Lidocaine與Methylprednisolone對於大鼠視網膜缺血再灌流病變模式的神經保護效力

Abstract

本實驗目的為評估注射型藥物lidocaine（LDC）與methylprednisolone（MP）是否對於視網膜缺血性病變有神經保護效果。經高眼內壓誘發視網膜缺血，將SD大鼠分成三組：包括IR（ischemia-reperfusion）無治療之對照組（n=5）、給予LDC（n=7）與MP（n=7）兩組IR治療實驗組。大鼠眼前房以30號針頭穿刺並連接上含生理食鹽水的點滴袋，將眼內壓提高到130mmHg造成眼底視網膜完全缺血的狀態持續45分鐘。LDC治療實驗組在缺血前30分鐘靜脈注射lidocaine 1.5mg/kg的劑量，隨即以2mg/kg/hr的速率持續靜脈注射到缺血結束後60分鐘。MP治療實驗組給予兩次methylprednisolone 30mg/kg的靜脈注射，分別在缺血前2分鐘與缺血後馬上給予。傷害評估利用缺血後三天視網膜電波圖來檢查視網膜功能性的改變，以及缺血後七天在組織病理形態計量上視網膜的厚度改變。視網膜電波圖結果顯示a波在IR無治療組下降35.2%±22.3%， LDC組下降49.7%±21.3%，而MP組無顯著差異；b波在無治療組下降81.0%±4.6%，LDC組下降80.7%±5.1%，而MP組僅稍微下降17.6%±13.4%。組織病理結果顯示內層視網膜傷害均比外層強，而內叢狀層與外核層的比值（IPL/ONL ratio）與正常的百分比分析（% of正常），IR無治療組只剩下48.8%，LDC治療組顯示存留程度為80.1%，而MP治療組剩存的百分比可高達96.2%，幾乎沒有下降。結論為MP對於高眼壓造成的視網膜缺血性傷害確有良好的視網膜神經保護效果，包括在視網膜功能及組織病理方面；而LDC的視網膜保護效果僅表現在病理的型態計量上，在視網膜電波圖檢查並未顯示保護效果。

Purpose: To evaluate the neuroprotective effects of intravenous (IV) lidocaine (LDC) and methylprednisolone (MP) against the retinal ischemia-reperfusion (IR) insult. Methods: SD rats were divided into 3 groups, the IR control (n=5), LDC (n=7) and MP (n=7). Saline was infused into the anterior chamber using 30-gauge needle, which created a high intraocular pressure than blood pressure and lasted for 45 min. LDC bolus (1.5mg/kg) was IV injected 30 min before ischemia and then a constant rate infusion (CRI) with 2mg/kg/hr was given until 60 min after reperfusion. MP bolus (30mg/kg) was IV administered twice at 2 min before and immediately after ischemia, respectively. The damage to retinal function was evaluated by electroretinogram (ERG) 3 days after ischemia and by morphometrical histology analysis 7 days after ischemia. Results: The functional analysis of the retina by ERG revealed a 35.2% reduction of a-wave in the IR control group, 49.7% reduction in the LDC group but no significant change in the MP group. The b-wave reduction showed 81.0% in the IR control, 80.7% in the LDC group and 17.6% in the MP group. In the morphometrical histology, the retinal inner plexiform layer/outer nuclear layer (IPL/ONL) ratio was reduced following IR damage compared with that in the normal control. The IPL/ONL ratio was reduced to 48.8% in the IR control group, 80.1% in the LDC group and 96.2% in MP group. Conclusions: The MP showed significantly good neuroprotective effects on retinal IR injury, and the LDC showed moderate neuroprotective effects demonstrated in histology but not in retinal function.