标题:Ⅱ型糖尿病大鼠白内障的ERK通路介导机制及其抑制剂PD98059的改善作用
作者:肖 涵,刘文斌,万 丽
(南京明基医院眼科,江苏 南京 210019)
卷次:
2015年26卷7期
【摘要】 目的 分析 ERK通路在Ⅱ型糖尿病大鼠白内障发生中的参与机制及 PD98059的改善作用。
方法 35只 SD大鼠随机分为对照组、糖尿病组、PD98059低剂量、中剂量和高剂量组(每组 7只)。小剂量
STZ联合高糖高脂饮食 120 d复制糖尿病大鼠白内障模型,第 64天每天对各组大鼠尾静脉注射生理盐水或
PD98059。分析各组大鼠晶状体状态及胰岛素抵抗系数HOMA-IR的变化,Real-time PCR和Western blotting分
析晶状体中ERK通路相关蛋白ERK1/2、p-ERK1/2、p38及内质网应激蛋白ATF6、PERK的表达变化。结果 与
对照组大鼠比较,糖尿病组大鼠晶状体明显浑浊,HOMA-IR明显增高,晶状体组织中 p-ERK1/2、p38、PERK和
ATF6表达上调,而总ERK的表达未发生变化。PD8059可以显著改善上述晶状体及相关蛋白表达的异常,且具
有剂量依从性。结论 激活的ERK信号通路参与了Ⅱ型糖尿病大鼠白内障发病过程,PD95059通过抑制上调表
达的p38-pERK1/2及内质网应激起缓解作用。
【关键词】 Ⅱ型糖尿病;白内障;ERK通路;PD98059
【中图分类号】 R-332 【文献标识码】 A 【文章编号】 1003—6350(2015)07—0944—04
Involvement of ERK pathway in cataract in typeⅡ diabetes and alleviations of PD98059, inhibitor of ERK.
XIAO
Han, LIU Wen-bin, WAN Li. Department of Ophthalmology, Nanjing Benq Hospital, Nanjing 210019, Jiangsu, CHINA
【Abstract】 Objective To explore the involvement of ERK pathway in the pathogenesis of type Ⅱ diabetic
cataract and the interventions of PD98059 (the inhibitor of ERK). Methods Thirty-five male SD rats were divided in-
to five groups: control group, diabetic group, low/middle/high dose of PD98059 group (n=7 in each group). The type
Ⅱ diabetic cataract model was duplicated by low dose of STZ injections combined with high content of fat and sugar
diet for 120 d. All the rats were administrated with normal saline or PD98059. The HOMA-IR was calculated in each
group. And at the same time, the expression of ERK1/2, p-ERK1/2, p38, ATF6 and PERK were detected by Western
blotting or real-time PCR. Results The HOMA-IR in diabetic group was increased greatly with cloudy lens when
compared to the control group. The expression of p-ERK1/2, p38, ATF6 and PERK were up-regulated dramatically in
diabetic group, while the expression of total ERK has no change. PD98059 alleviated the cloudy lens in diabetic rats
significantly and normalized the aforementioned abnormal proteins greatly. Conclusion Activated ERK pathway and
endoplasmic reticulum stress are involved in the pathogenesis of cataract in type Ⅱdiabetes. PD98059 alleviates the
cataract by inhibiting the aforementioned parameters in a dose dependent manner.
【Key words】 TypeⅡ diabetes; Cataract; ERK pathway; PD98059
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