| The problem of respiratory and infection are the main contents of neonatal management and the hotspot in the field of newborn in recently years. Respiratory is the primary problem in neonatal intensive care unit, and hypoxia is one of the common manifestation in neonates, it can endanger the lives of severe infants. Oxygen therapy is one of the common method used to treat hypoxia disease. As one means of improving the pulmonary function, mechanical ventilation is the most used and effective method.But oxygen is a double-edged sword, blood oxygen concentration would inevitably fluctuate in the process of oxygen therapy. The high volume fraction oxygen (high oxygen) disease have caused more and more the people’s attention in recently years. Broncho-pulmonary dysplasia, lung injury, retinopathy caused by normobaric hyperoxia have been confirmed in animal experiment and clinical research. Recently it has been found that normobaric hyperoxia can affect the development of neonatal immature brain, cause nerve cells apoptosis and cerebral white matter damage. Infectious disease is one of the important infants diseases and the main cause of neonatal death.Neonates, especially for premature infants, for the immature immune system and low resistance, are prone to infectious diseases. With the deepening understanding of infectious diseases and improvement of preventive measures, although the disease has a decline trend year by year, but the incidence and mortality of neonates infectious diseases are still the first at present in China. Domestic and international animal experiments and clinical studies have showed that infection and inflammation can lead to neonatal brain injury. Clinical cases with high oxygen and infection coexist are not rare, for example serious infection,pneumonia, neonatal sepsis combined respiratory failure, need to respiratory support. So infection and high oxygen problems aroused our interest.PurposeDomestic and international researchs show that infection and high oxygen can both lead to neonatal brain damage, but the current studies about the combined effect of neonatal brain damage are less.We aim to investigate the effects of normobaric hyperoxia and/or lipopolysaccharide (LPS) on neonatal rat brain development and possible mechanisms in this paper.Materials and Methods120postnatal day2(P2) SD rats were randomly assigned into4groups:LPS group, hyperoxia group, LPS+hyperoxia group, control group. General condition and body weight of each group were observed and recorded every day. LPS group administration of intraperitoneal injection LPS (0.6mg-Kg-1) daily, maintain oxygen volume fraction21%in the same indoor air to P7; High oxygen group were placed together with their mother in oxygen box, intraperitoneal injection the same volume of physiological saline (9g·L-1) every day, and maintain the oxygen volume fraction at (80±2)%to P7; LPS+high oxygen group intraperitoneal injection of LPS (0.6mg-Kg-1) every day, and maintain the oxygen volume fraction at (80±2)%untilP7; Control group were administrated the same volume of physiological saline (9g·L-1) by intraperitoneal injection every day, and maintain oxygen volume fraction21%to P7.10rats of each group were taked out when bred to P7, perfused the brain, fixed and paraffined. The expression of active Caspase-3and nuclear factor-KappaB P65in the brain were detected by immunohistochemistry staining. The level of interleukin-6and8-iso-Prostaglandin F2a in the brain homogenate were measured by ELISA after brain tissue homogenate for another 10in each group. The expression of myelin basic protein in the brain was detected by immunohistochemistry staining on P12for each remaining10rats.Results1. The expression of Caspase-3and NF-kB P65of the four groups on P7had the same trends. The number of positive cells from high to low were LPS+hyperoxia group, LPS group/hyperoxia group, control group. In control group, LPS group, hyperoxia group and LPS+hyperoxia groups, Caspase-3positive cell number in brain tissue were:6.80±1.03,17.00±2.83,18.40±4.35,23.90±3.84respectively.NF-KB P65positive expression cells number were:7.71±1.34,21.20±3.77,18.90±2.23,31.90±4.91respectively.Significant difference were found between the control group and the other three groups (P<0.05). There was also significant difference between LPS+hyperoxia group and LPS group or hyperoxia group (F=47.61,87.46, P<0.05).2. The average integral optical density value of MBP in the brain on P12in control group,hyperoxia group, LPS group, LPS+hyperoxia group were:139.10±8.28,127.69±7.23,123.09±8.17,110.30±8.14.Compared with control group, the expression of MBP in LPS group is low, the difference was statistically significant (P <0.05).Although the expression of MBP in hyperoxia group is high than control group, but no statistically significant difference was found(P>0.05); the expression of MBP in LPS+hyperoxia group reduced obviously compared with LPS group, the statistically significant difference were found between the two groups (F=27.29, P<0.05).3. The level of IL-6in the brain from high to low order is LPS+hyperoxia group, LPS group, hyperoxia group and control group.The expression level were:285.01±24.96,230.84±34.98,165.52±31.76,154.36±21.75(ng·g-1)respectively.Comparedwith control group,the expression level of IL-6in LPS group is high, the difference was statistically significant (P<0.05);. Although the expression level of IL-6in hyperoxia group is higher than that of control group, but no statistically significant difference was found(P>0.05).The expression level of IL-6in LPS+hyperoxia group rised obviously compared with LPS group, the statistically significant difference were found between the two groups (F=44.59, P<0.05).4.The level of8-iso-PGF2a in the brain of LPS+hyperoxia group, hyperoxia group, LPS group and control group were302.75±32.12,225.59±26.89,162.78±31.35,143.63±19.81(ng·g-1) respectively.Compared with control group, the expression level of8-iso-PGF2a in hyperoxia group is high, the difference was statistically significant (P<0.05).Although the expression level of8-iso-PGF2a in LPS group is higher than that of control group, but no statistically significant difference was found(p>0.05).The expression level of8-iso-PGF2a in LPS+hyperoxia group rised obviously compared with hyperoxia group, the statistically significant difference were found between the two groups (F=66.49, P<0.05).Conclusions1. Both postnatal infection and normobaric hyperoxia may cause neuronal cell apoptosis and reduce the expression of MBP.The combination of infection and normobaric hyperoxia may aggravate the degree of neonatal rat brain damage.2. The synergy mechanisms of infection and high oxygen to brain damage are: NF-kB pathway mediated by TLR may be involved in inflammation and oxidative stress, and may mediate Caspase-3related apoptosis of neuronal cell and white matter injury. |
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