Objective      To determine the role of systematic heme oxygenase 1 (HO-1) in the regulation of oxidative stress and inflammation in aged skeletal muscle after intraperitoneal injection of cobalt protoporphyrin (CoPP).       Methods      Normal a

dult (2 months old) and aged (18 months old) male C57BL/6 mice were randomly divided into control group and injection group. The mice of the injection group were intraperitoneally injected with CoPP solution [5 mg/(kg·d)

]

for 3 consecutive days

and those of the control group were given normal saline at the same volume. Fresh gastrocnemius samples were harvested in 3

7 and 14 d after injection. The expression of HO-1 was examined with Western blotting. The levels of oxidative stress markers

malondialdehyde (MDA) and hydrogen peroxide (H

2

O

2

)

and the activity of antioxidant enzyme CuZn-super oxide dismutase (SOD) was detected by ELISA. Then gastrocnemius injury model was established in aged male C57BL/6 mice

and the mice were randomly divided into CoPP treatment and control group. The gastrocnemius was harvested in 3

7 and 14 d after final injection for neutrophil counting and M2 macrophage infiltration.       Results       The expression of HO-1 was higher in the aged group than the adult group

but the increase of HO-1 induced by CoPP injection was much lesser in the aged mice than adult group (P0.05). After induction of HO-1

the contents of MDA and H

2

O

2

were declined while the activities of SOD

CuZn-SOD

GSH-Px and CAT enzyme were enhanced in both adult and aged groups

whereas the level of oxidation markers were higher and the antioxidant enzyme activity was lower in aged than in adult CoPP group (P0.05). CoPP injection resulted in lower neutrophil infiltration than in the control group in 3 and 7 d after muscle injury. The CD163

+

M2 macrophage was infiltrated later

and more macrophage infiltrated in CoPP group than in the control.       Conclusion      Aged skeletal muscle has markedly lower reactivity to CoPP

and reduced ability to resist oxidative stress. Induction of HO-1 by Copp reduces early neutrophils and promotes M2 macrophage infiltration after injury

which may be helpful in skeletal muscle regeneration.