Yonsei Med J.  2008 Feb;49(1):144-150.

Intratracheal Administration of Endotoxin Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats

• Shim JW
• Chang YS
• Park WS

Abstract

PURPOSE
This study was undertaken to determine the effects of intratracheal administration of endotoxin on hyperoxia-induced lung injury in neonatal rats. MATERIALS AND METHODS: Newborn Sprague Dawley rat pups were divided into four experimental groups: normoxia control (NC), normoxia with endotoxin treatment (NE), hyperoxia control (HC), and hyperoxia with endotoxin treatment (HE) groups. In HC and HE, rat pups were subjected to 14 days of hyperoxia (> 95% oxygen) within 12 hours after birth. In endotoxin treated group (NE and HE), Escherichia coli endotoxin (0.5microgram in 0.03mL of saline) was given intratracheally at the 1st, 3rd and 5th postnatal day. Radial alveolar count (RAC), mean linear intercept (MLI), RAC/MLI ratios, and degree of fibrosis were measured to assess the changes in lung morphology. RESULTS: During the research period, survival rates in both HC and HE were notably reduced 7 days after endotoxin was administered, but body weight gain was considerably reduced only in HC. On day 14, significant arrest in alveolarization, as evidenced by the decrease of RAC and RAC/MLI ratio and increase of MLI as well as increased fibrosis, were noted in HC. Although slight but significant arrest in alveolarization and increased fibrosis score were observed in NE compared to NC, the hyperoxia-induced lung damage observed in HC was significantly improved in HE. CONCLUSION: This study suggests that intratracheal administration of endotoxin significantly attenuated hyperoxia-induced lung injury in neonatal rats.

Keyword

Bronchopulmonary dysplasia; endotoxin; hyperoxia

MeSH Terms

Animals
Animals, Newborn
Body Weight
Drug Administration Routes
Endotoxins/*administration & dosage
Hyperoxia/*complications
Lung Diseases/*chemically induced/*etiology/pathology
*Lung Injury
Rats
Rats, Sprague-Dawley

Figure

• 

  Fig. 1 Time course of survival in each experimental group in 95% oxygen or room air for 14 days. Normoxia control group (NC), normoxia with endotoxin treatment group (NE), hyperoxia control group (HC), hyperoxia with endotoxin treatment group (HE). Values represent group means±SD. *p < 0.05 vs NC.

• 

  Fig. 2 Time course of weight change of endotoxin instillation and control group rat pups in > 95% oxygen or room air for 14 days. Normoxia control group (NC), normoxia with endotoxin treatment group (NE), hyperoxia control group (HC), hyperoxia with endotoxin treatment group (HE). Values represent group means±SD. *p < 0.05 vs NC.

• 

  Fig. 3 Representative light micrographs of lung of rat pups at postnatal day 14. (A) Lung structure of neonatal rats in normoxia at day 14 (NC). Note prominent secondary alveolar septa formation. (B) Intratracheal instillation of endotoxin (NE) shows less prominent secondary alveolar septa formation and slightly alveolar dilatation. (C) Hyperoxia causes distal air space enlargement, and alveolar architecture is simplified (HC) and prominent fibrosis. (D) Intratracheal instillation of endotoxin during hyperoxia (HE), significantly attenuated hyperoxia-induced lung injury (Hematoxylin-eosin stain, original magnification ×100).

• 

  Fig. 4 Radial alveolar counts (A), mean linear intercepts (B), and radial alveolar counts/mean linear intercepts ratio (C) at postnatal day 14 in four treatment groups: normoxia control group (NC), normoxia with endotoxin treatment group (NE), hyperoxia control group (HC), hyperoxia with endotoxin treatment group (HE). Columns are means±SD. *p < 0.05 vs NC, †p < 0.05 vs NE, ‡p < 0.05 vs HC.

• 

  Fig. 5 Effect of hyperoxia and endotoxin on fibrosis at post-natal day 14 rat lung. Top: representative photomicrographs (×400 magnification) for each condition. Bottom: mean fibrosis scores of each group; normoxia control group (NC), normoxia with endotoxin treatment group (NE), hyperoxia control group (HC), hyperoxia with endotoxin treatment group (HE). Values represent group means±SD. *p < 0.05 vs NC; †p < 0.05 vs NE; ‡p < 0.05 vs HC.

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