罗格列酮对糖尿病大鼠视网膜神经节细胞凋亡的影响

目的　观察过氧化物酶体增生物激活受体-γ（ｐｅｒｏｘｉｓｏｍｅｐｒｏｌｉｆｅｒａｔｏｒ-ａｃｔｉｖａｔｅｄｒｅｃｅｐｔｏｒ-γ，ＰＰＡＲ-γ）激动剂罗格列酮对链脲佐菌素诱导的早期糖尿病（ｄｉａｂｅｔｅｓｍｅｌｌｉｔｕｓ，ＤＭ）大鼠视网膜神经节细胞（ｒｅｔｉｎａｌｇａｎｇｌｉｏｎｃｅｌｌｓ，ＲＧＣｓ）凋亡的影响，进而从分子学水平上阐明ＰＰＡＲ-γ激动剂对糖尿病视网膜病变（ｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ，ＤＲ）的保护作用，为预防及早期治疗ＤＲ提供一种新思路。方法　选择９０只健康的雄性Ｗｉｓｔａｒ大鼠随机分为三组:正常对照组、ＤＭ＋罗格列酮组和ＤＭ组，进一步将每组大鼠分为给药后４周、８周和１２周三个时间点进行观察。采用一次性腹腔注射５０ｍｇ?ｋｇ－１链脲佐菌素的方法建立ＤＭ大鼠模型。自ＤＭ模型成模后第３天起，ＤＭ＋罗格列酮组大鼠每天给予罗格列酮３ｍｇ?ｋｇ－１灌胃，正常对照组和ＤＭ组每天给予等体积的生理盐水灌胃。于给药后４周、８周和１２周处死各组大鼠，处死前测各组大鼠的血糖和体质量，然后摘除左眼球制成眼杯，采用ＴＵＮＥＬ法测定各组大鼠视网膜上ＲＧＣｓ的凋亡指数，并作对比。结果　给药后４周、８周和１２周，ＤＭ组和ＤＭ＋罗格列酮组大鼠血糖水平均明显高于正常对照组（均为Ｐ＜０．０１）；ＤＭ组和ＤＭ＋罗格列酮组大鼠的体质量均较正常对照组降低（均为Ｐ＜０．０５）。正常对照组大鼠ＲＧＣ层上仅见少量的凋亡细胞；各时间点ＤＭ＋罗格列酮组大鼠ＲＧＣｓ的凋亡指数较ＤＭ组明显降低（均为Ｐ＜０．０１）；ＤＭ组和ＤＭ＋罗格列酮组大鼠ＲＧＣｓ的凋亡指数均明显高于正常对照组（均为Ｐ＜０．０１）。结论　外源性ＰＰＡＲ-γ激动剂罗格列酮能够抑制ＤＭ大鼠视网膜上ＲＧＣｓ的凋亡，对早期ＤＭ大鼠视网膜具有保护作用，有望成为ＤＲ新的治疗手段。

Effects of rosiglitazone on retinal ganglion cells apoptosis in rats with diabetes mellitus

Objective To investigate the effects of peroxisome proliferator-activated receptor-gamma ( PPAR-7) excitomotor , rosiglitazone , on apoptosis of the retinal ganglion cells ( RGCs) in the retina in diabetes mellitus ( DM) induced by streptozotocin.then set out the protective effect of the PPAR-7 agonists on DR from molecular level, and provide a new way for prevention and early treatment DR. Methods Ninety male Wistar rats were divided into three groups randomly : Normal control group, DM group and DM + rosiglitazone group ,30 rats in each group. Each group was observed at 4 weeks ,8 weeks and 12 weeks. DM model was established by intraperitoneal injection of 50 mg . kg -l STZ. 3 mg . kg -l of rosiglitazone was intragastricly administered once per day in DM + rosiglitazone group and the same volume of NS was intragastricly administered once per day in control group and DM group after modeling 3 days. After measured blood glucose and weight at 4 weeks , 8 weeks and 12 weeks , the rats were sacrificed and removed left eyeball to make the eye cups. The apoptotic index of the retinal ganglion cells was detected by TUNEL. Results The blood glucose level at 4 weeks .8 weeks and 12 weeks were sigruficantly elevated in DM group and DM + rosiglitazone group compared with control group ( all P < 0. 01 ) . The weight of rats was decreased in DM group and DM + rosiglitazone group compared with control group ( all P < 0. 05 ) . There were few apoptotic cells in rat retina of control group. Compared with DM group ,the apoptosis index of DM + rosiglitazone group at each time points was significantly reduced ( all P < 0. 01 ) . The apoptosis index of RGCs in rat retina was significantly elevated at various time points in DM group and DM + rosiglitazone group compared with control group ( all P < 0. 01) . Conclusion Rosiglitazone as one of the peroxisome proliferator-activated receptor-gamma excitomotors can inhibit apoptosis of RGCs in rat with DM. It is expected to become one of the new therapeutic methods because it protect retina in rat with DR.