摘要目的 观察泛素蛋白酶体抑制剂对早期糖尿病性视网膜病变(DR)中激活核转录因子(NF-κB)和其抑制性信号蛋白IκB激酶的降解调控作用,及其对视网膜神经节细胞(RGC)凋亡的影响.方法 健康成年雄性Wistar大鼠40只,用数字随机法随机分为正常对照组(A组)、DR安慰剂组(B组)、DR+蛋白酶体抑制剂(MG132)低浓度干预组(C组),DR+MG132高浓度干预组(D组),每组10只大鼠.给药后6、8周,检测每组大鼠体重、血糖,并制备视网膜石蜡切片,采用免疫组织化学法分析NF-κB及其抑制性信号蛋白IκB在大鼠视网膜中的表达.采用原位凋亡检测(TUNEL)法分析RGC的凋亡情况.结果 NF-κB在B组表达较A组明显增强,D组表达强度较B组减弱;IκB在B组表达较A组明显减少,D组表达强度较B组增强;RGC凋亡在B组的表达较A组明显增多,D组表达强度较B组减少;差异均有统计学意义(P<0.01).C组NF-κB和IKB的表达强度及RGC凋亡与B组相比,差异均无统计学意义(P<0.05).结论 泛素蛋白酶体抑制剂MG132通过抑制IKB泛素化降解,阻断NF-κB激活,抑制RGC的凋亡.

abstractsObjective To observe the degradation regulation of ubiquitin-proteasome inhibitor nuclear factor κB(NF-κB)and its inhibitory signal protein IκB kinase in earlier period diabetic retinopathy(DR), and the effects on retinal ganglion cells (RGC) apoptosis. Methods Forty healthy adult Wistar rats were randomly divided into control (group A), DR(group B), DR+low-concentration MG132-treated (group C) and DR+high-concentration MG132-treated(group D)groups, 10 rats in each group. After 6 and 8 weeks, the results of body masses and fasting blood glucose (FBG) were detected, the expression of NF-κB and IκB were observed by immunohistoehemistry respectively. RGC apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) method. Results The expression of NF-κB was up-regulated in group B compared with group A, its expression decreased in group D compared with group B; but the expression of IκB was contrary to NF-κB; RGC apoptosis was followed a similar pattern with the expression of NF-κB; the differences among them were statistically significant (P< 0. 01). Compared the expression of NF-κB, IκB and RGC apoptosis in group C and D, there were no statistically significant differences (P>0. 05). Conclusion Ubiquitin-proteasome inhibitor MG132 can block the activation of NF-κB, inhibit ubiquitination of IκB degradation and RGC apoptosis.