats were subjected to 60 min of ligation of the left anterior descending coronary followed by 3h of reperfu-sion to induce I/ R injury. Rats were pretreated with rutaecarpine 10 min before the ligation,and some rats were pretreated with capsazepine 2 min before rutae-carpine administration. Myocardial infarct size,CGRP concentration in plasma and creatine kinase (CK)ac-tivity in serum were measured. The expression of TLR4 mRNA in myocardial tissue was determined by RT-PCR. The protein expression of TLR4 and NF-κB in myocardial tissue was analyzed by immunohistochemis-try. Results Rutaecarpine (100,300 μg · kg - 1 , iv)significantly reduced the infarct size and the serum CK activity concomitantly with the increase in plasma CGRP concentration (P < 0. 05). Importantly,the ex-pression of TLR4 (both mRNA and protein)and NF-κB (protein)was increased by myocardial I/ R injury, and dramatically inhibited by rutaecarpine pretreatment (P < 0. 05). All these effects of rutaecarpine were a-bolished by capsazepine (1. 5 mg·kg - 1 ,iv),a spe-cific antagonist for vanilloid receptor-1. Conclusion Rutaecarpine protects against myocardial I/ R injury by inhibiting TLR4 / NF-κB pathway,which is related to the increased release of CGRP.