[Protective effect of methylprednisolone and Naloxone on pulmonary ischemia/reperfusion injury in rats].
OBJECTIVE
To investigate the effect of methylprednisolone (MP) and naloxone (Na) on pulmonary ischemia/reperfusion (I/R) injury in rats and to study its possible mechanism.


METHODS
Seventy male Sprague-Dawley (SD) rats were used for reproduction of unilateral lung ischemia/reperfusion (I/R) injury, and they were randomly divided into five groups (14 rats in each group): sham operation group (sham group), I/R group, MP group,Na group, and MP+Na group. Each group was subdivided into two subgroups of 3-hour and 6-hour postinjury. I/R injury was produced by 45 minutes of cross-clamping of the pulmonary artery, followed by 3 hours or 6 hours of reperfusion. Apoptosis rate in lung tissue was assessed by the use of Annexin-V-PI with flow cytometry. Expression of I Kappa B-alpha and caspase-3 in lung tissue were observed by immunohistochemical stain and image analysis. The wet to dry weight (W/D) ratio, the pathological and ultrastructure changes in lung tissue were observed.


RESULTS
(1) The expression of I Kappa B-alpha in lung was obviously lower in I/R group than in 6-hour MP group (P<0.01), while expression of caspase-3 in lung tissue was significantly less intense in 3-hour and 6-hour Na group compared with I/R group (both P<0.05). Apoptosis rate in lung tissue was obviously lower in MP and 3-hour and 6-hour Na group than in I/R group (both P<0.01). The pathological and ultrastructure changes in lung tissue were less intensive. (2) Apoptosis rate, caspase-3 of lung tissue were significantly lower in MP+Na group than of 6-hour in MP, Na, I/R groups (P<0.05 or P<0.01) while the expression of I Kappa B-alpha was higher than of 6-hour Na group. The pathological and ultrastructure change in lung tissue were less more mark in MP+Na group than in other groups.


CONCLUSIONS
MP and Na inhibit apoptosis in lung I/R injury by either decreasing the activation of I Kappa B-alpha or caspase-3.MP and Na when used together in early period of lung I/R injury could exert more effective protection to lung tissue.
Zhang
Zheng
Z
Emergency Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210006, Jiangsu, China.
Qin
Hai-Dong
HD
Xu
Ying
Y
Wu
Hai-Rong
HR
Cheng
Hui
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D020672:I-kappa B Proteins / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D000072000:NF-KappaB Inhibitor alpha; D009270:Naloxone / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D020672:I-kappa B Proteins; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha; D009270:Naloxone; D053148:Caspase 3; D008775:Methylprednisolone