L-Carnitine effect on induced hyperlipidemia on premature rats: fertility profile.

This study was designed to investigate the effect of hypercholesterolemia on the reproductive performance of premature male rats and to evaluate the influence of L-Carnitine (CAR) in maintaining their fertility. Sixty rats were divided randomly into three groups. Control group (CG n=20 rats), cholesterol feeding group 1 (CFG1 n=20 rats) fed 1.5% cholesterol with diet for one month, and cholesterol feeding group 2 (CFG2 n=20 rats) fed 1.5% cholesterol with diet + CAR 150 mg/kg body weight (B.W.) given by water for one month. Results showed a significant increase in body weight of CFG1 compared with CG and CFG2. The lipid profile of CFG1 after one month of feeding cholesterol showed a significant increase in serum cholesterol and triglyceride compared with CG and with the group that watered by CAR and CFG2. Results of sperms parameters in CGF2 showed a significant increase in sperms count with sperms live percentage and a significant decrease in sperms abnormalities percentage compared with CGF1 and CG. The hormonal profile showed a significant decrease in serum testosterone levels in rats from CFG1 compared with CFG2 and CG. In conclusion, CAR is a powerful antioxidant that can maintain the parameters of sperms of hypercholesterolemic premature rats, which may enhance the fertilizing ability of subfertile rats that may occur due to hyperlipidemia.

Elevation of stromal cell-derived factor 1 and C-X-C chemokine receptor type 4 in white matter damage treatment with recombinant human erythropoietin and human umbilical cord mesenchymal stem cells in a rat model of preterm birth.

OBJECTIVES: To investigate the role of stromal cell-derived factor 1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR-4) in the premature brain with white matter damage (WMD) undergoing treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs) and recombinant human erythropoietin (rhEPO). EXPERIMENTAL DESIGN: Three-day-old Sprague-Dawley (SD) rats were randomly divided into sham operation group, hypoxia-ischemia (HI) group, rhEPO treated HI group, hUC-MSCs treated HI group, and rhEPO + hUC-MSCs treated HI group. WMD was established in all groups except the Sham group. SDF-1 and CXCR-4 levels in each group were detected at postnatal day (P) 5, P7, and P14. Pathological changes were assessed via HE staining at P14 and neuroethological tests were performed at P28. OBSERVATIONS AND CONCLUSIONS: The rhEPO and hUC-MSCs intervention reduced injury area, increased body weight at P7, and improved neurobehavioral scores at P28. Furthermore, their combined use proved even more beneficial. SDF-1 levels in the rhEPO group were higher than those in the other groups and highest in the hUC-MSCs + rhEPO group (all p < .01). SDF-1 levels in the hUC-MSCs + rhEPO and rhEPO groups were increased at P5 and reached a peak at P7. CXCR-4 levels in the hUC-MSCs group were higher than those in the other groups and highest in the hUC-MSCs + rhEPO group (all p < .01). CXCR-4 levels were also increased at P5 and highest at P14. SIGNIFICANCE: hUC-MSCs + rhEPO might reduce nerve cell damage and improve neurobehavioral development, in connection with increased SDF-1 and CXCR-4 expression, in premature rats with WMD due to hypoxic-ischemic injury.

Postnatal high-protein diet improves learning and memory in premature rats via activation of mTOR signaling.

PURPOSE: The present study investigated whether a high-protein diet affects spatial learning and memory in premature rats via modulation of mammalian target of rapamycin (mTOR) signaling. METHODS: Pre- and full-term Sprague-Dawley pups were fed a normal (18% protein) or high-protein (30% protein) diet (HPD) for 6 or 8 weeks after weaning. Spatial learning and memory were tested in the Morris water maze at week 6 and 8. The activation of mTOR signaling pathway components was evaluated by western blotting. RESULTS: Spatial memory performance of premature rats consuming a normal and HPD was lower than that of full-term rats on the same diet at 6 weeks, and was associated with lower levels of ribosomal protein S6 kinase p70 subtype (p70S6K) and initiation factor 4E-binding protein 1 (4EBP1) phosphorylation in the hippocampus. Spatial memory was improved in 8-week-old premature rats on an HPD as compared to those on a normal diet. Premature rats on an HPD had p70S6K and 4EBP1 phosphorylation levels in the hippocampus that were comparable to those of full-term rats on an HPD. CONCLUSION: Long-term consumption of a protein-rich diet can restore the impairment in learning and memory in pre-term rats via upregulation of mTOR/p70S6K signaling.

