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

 目的:研究大麻素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。方法: 72只SD雄性大鼠随机平均分成4组。百草枯中毒组：按照20 mg/kg剂量腹腔注射；低剂量JWH133预处理组：在给予百草枯腹腔注射前1 h腹腔注射5 mg/kg JWH133；高剂量JWH133预处理组：在给予百草枯腹腔注射前1 h腹腔注射20 mg/kg JWH133；正常对照组：1 mL生理盐水腹腔注射。在注射百草枯后8 h、1 d和3 d时，收集动脉血、肺泡灌洗液和肺组织标本。采用血气分析仪测定动脉血氧分压（PaO2），采用ELISA方法检测支气管肺泡灌洗液中IL-1β和TNF-α含量，行组织切片HE染色进行肺损伤评分，利用Western blotting方法检测肺组织中NF-κB和AP-1 蛋白表达水平。结果: 与正常对照组相比，百草枯中毒组大鼠的动脉血PaO2明显下降，肺组织结构破坏，肺泡间质水肿，肺损伤指数增加，支气管肺泡灌洗液中炎性细胞因子IL-1β和TNF-α含量明显增加。JWH133预处理，尤其是高剂量JWH133可以减轻肺组织损伤程度，降低支气管肺泡灌洗液中IL-1β和TNF-α含量，减少肺组织中NF-κB和AP-1 蛋白的表达。结论: 应用CB2受体激动剂JWH133可以抑制百草枯中毒大鼠肺组织中NF-κB和AP-1 蛋白的表达，减少炎性细胞因子IL-1β和TNF-α的分泌，减轻百草枯中毒导致的急性肺损伤。

CB2 receptor agonist JWH133 exerts protective effects on rat model of paraquat-induced acute lung injury

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 saline 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-α and IL-1β in BALF were measured via blood gas analyzer and ELISA, respectively. The pathological changes and lung injury scores were assessed at 3 d after PQ exposure. NF-κB and AP-1 protein levels were also determined by Western blotting.RESULTS: The decrease in PaO2, structural injury of the lung tissues, interstitial pulmonary edema, and the increase in IL-1β and TNF-α in 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-1β and TNF-α in 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-1β and TNF-α in BALF after paraquat exposure, thus attenuating paraquat-induced acute lung injury.