ABSTRACT
Background TLR-4 is a natural immunity receptors in immunity,and it plays an important role in the repair of central nervous system damage.But its effect in glaucoma optic nerve injury is unclear.Objective This study was to investigate the expression of TLR-4 in retina with high intraocular pressure(IOP)in genetic and Drotein level and therefore explore the mechanism of TLR-4 on retinal ganglion cells(RGCs)injury. Methods Chronic ocular hypertension models were established in the right eyes of 150 clean purebred Sprague-Dawley rats by cauterizing the 3 sallow sclera veins.IOP was measured before and after 2 h,1 day,3,7,14,28,56 days after operation by PEN Ⅱ TONO-type pen tonometer.The expression of TLR-4 protein in rat retina was detected by immunohistochemistry and Western blot,and expression of TLR-4 mRNA was assayed by real time-PCR.This experimental procedure foliowed the Statement of Association for Research in Vision and Ophthalmology. Results The IOP was elevated in various time points after operation in experimental group,showing significant differences in comparison with control group(P<0.01).The immunohistochemistry revealed that the expression of TLR-4 protein in rat retina with chronic hypertension in 2 h,1 day,3,7,14,28,56 days after operation with the high A298 values in comparison with control eyes(P<0.05-0.01).Increased levels of TLR-4 mRNA in rat retinas were detected by RTPCR in high IOP eyes compared with control eyes in all time points after operation,presenting statistically significant differences between two groups(P<0.05-0.01).Western blot detection displayed the high expression of TLR-4 in retina in high IOP eyes early after operation with statistically significant results between model group and control group (P<0.05-0. 01). Conclusion TLR-4 is up-regulated in rat retina with chronic high IOP,suggesting that TLR-4 plays an immunoregulatory effect in glaucomatous eye.
ABSTRACT
<p><b>BACKGROUND</b>Previous reports have confirmed that edaravone has protective effects against ischemia-reperfusion (IR) injury of many organs. In this study, we investigated the effect of edaravone on preventing IR injury of the lung in a canine lung transplantation model.</p><p><b>METHODS</b>Twelve weight-matched pairs of random-bred dogs were randomized into two groups. Within each pair, one dog served as donor and the other as recipient. In the study group, prostaglandin E1(PGE1)(8 microg/kg) was injected into the donor pulmonary artery (PA) before occlusion and the donor lungs were flushed with 1.0 L of LPD solution containing edaravone (10 mg/kg) and stored in the same LPD solution at a temperature of 1 degrees C for 8 hours. The left single lung transplantation was then performed and recipients received intravenous injection with edaravone (10 mg/kg) at the onset of reperfusion. In the control group, edaravone was substituted by the same volume of sterile saline solution. Another six dogs were obtained as normal control group in which left lungs were dissected after thoracotomy without an IR injury. One hour after reperfusion, or after dissection of the left lung, the right lung was excluded from perfusion and ventilation after which, cardiopulmonary parameters were measured. Wet/dry ratios, malondialdehyde (MDA) and myeloperoxidase (MPO) levels were assessed and histological analysis of lung tissue performed at the same time.</p><p><b>RESULTS</b>All animals survived until the end of the experiment. The study group showed significantly decreased wet/dry ratios (treated: (74.1 +/- 4.2)% vs control: (86.8 +/- 5.2)%, P < 0.01), MDA levels (treated: 0.50 +/- 0.08 vs. control: 0.88 +/- 0.15, P < 0.01) and MPO activity (treated: 0.23 +/- 0.05 vs. control: 0.43 +/- 0.07, P < 0.01) compared to the control group two hours after occlusion of the right side. In the control group, pulmonary vascular resistance (PVR) was increased markedly and arterial oxygen partial pressure deteriorated significantly after exclusion of the right side compared to those in the treatment group.</p><p><b>CONCLUSIONS</b>Edaravone attenuates IR-induced lung injury and preserves lung function by inhibiting oxidative stress and decreasing leukocyte extravasation in a canine lung transplantation model.</p>