依托咪酯增强成年大鼠视网膜神经节细胞的轴突再生：蛋白激酶 C 的参与。

Enhancement of axonal regeneration of retinal ganglion cells in adult rats by etomidate: involvement of protein kinase C.

机构信息

Department of Neurosurgery, Wuhan General Hospital of Guangzhou Command, PLA, Wuhan, China.

出版信息

Invest Ophthalmol Vis Sci. 2011 Oct 11;52(11):8117-22. doi: 10.1167/iovs.11-7774.

DOI:10.1167/iovs.11-7774

PMID:21896870

Abstract

PURPOSE

To investigate the effect of etomidate (ET) on axonal regeneration of retinal ganglion cells (RGCs) in adult rats.

METHODS

The optic nerve was transected intraorbitally at 1 mm from the optic disc, and an autologous peripheral nerve was transplanted onto the ocular ON stump in adult rats. Then the animals were treated with ET, Gö6976, ET combined with Gö6976, phorbol-12-myristate-13-acetate (PMA), or ET combined with PMA. Four weeks after grafting, the number of regenerating RGCs labeled retrogradely with neuronal retrograde tracer was counted in all animals, and the activity of membrane protein kinase C (mPKC) and cytoplasmic PKC (cPKC) was measured in ET-treated animals.

RESULTS

The number of regenerating RGCs significantly increased when the dose of ET was increased from 2 mg/kg to 6 mg/kg, whereas the ratio of mPKC activity to cPKC activity significantly decreased in ET-treated animals. Gö6976, a potent conventional PKC inhibitor, also significantly increased the number of regenerating RGCs. However, the number of regenerating RGCs in animals treated with Gö6976 alone was significantly lower than in those treated with ET at 6 mg/kg. Combined treatment with ET at 6 mg/kg and Gö6976 did not increase the number of regenerating RGCs. In contrast, PMA, a potent PKC activator, partially abolished the positive effect of ET on the axonal regeneration of axotomized RGCs.

CONCLUSIONS

These results suggest that ET promotes axonal regeneration of RGCs in adult rats, in part by inhibiting conventional PKC.

摘要

目的

研究依托咪酯（ET）对成年大鼠视网膜神经节细胞（RGC）轴突再生的影响。

方法

在距视盘 1mm 的眶内切断视神经，将自体周围神经移植到成年大鼠眼 ON 残端。然后，用 ET、Gö6976、ET 联合 Gö6976、佛波醇-12-肉豆蔻酸-13-乙酸酯（PMA）或 ET 联合 PMA 处理动物。移植后 4 周，用神经元逆行示踪剂逆行标记所有动物再生的 RGC 数量，并测量 ET 处理动物膜蛋白激酶 C（mPKC）和胞质蛋白激酶 C（cPKC）的活性。

结果

当 ET 剂量从 2mg/kg 增加到 6mg/kg 时，再生 RGC 的数量显著增加，而 ET 处理动物的 mPKC 活性与 cPKC 活性的比值显著降低。Gö6976，一种有效的常规 PKC 抑制剂，也显著增加了再生 RGC 的数量。然而，单独用 Gö6976 处理的动物中再生 RGC 的数量明显低于用 6mg/kg ET 处理的动物。用 6mg/kg ET 和 Gö6976 联合治疗并不能增加再生 RGC 的数量。相反，PKC 激活剂 PMA 部分削弱了 ET 对轴突切断的 RGC 轴突再生的正向作用。