MEK/ERK信号转导通路在大鼠糖尿病白内障中的作用

目的分析丝裂原细胞外信号调节激酶(mitogen extracellular signal-regulated kinase,MEK)/细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)信号转导通路在大鼠糖尿病白内障中的发病机制,为相关药物研发及临床治疗提供参考。方法 60只SPF级SD大鼠随机分为正常对照组、模型组和PD98059处理组,后两组大鼠腹腔注射链脲佐菌素(streptozotocin,STZ)诱导糖尿病模型,PD98059处理组于造模前1 d前房内注射2.5μg(5μL)的PD98059,正常对照组与模型组大鼠前房内仅注射PBS。注射STZ后每日观察大鼠晶状体透明度,并于注射STZ后8周时取大鼠尾血检测血糖、总胆固醇,Western blot检测晶状体内MEK/ERK信号转导通路相关蛋白Ras、Raf、MEK和ERK1/2的表达。结果模型组大鼠注射STZ后4周晶状体开始出现周边空泡增多、絮状混浊,8周后整个晶状体明显混浊,而PD98059处理组大鼠晶状体的混浊程度较模型组有所减轻。与正常对照组相比,模型组大鼠的血糖(28.70±3.33)mmol·L^-1]、总胆固醇(2.53±0.74)mmol·L^-1]及Ras(0.67±0.12)、Raf(0.50±0.13)、MEK(0.48±0.10)和ERK1/2(0.59±0.15)蛋白相对表达量均明显升高,差异均有统计学意义(均为P<0.05);PD98059处理组大鼠的血糖(20.60±4.18)mmol·L^-1]、总胆固醇(2.30±0.64)mmol·L^-1]及Ras(0.49±0.11)、Raf(0.44±0.09)、MEK(0.35±0.08)和ERK1/2(0.48±0.14)蛋白相对表达量均较模型组显著降低,但仍高于正常对照组,差异均有统计学意义(均为P<0.05)。结论 MEK/ERK信号转导通路的激活参与了糖尿病大鼠白内障的发病过程。

Pathogenesis of cataract in diabetic rats involved in MEK/ERK signal transduction pathway

Objective　To analyze the pathogenesis of mitogen extracellular signal-regulated kinase（MEK）/extracellular regulated protein kinases（ERK） induced diabetic cataract in rats and provide reference for research of related drugs and clinical treatment.Methods　Totally 60 clean SD rats were divided into three groups randomly:control group （n=20），diabetic model group （n=20） and PD98059 treated group （n=20）.Diabetic rats were induced by intraperitoneal injection of streptozotocin （STZ） in the last two groups.Rats in the control group and diabetic model group were given PBS and rats in PD98059 treated group were given PD98059 2.5 μg （5 μL） in anterior chamber one day before injection of STZ.Rat lens were observed every day after injection of STZ.The blood glucose，total cholesterol and the expression of MEK/ERK signal transduction pathway related proteins （Ras，Raf，MEK，ERK1/2） in rat lens were analyzed by Western blot 8 weeks after injection of STZ.Results　In the diabetic model group，4 weeks after injection of STZ the lens showed flocculent opacity，increased peripheral vacuoles，and 8 weeks after injection of STZ the whole lens became obvious opacity.While in the PD98059 treated group，the degree of lens opacity decreased compared with the diabetic model group.Compared with the control group，the levels of blood glucose ［（28.70±3.33）mmol·L^-1］，total cholesterol ［（2.53±0.74）mmol·L^-1］，Ras （0.67±0.12），Raf（0.50±0.13），MEK（0.48±0.10） and ERK1/2 （0.59±0.15） protein in the diabetic model group were significantly enhanced （all P<0.05）.The glucose ［（20.60±4.18）mmol·L^-1］，total cholesterol ［（2.30±0.64） mmol·L^-1］，and the expression levels of Ras （0.49±0.11），Raf （0.44±0.09），MEK （0.35±0.08） and ERK1/2 （0.48±0.14） protein in the PD98059 treated group were significantly decreased when compared with the diabetic model group，which were still higher than those of the control group （all P<0.05）.Conclusion　Activation of MEK/ERK signaling pathway is involved in the pathogenesis of cataract in diabetic rats.