CB2 receptor agonist JWH133 exerts protective effects on rat model of paraquat-induced acute lung injury
10.3969/j.issn.1000-4718.2014.12.011
- VernacularTitle:CB2受体激动剂JWH133对百草枯中毒致急性肺损伤大鼠的保护作用
- Author:
Zhenning LIU
;
Jun HAN
;
Qiang ZHENG
;
Min ZHAO
- Publication Type:Journal Article
- Keywords:
Paraquat;
Acute lung injury;
Cannaboid CB2 receptor;
Nuclear factor-κB;
Activator protein-1
- From:
Chinese Journal of Pathophysiology
2014;(12):2179-2184
- CountryChina
- Language:Chinese
-
Abstract:
[ ABSTRACT] AIM: To study the protective effects of cannabinoid CB2 receptor agonist JWH133 on rat acute lung injury induced by paraquat (PQ).METHODS: Male Sprague-Dawley rats (n=72) were randomly divided into 4 groups.PQ group:PQ was administered intraperitoneally at the dose of 20 mg/kg;Low-dose JWH133 pretreatment group ( L-JWH133 group):JWH133 (5 mg/kg, ip) was administered 1 h before PQ exposure;high-dose JWH133 pretreatment group ( H-JWH133 group):JWH133 (20 mg/kg, ip) was administered 1 h before PQ exposure;control group:1 mL sa-line was administered intraperitoneally.Arterial blood, bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected at 8 h, 1 d and 3 d after PQ exposure.PaO2 and the levels of TNF-αand IL-1βin BALF were measured via blood gas analyzer and ELISA, respectively.The pathological changes and lung injury scores were assessed at 3 d after PQ expo-sure.NF-κB and AP-1 protein levels were also determined by Western blotting.RESULTS:The decrease in PaO2 , struc-tural injury of the lung tissues, interstitial pulmonary edema, and the increase in IL-1βand TNF-αin BALF were observed in PQ-treated rats compared with control group.JWH133 pretreatment reduced the degree of lung tissue injury, decreased the levels of IL-1βand TNF-αin BALF and the NF-κB and AP-1 protein expression in the lung tissue compared with PQ group, especially in H-JWH133 group.CONCLUSION:CB2 receptor agonist JWH133 inhibits NF-κB and AP-1 protein expression in the lung tissues, and reduces the secretion of IL-1βand TNF-αin BALF after paraquat exposure, thus atten-uating paraquat-induced acute lung injury.