碳酸氢盐对新生大鼠视网膜血管系统及酸中毒诱导性视网膜病变的影响。

Effect of bicarbonate on retinal vasculature and acidosis-induced retinopathy in the neonatal rat.

作者信息

Berdahl John P, Leske David A, Fautsch Michael P, Lanier William L, Holmes Jonathan M

机构信息

Mayo Medical School, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2005 Apr;243(4):367-73. doi: 10.1007/s00417-004-0997-5. Epub 2004 Nov 19.

DOI:10.1007/s00417-004-0997-5

PMID:15558294

Abstract

BACKGROUND

Systemic acidosis induces preretinal neovascularization (NV) analogous to retinopathy of prematurity (ROP) in the neonatal rat. Sodium bicarbonate is used in human neonates to treat acidosis. The effects of alkali administration on the developing retinal vasculature and on acidosis-induced retinopathy (AIR) are unknown. We investigated the effect of sodium bicarbonate gavage on the retinal vasculature of normal and acidotic neonatal rats to determine (1) whether bicarbonate treatment is associated with preretinal NV and (2) whether AIR can be prevented with systemic bicarbonate treatment.

METHODS

The extent of acidosis and alkalosis were initially determined from carotid arterial blood samples. In the bicarbonate-alone study, newborn rats were randomized into litters of 25 and received bicarbonate doses of 15 mmol/kg twice daily and 20 mmol/kg once daily from days 2 to 7. Control animals received saline gavage. In the AIR treatment study, acidosis was induced in neonatal rats by intraperitoneal injection of acetazolamide 200 mg/kg from days 2 to 7. Acetazolamide-treated rats received either additional bicarbonate gavage or no additional treatment. Eyes were enucleated on day 13, and the retinal vasculature was assessed for NV using ADPase staining techniques and light microscopy.

RESULTS

Systemic alkalosis (peak pH 7.55+/-0.02; mean +/- SD) was confirmed with bicarbonate gavage, and partial reversal of acidosis was confirmed when acetazolamide-treated rats received bicarbonate. Surviving rats receiving bicarbonate 15 mmol/kg twice daily (28% survival) and 20 mmol/kg bicarbonate once daily (45% survival) had an incidence of preretinal NV of 9% and 8%, respectively. No NV was seen in saline-control rats. In the acetazolamide-treated rats, the incidence of preretinal NV in surviving rats was numerically lower in bicarbonate-treated rats than acetazolamide-only controls (8% versus 24%, p=0.065) but with only 19% survival in the bicarbonate-treated rats.

CONCLUSIONS

In the neonatal rat, alkalosis induced by bicarbonate gavage is associated with a low incidence of mild, preretinal NV similar to ROP. Although treating acidotic rats with bicarbonate may reduce the incidence of preretinal NV, treatment was associated with an unacceptable mortality rate.

摘要

背景

全身酸中毒可诱导新生大鼠视网膜前新生血管形成（NV），类似于早产儿视网膜病变（ROP）。碳酸氢钠用于人类新生儿治疗酸中毒。给予碱对发育中的视网膜血管系统和酸中毒诱导的视网膜病变（AIR）的影响尚不清楚。我们研究了碳酸氢钠灌胃对正常和酸中毒新生大鼠视网膜血管系统的影响，以确定（1）碳酸氢盐治疗是否与视网膜前NV有关，以及（2）全身碳酸氢盐治疗是否可以预防AIR。

方法

最初从颈动脉血样中确定酸中毒和碱中毒的程度。在单独使用碳酸氢盐的研究中，新生大鼠被随机分成每组25只的窝，从第2天至第7天每天接受两次15 mmol/kg的碳酸氢盐剂量和每天一次20 mmol/kg的剂量。对照动物接受盐水灌胃。在AIR治疗研究中，从第2天至第7天通过腹腔注射200 mg/kg乙酰唑胺诱导新生大鼠酸中毒。接受乙酰唑胺治疗的大鼠要么接受额外的碳酸氢盐灌胃，要么不接受额外治疗。在第13天摘除眼球，使用腺苷三磷酸酶（ADPase）染色技术和光学显微镜评估视网膜血管系统的NV情况。

结果

通过碳酸氢盐灌胃证实了全身碱中毒（峰值pH 7.55±0.02；平均值±标准差），并且当接受乙酰唑胺治疗的大鼠接受碳酸氢盐时证实了酸中毒的部分逆转。每天接受两次15 mmol/kg碳酸氢盐（存活率28%）和每天一次20 mmol/kg碳酸氢盐（存活率45%）的存活大鼠视网膜前NV的发生率分别为9%和8%。在盐水对照大鼠中未观察到NV。在接受乙酰唑胺治疗的大鼠中，接受碳酸氢盐治疗的存活大鼠视网膜前NV的发生率在数值上低于仅接受乙酰唑胺治疗的对照组（8%对24%，p=0.065），但接受碳酸氢盐治疗的大鼠存活率仅为19%。