洛美利嗪对膳食诱导的C57BL/6J肥胖小鼠视网膜神经节细胞凋亡的保护作用

Neuroprotective effects of lomerizine on retinal ganglion cells in the diet-induced obese C57BL /6J mice

目的:探讨洛美利嗪(LOM)对高脂饮食诱导的C57BL/6J肥胖小鼠视网膜神经节细胞(RGCs)凋亡的保护作用。方法:小鼠54只随机分为两组,高脂饲料喂养19wk,其中一组同时每天按80mg/kg给予LOM灌胃。筛选出肥胖组(DIO)和肥胖+洛美利嗪组(DIO+LOM),对照组(CON)小鼠给予基础饲料。至第19wk末,应用透射电镜观察各组小鼠RGCs的超微结构改变,采用TUNEL法检测各组小鼠RGCs的凋亡情况,并应用激光共聚焦显微镜检测RGCs内钙离子的浓度。结果:透射电镜结果显示,与CON组比较,DIO组小鼠RGCs体积变小,细胞质分布紊乱,核染色质发生固缩,而DIO+LOM组小鼠RGCs的形态学改变较DIO组明显减轻。TUNEL法检测结果显示,与CON组比较,DIO组小鼠GCL层可见较多的凋亡细胞,其细胞凋亡率显著升高(P<0.01),DIO+LOM组RGCs的凋亡率与DIO组比较显著降低(P<0.05)。激光共聚焦结果显示,与CON组比较,DIO组小鼠RGCs内Ca2+荧光染色明显增强,其荧光染色强度比值显著升高(P<0.01),而DIO+LOM组RGCs内Ca2+荧光染色强度较DIO组有明显下降(P<0.01)。结论:洛美利嗪对肥胖引起的RGCs的损伤和凋亡具有保护作用,其机制可能与减轻细胞内Ca2+超载有关。

AIM： To research the neuroprotective effects of lomerizine （ LOM ） on retinal gangli on cells （ RGCs ） in the diet-induced obeseC57BL/6J mice. METHODS：Fifty-four mice were randomly divided into two groups which were fed a high-fat diet for 19wk.One group mice were lavaged LOM by the dosage of 80mg/kg daily at the same time.The obese mice were selected and divided into diet-induced obesity （ DIO） group, diet-induced obesity and lomerizine （DIO＋LOM） group.The mice in the control （ CON） groupw ere fed abasal diet. The ultrastructural changes of RGCs were detected by transmission electron microscope.The cellular apoptosis was detected by TUNEL. The laser scanning confocal microscope was used to measure intracellular calcium ion concentration. RESULTS：Compared with the CON group , the RGCs in DIO group showed smaller and condensation of nuclear chromatin and increased electron density of the cytoplasm, whereas the changes in DIO＋LOM mice were obviously diminished.TUNEL staining showed that the number of apoptosis cells in the ganglion cell layer （ GCL ） increased in DIO group and the percentage of apoptotic cells was much higher than that in the CON groups（P〈0.01）.The DIO＋LOM group mice showed fewer apoptosis cells and the percentage of apoptotic cells in this group were significantly decreased than the DIO mice （ P 〈0.05 ）. The Laser scanning confocal microscope detection showed Ca2＋staining intensity of RGCs in DIO group increased and its staining intensity ratio was significantly higher than in CON group （ P〈0.01 ） , the Ca2＋ staining intensity and its staining intensity ratio in DIO＋LOM group were significantly decreased than the DIO group （P〈0.01）. CONCLUSION： Lomerizine has neuroprotective effects on damage of retinal ganglion cells in diet-induced obesity mice, which may be related tothe attenuatio n of intracellular Ca2＋overload.