Effects of Hyperoxia on Cytoplasmic Thioredoxin System in Alveolar Type Epithelial Cells of Premature Rats / 华中科技大学学报（医学）（英德文版）

This study investigated the effects of hyperoxia on dynamic changes of thioredoxin-1 (Trx1)and thioredoxin reductase-1 (TrxR1) in alveolar type Ⅱ epithelial cells (AECⅡ) of premature rats.Pregnant Sprague-Dawley rats were sacrificed on day 19 of gestation.AEC Ⅱ were isolated and purified from the lungs of premature rats.When cultured to 80％ confluence,in vitro cells were randomly divided into air group and hyperoxia group.Cells in the hyperoxia group were continuously exposed to 95％ O2/5％ CO2 and those in the air group to 95％ air/5％ CO2.After 12,24 and 48 h,cells in the two groups were harvested to detect their reactive oxygen species (ROS),apoptosis,TrxR1 activity and the expressions of Trx1 and TrxR1 by corresponding protocols,respectively.The results showed that AEC Ⅱ exposed to hyperoxia generated excessive ROS and the apoptosis percentage in the hyperoxia group was increased significantly at each time points as compared with that in the air group (P＜0.001).Moreover,TrxR1 activity was found to be markedly depressed in the hyperoxia group in comparison to that in the air group (P＜0.001).RT-PCR showed the expressions of both Trx1 and TrxR1 mRNA were significantly increased in AEC Ⅱ exposed to hyperoxia for 12 and 24 h (P＜0.01),respectively.At 48 h,the level of Trx1 mRNA as well as that of TrxR1 mRNA in the hyperoxia group was reduced and showed no significant difference from that in the air group (P＞0.05).Western blotting showed the changes of Trx 1 protein expressions in the hyperoxia group paralleled those of Trx1 mRNA expressions revealed by RT-PCR.It was concluded that hyperoxia can up-regulate the protective Trx1/TrxR1 expressed by AEC Ⅱ in a certain period,however,also cause dysfunction of the cytoplasmic thioredoxin system by decreasing TrxR1 activity,which may contribute to the progression of oxidative stress and cell apoptosis and finally result in lung injury.

Retinoic Aacid Diminished the Expression of MMP-2 in Hyperoxia-exposed Premature Rat Lung Fibroblasts through Regulating Mitogen-activated Protein Kinases / 华中科技大学学报（医学）（英德文版）

This study examined the effects of retinoic acid (RA),PD98059,SP600125 and SB203580 on the hyperoxia-induced expression and regulation of matrixmetalloproteinase-2 (MMP-2) and metalloproteinase-2 (TIMP-2) in premature rat lung fibroblasts (LFs).LFs were exposed to hyperoxia or room air for 12 h in the presence of RA and the kinase inhibitors PD98059 (ERK1/2),SP600125 (JNK1/2) and SB203580 (p38) respectively.The expression levels of MMP-2 and TIMP-2 mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).MMP-2 activity was measured by zymography.The amount of p-ERK1/2,REK1/2,p-JNK1/2,JNK1/2,p-p38 and p38 was determined by Western blotting.The results showed that:(1) PD98059,SP600125 and SB203580 significantly inhibited p-ERK1/2,p-JNK1/2 and p-p38 respectively in LFs; (2) The expression of MMP-2 mRNA in LFs exposed to hyperoxia was decreased after treatment with RA,SP600125 and SB203580 respectively (P＜0.01 or 0.05),but did not change after treatment with PD98059 (P＞0.05).Meanwhile,RA,PD98059,SP600125 and SB203580 had no effect on the expression of TIMP-2 mRNA in LFs exposed to room air or hyperoxia (P＞0.05); (3) The expression of pro- and active MMP-2 experienced no change after treatment with RA or SP600125 in LFs exposed to room air (P＞0.05),but decreased remarkably after hyperoxia (P＜0.01 or 0.05).SB203580 inhibited the expression of pro- and active MMP-2 either in room air or under hyperoxia (P＜0.01).PD98059 exerted no effect on the expression of pro- and active MMP-2 (P＜0.05).It was suggested that RA had a protective effect on hyperoxia-induced lung injury by down-regulating the expression of MMP-2 through decreasing the JNK and p38 activation in hyperoxia.