依托咪酯通过PKC/NF-κB信号通路增加成年大鼠视神经损伤后RGC存活

目的　探讨依托咪酯对成年大鼠视神经损伤后视网膜神经节细胞（ｒｅｔｉｎａｌｇａｎｇｌｉｏｎｃｅｌｌ，ＲＧＣ）的保护作用及其机制。方法　应用大鼠视神经眶内段切断模型，荧光金逆行标记存活ＲＧＣ；腹腔注射依托咪酯或玻璃体内注射蛋白激酶Ｃ（ｐｒｏｔｅｉｎｋｉ-ｎａｓｅＣ，ＰＫＣ）抑制剂Ｇ６９７６干预，应用ＰｅｐＴａｇ非同位素ＰＫＣ检测试剂盒检测视网膜ＰＫＣ活性，应用免疫印迹法分析视网膜核转录因子-κＢ（ｎｕｃｌｅａｒｆａｃｔｏｒｋａｐｐａＢ，ＮＦ-κＢ）水平。结果　依托咪酯显著增加大鼠视神经损伤后７ｄＲＧＣ存活数量（Ｐ＜０．０５），而且显著降低视网膜ＰＫＣ活性和ＮＦ-κＢ水平（均为Ｐ＜０．０５）。Ｇ６９７６同样显著增加大鼠视神经损伤后７ｄＲＧＣ存活数量（Ｐ＜０．０５），联合应用依托咪酯和Ｇ６９７６，其存活ＲＧＣ数量与单纯应用依托咪酯差异无统计学意义（Ｐ＞０．０５）；Ｇ６９７６显著降低视网膜ＮＦ-κＢ水平（Ｐ＜０．０５）。结论　依托咪酯可显著增加大鼠视神经损伤后ＲＧＣ存活数量，其机制可能与抑制ＰＫＣ／ＮＦ-κＢ信号通路有关。

Etomidate promoting retinal ganglion cells survival after optic nerve transaction in adult rats via inhibition of PKC/NF-KB signaling

Objective To investigate the effects of etomidate on retinal ganglion cells ( RGC ) survival after optic nerve transaction in adult rats and its mecharusm. Methods The left optic nerves were transected at I mm from the optic disc in adult female SD rats. The rats were treated with etmidate by intraperitoneal injection , PKC inhibitor G06976 by intravenous injection. or with etomidate combined with G06976. The surviving RGC were retrogradely labeled by fluorogold and the surviving RGC were counted in the flat-mounted retinas at 7 days after optic nerve transaction. The activity of membrane protein kinase C ( mPKC) and cytoplasmic PKC ( cPKC) was measured using the PepTag non-radioactive protein kinase assay kit. The protein expression level of nuclear factor kappa B ( NF-KB) were analyzed by Western blotting. Results Etomidate significantly increased the number of surviving RGC at 7 days after optic nerve transaction in adult rats ( P < 0. 05 ) , and significantly reduced the retinal PKC activity and retinal level of NF-KB (P < 0. 05 ) . G06976 also significantly increased the number of surviving RGC (P < 0. 05 ) , etonudate combined with G06976 did not sigruficantly increase the number of surviving RGC compared with etomidate (P > 0. 05 ) . G06976 significantly reduced the retinal level of NF-KB ( P < 0. 05 ) . Conclusion Etomidate promotes RGC survival in adult rats after optic nerve transaction in part by inhibiting PKC/NF-KB signaling.