Changes of oxidative stress reaction and antagonistic action of fructose-1, 6-diphosphate in acute lung injury

Jianxin WANG; Qingliang XUE; Hong JIANG

ABSTRACT

BACKGROUND:

Fructose-1, 6-diphosphate (FDP) is an intermediate product in the course of cellular glycometabolism, and has many biological effects, such as improving cellular energy metabolism, stabilizing biological membrane, inhibiting inflammation intermedium release, antagonizing oxidation, and so on.

OBJECTIVE:

To observe the changes of oxidative stress reaction in the course of endotoxin (ET) induced acute lung injury (ALI) in flap-eared white rabbits and the antagonistic action of FDP, and to explore the therapeutic effects of FDP on ALI.

DESIGN:

Complete randomized group design, controlled experiment.

SETTING:

Department of Respiratory Medicine, General Hospital of Chinese PLA. MATERIALS The experiment was conducted in the laboratory of Department of Respiratory Medicine, General Hospital of Chinese PLA between May and December 2003. Twenty-four cleaning male flap-eared white rabbits were selected and randomly assigned into control group, injured group and interventional group with 8 animals in each group.

METHODS:

①Control group The rabbits were injected with saline (2 mL/kg) through vein. Injured group The rabbits were injected with ET (500 μg/kg) solution dissolved in 2 mL saline through cannulation in cervical vein once within 5 minutes, and then saline was injected once (Total amount of the solution was 2 mL/kg). Interventional group The rabbits were injected with the same amounts of ET solution within 5 minutes as that in the injured group, but FDP (300 mg/kg) solution was injected later (Total amount of solution was also 2 ml/kg). ②Peripheral blood and arterial blood were collected at 0, 0.5, 2, 4 and 6 hours in each group. Peripheral blood cell count and arterial blood gas were measured with autoblood cell analyzer and blood gas analyzer, respectively. After rabbits were sacrificed through bloodletting at the 6th hour, content of lipid peroxide (LPO) and activity of superoxide dismutase (SOD) in the pulmonary tissues of rabbits were measured with barbituric acid colorimetry and pyrogallol auto-oxidizing suppression, respectively. In addition, some right lower lobes of pulmonary tissues were observed on pathology with transmission electron microscope (TEM). ③Data accorded with normal distribution and homogeneity of variance were compared by t-test, or by rank sum test.MAIN OUTCOME

MEASURES:

① Comparison of result of arterial blood gas and blood cell count measured before experiment, after 0.5, 2, 4 and 6 hours experiment in rabbits of each group. ②Rabbits were sacrificed after 6 hours experiment, the pulmonary contents of LPO and the activities of SOD were measured, and the pathologic changes were also examined.

RESULTS:

①At 0.5 hour after ET injected, arterial blood oxygen pressure and white blood cell count in peripheral blood were lower significantly in the rabbits of the injured group as compared with those of the control group (t=-4.27, P ＜ 0.01,z=2.64, P ＜ 0.01 ). Arterial blood oxygen pressure and white blood cell count in peripheral blood in the interventional group showed insignificant difference as compared with the control group (P ＞ 0.05). The arterial blood oxygen pressure in the interventional group was obviously higher than that in the injured group (t=4.32,P ＜ 0.01 ). ②At the 4th hour after experiment, the arterial blood oxygen pressure in the interventional group was distinctly higher than those of the control group and the injured group (t=4.98, 2.40, P ＜ 0.01, 0.05). The white blood cell count in the injured group was dramatically less than those of the control group (z=2.42,P ＜ 0.05). ③At the 6th hours after experiment, the arterial blood oxygen pressure in the interventional group was markedly higher than those of the control group (t=3.39,P ＜ 0.01), The white blood cell count in the injured group was remarkably less than those of the control group (z=2.16,P ＜ 0.05). Content of pulmonary LPO in the injured group was significantly higher than that in the control group (t=3.70,P ＜ 0.01)while the activity of SOD was obviously lower than that in the control group(t=-4.12,P<0.01).Markedly pathological lesion appeared in the pulmonary tissue. Six hours later, the content of pulmonary LPO and the activity of pulmonary SOD in the interventional group had no remarkable difference from those in the control group (P ＞ 0.05), and the pulmonary pathologic injury showed less obvious.

CONCLUSION:

The relative deficiency of oxidative stress reaction can aggravate oxidative injury, which is an important role in pathogenesis of ET-induced ALI. FDP can improve abilities of oxidative stress reaction, inhibit oxidative injury and protect rabbits from ET-induced ALI in flapeared rabbits to a certain extent.