Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Dexmedetomidine pretreatment alleviates ischemia-reperfusion injury-induced inflammatory reaction via inhibition of TLR-4/NF-κB signaling pathway

Haiping Zhang¹, Zhiying Wu², Nanhuo Han¹, Lu Xu³, Kai Xiong¹

¹Department of Anesthesiology; ²Department of Radiotherapy, Nanchang 334 Hospital, No. 97, East 2nd Road, Xinxi Bridge, Qingyunpu District, Nanchang City, Jiangxi Province 330024; ³Resuscitation Room, The Fourth Affiliated Hospital of Nanchang University, Square South Road, Xihu District, Nanchang City, Jiangxi Province 330003, China.

For correspondence:- Kai Xiong Email: cnrj92@163.com

Accepted: 28 September 2019 Published: 31 October 2019

Citation: Zhang H, Wu Z, Han N, Xu L, Xiong K. Dexmedetomidine pretreatment alleviates ischemia-reperfusion injury-induced inflammatory reaction via inhibition of TLR-4/NF-κB signaling pathway. Trop J Pharm Res 2019; 18(10):2031-2035 doi: 10.4314/tjpr.v18i10.5

© 2019 The authors.
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Abstract

Purpose: To study the effect of dexmedetomidine on ischemia-reperfusion injury (IRI)–induced inflammatory response, as well as its underlying mechanism of action.

Methods: Three groups of healthy adult Sprague Dawley (SD) rats (mean weight, 275 ± 10 g): control, IRI and treatment groups were used. With the exception of control group, ligation was performed on left anterior descending coronary arteries for 30 min and blood perfusion was restored within 100 min to establish IRI. Control group rats were without left ligation. Rats in control and IRI groups received normal saline intraperitoneally 30 min prior to surgery, while the treatment group received 100 μg/kg dexmedetomidine via intraperitoneal injection 30 min before operation. Infarct volume was determined using triphenyl tetrazolium chloride (TTC) staining. IL-6) and TNF-α levels of myocardial tissues and serum were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine protein expressions of NF-ΚB and TLR-4 in myocardial tissues.

Results: Pretreatment with dexmedetomidine markedly decreased infarct volume caused by IRI (p < 0.05). Serum and myocardial TNF-α and IL-6 were significantly upregulated in IRI group, relative to control group, but were downregulated by pretreatment with dexmedetomidine (p < 0.05). There was marked upregulation of NF-ΚB and TLR-4 proteins in IRI rats, relative to untreated rats (p < 0.05). Dexmedetomidine also down-regulated the expressions of these proteins (p < 0.05).

Conclusion: Pretreatment with dexmedetomidine alleviates IRI-induced inflammatory reaction via suppression of TLR-4/NF-ΚB signaling pathway. This finding provides a basis for large-scale clinical trials with dexmedetomidine.

Keywords: Myocardial ischemia-reperfusion injury, Dexmedetomidine, Pretreatment, Inflammatory response