Effects of recombinant murine granulocyte macrophage-colony-stimulating factor on lung injury of hyperoxia-exposed newborn rats

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TIAN Zhao-fang(Department of Pediatrics, Huai'an First Hospital Affiliated Nanjing Medical University, Huai'an, 223300,China)
LI Yu-hong(Department of Pediatrics, Huai'an First Hospital Affiliated Nanjing Medical University, Huai'an, 223300,China)
FU Xue-mei()
FENG Zhi-chun()
Journal Title:
Volume 12, Issue 03, 2009
Key Word:
Granulocyte macrophage colony-stimulating factor, recombinant; Hyperoxia; Lung diseases; Rats

Abstract: Objective To investigate the effects of systemic treatment with recombinant murine granulocyte macrophage-colony stimulating factor (GM-CSF) on lung injury in hyperoxia-exposed newborn rats. Methods Thirty-two 3-day-old SD rats were randomly divided into four groups: hyperoxia exposed + GM-CSF group (Group 1),air-exposed+ GM-CSF group (Group 2), hyperoxia exposed group (Group 3) and air-exposed group (Group 4). The rats in Group 1 and 3 were placed in a sealed Plexiglas chamber maintaining O2 levels above 95% and those in Group 2 and 4 were exposed to air. Rats in Group 1 and 2 were injected with GM-CSF (9 μg/kg ih. ) at 24 h, 72 h and 120 h, respectively and those in Group 3 and 4 received subcutaneous injection of saline at the same time point. All rats were sacrificed 7 d later, and immunohistochemistry was used to evaluate the expression of telomerase reverse transcriptase (TERT) grade and proliferating cell nuclear antigen (PCNA) index in lung tissue; and total numbers of cells in bronchoalveolar lavage fluid (BALF) were counted and the percentages of mononuclear cells and neutrophils were calculated. The levels of TNFα and TGFβ1 of tissue homogenates were detected by ELISA. The value of radical alveolar count(RAC) was calculated. Results (1) There were significant differences in the values of RAC, total numbers of white blood cells (WBC) and the percentages of mononuclear cells and neutrophils in BALF, the levels of TNFα and TGFβ1 of tissue homogenates and PCNA index among the four groups. (2) Compared with Group 4, both PCNA index and RAC decreased (P<0.05), and the levels of TNFα and TGFβ1, WBC, mononuclear cells and neutrophil count increased in Group 3. Compared to Group 3, both PCNA index and RAC increased (P<0.05), and the levels of TNFα and TGFβ1 decreased in Group 1 (P<0. 05), but no differences was found in the WBC, mononuclear cells and neutrophil count (P>0. 05). (3) TERT grade in Group 1 was obviously increased, while there were no difference among the other groups. Conclusions The protective effect of GM-CSF on lung injury of newborn rats suffered from hyperoxia may be related to the increase of stem cells proliferation and the improvement of local microenvironment.

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