The protective effects of WIN55212-2 for lung injury in paraquat poisoned mice
10.3760/cma.j.issn.1671-0282.2018.11.005
- VernacularTitle:WIN55212-2对百草枯中毒小鼠肺损伤的保护作用
- Author:
Jian GUO
1
;
Xiaoye LU
;
Hongchao ZHU
;
Qian YANG
;
Changqing ZHU
Author Information
1. 上海交通大学医学院附属仁济医院急诊科
- Keywords:
Paraquat;
Mice model;
WIN55212-2;
Cannabis receptor agonist;
Acute lung injury;
Chronic lung fibrosis
- From:
Chinese Journal of Emergency Medicine
2018;27(11):1205-1210
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the protective effects of cannabinoid analogues WIN55212-2 on paraquat poisoned mice. Methods Totally 35 healthy male C57BL/6 mice were randomly(random number) divided into four groups: PQ group (paraquat poisoned, n=10), WIN 1 mg group (PQ+WIN55212-21 mg n=10), WIN 2 mg group (PQ+WIN55212-22 mg, n=10), control group (n=5).The PQ poisoned animal models were established in the PQ group, WIN 1 mg group and WIN 2 mg group by intraperitoneally injection of paraquat with a concentration of 20 mg/kg. Intraperitoneal injection of WIN55212-2 (containing Tween 80 cosolvent) at the concentration of 1 mg/kg and 2 mg/kg was performed 1 h before PQ exposure in the two interfered groups. Equivalent volume of saline was given to the control group. WIN55212-2 was injected twice a week from the second week. In the acute phase (14 d), 5 mice were randomly sacrificed in the PQ group, WIN 1 mg group and WIN 2 mg group, and 3 mice were sacrificed in the control group to obtain blood sample, bronchoalveolar lavage fluid (BALF) and lung tissue. All the remaining mice were executed on day 28, and the tissue samples were collected as mentioned above. HE staining and Masson staining were performed to observe the changes of lung tissues after PQ poisoning. Changes of TNF-α, IL-6 and TGF-β in plasma and BALF were measured by ELISA. Results In the acute phase, the pathological sections of lung tissues in the PQ group, WIN 1 mg group and WIN 2 mg group showed diffuse inflammation, which was improved after the intervention of WIN5522-2, especially in the WIN 1 mg group. IL-6 levels of BALF in the PQ group, WIN 1 mg group, WIN 2 mg group and the control group were (1024.77±124.74)U/L, (620.48±99.76)U/L, (823.29±157.88) U/L, and (180.42±20.22)U/L, respectively. IL-6 levels in the WIN 1 mg group and the WIN 2 mg group were statistically lower than those in the PQ group (P=0.021, P=0.016). However, no difference was found between the two intervention groups(P=0.114). The similar condition was also found in TNF-α in BALF and plasma. In the chronic phase, mice in the PQ group, WIN 1 mg group and WIN 2 mg group showed fibrosis in tissue by HE and Masson staining, and the inflammatory condition was improved after the intervention of WIN5522-2, which was more obvious in the WIN 1 mg group. In BALF, TNF-α level was (321.64±50.54)U/L, (260.23±48.19)U/L, (278.89±29.40)U/L, (89.76 ± 10.87)U/L in the PQ group, WIN 1 mg group, WIN 2 mg group and the control group. Differences were found between the WIN 1 mg group and the control group and the WIN 2 mg group. Similar differences were also observed in plasma TNF-α, but not in TGF-β. Conclusions A small dose of WIN55212-2 can improve the general condition of PQ poisoning mice, and reduce the inflammatory and fibrosis-related cytokines levels in PQ poisoning mice.
