摘要
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 m L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(Pa O2),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Pa O2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。
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） ： JWHI33 （5 mg/kg, ip） was administered I h before PQ exposure; high-dose JWHI33 pretreatment group （ H-JWHI33 group） ： JWHI33 （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. PaOz and the levels of TNF-ct and IL-113 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 expo- sure. NF-KB 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-113 and TNF-ot 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-113 and TNF-ct in BALF and the NF-KB and AP-1 protein expression in the lung tissue oompared with PQ group, especially in H-JWH133 group. CONCLUSION： CB2 receptor agonist JWHI33 inhibits NF-KB and AP-1 protein expression in the lung tissues, and reduces the secretion of IL-113 and TNF-et in BALF after paraquat exposure, thus atten- uating paraquat-induced acute lung injury.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2014年第12期2179-2184,共6页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81171793/H1503)
辽宁省科学计划项目(No.201102278)
辽宁省教育厅高等学校科学研究一般项目(No.L2014300)
