Effects of L-arginine on lipopolysaccharides-induced acute lung injury by inhibiting apoptotic pathway
10.3867/j.issn.1000-3002.2009.06.001
- VernacularTitle:L-精氨酸通过抑制凋亡途径对脂多糖导致的急性肺损伤的作用
- Author:
Liping LI
;
Jianxin ZHANG
;
Lanfang LI
- Publication Type:Journal Article
- Keywords:
arginine;
apoptosis;
respiration disorders
- From:
Chinese Journal of Pharmacology and Toxicology
2009;23(6):417-422
- CountryChina
- Language:Chinese
-
Abstract:
AIM To investigate the effect and mechanism of L-arginine(L-Arg) on lipopolysaccharides(LPS)-induced acute lung injury (ALI). METHODS Models of ALI were established by injection (iv) with LPS 5 mg·kg~(-1) in male SD rats. The rats were randomly divided into 3 groups: ① saline group; ② LPS group; ③ L-Arg group. The rats in each group were further divided into 2 subgroups according to L-Arg- supplemented time: 1 h+3 h group and 6 h+3 h group. L-Arg 500 mg·kg~(-1) or saline (saline and LPS groups) was administrated at 1 or 6 h after LPS injection, respectively. The treatment lasted for 3 h, and the rats were sacrificed at 4 or 9 h after LPS injection. Apoptotic rate, caspase 3, and Bcl-2 and Bax were evaluated by flow cytometry, Western blot analysis and immunohistochemistry, respectively; meanwhile, the pathological changes of lung tissue were observed by electron microscope. RESULTS Compared with saline group, apoptosis of pulmonary cells and caspase 3 expression were significantly increased, Bcl-2 was decreased, while Bax was elevated in alveolar and airway epithelial cells in LPS group. Compared with LPS 1 h+3 h group, L-Arg 1 h+3 h decreased apoptotic pulmonary cells〔(23.8±2.8)% vs (15.4±2.3)%〕; moreover, expressions of caspase 3 (0.80±0.06 vs 0.67±0.10) and Bax (0.115±0.012 vs 0.091±0.014) were significantly decreased, while expression of Bcl-2 (0.067±0.011 vs 0.075±0.009) and Bcl-2/Bax ratio (0.586±0.114 vs 0.833±0.142) in alveolar and airway epithelial cells were markedly increased, and lung damage was alleviated. L-Arg 6 h+3 h also reduced apoptotic pulmonary cells and caspase 3 expression compared with LPS group, but the lung injury relieved slightly. CONCLUSION Relatively early administration of L-Arg can protect lungs from LPS-induced injury through inhibiting cell apoptosis, as well as increasing the expression of anti-apoptotic protein Bcl-2 and decreasing the expression of proapoptotic protein Bax and caspase 3.
