木犀草素对糖尿病性白内障大鼠的晶状体保护作用及对MEK/ERK信号通路的影响研究

Protective effect of luteolin on lens and MEK/ERK signal pathway in diabetic cataract rats

目的:研究木犀草素对糖尿病性白内障大鼠的晶状体保护作用及对MEK/ERK信号通路的调节作用。方法:将60只大鼠随机分为正常对照组、白内障组以及木犀草素低、中、高剂量组,每组12只,采用腹腔注射链脲佐菌素(STZ)溶液(60 mg/kg)方法建立糖尿病性白内障模型大鼠,木犀草素低、中、高剂量组分别按照20 mg/kg、40 mg/kg、80 mg/kg灌胃给予大鼠木犀草素,正常对照组及白内障组给予生理盐水,1次/d,连续12周,测定给药前后大鼠血糖水平、晶状体浑浊度、晶状体过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)水平,苏木精-伊红(HE)染色法检查大鼠晶状体病理学改变,实时荧光定量PCR(qPCR)测定晶状体MEK mRNA和ERK mRNA水平,蛋白质免疫印迹(Western blot)测定晶状体MEK及ERK蛋白水平。结果:与正常对照组比较,白内障组大鼠血糖水平、晶状体浑浊度、晶状体MEK mRNA和ERKmRNA以及晶状体MEK和ERK蛋白水平显著升高(P<0.05),晶状体CAT、GSH-Px、SOD水平显著降低(P<0.05);与白内障组大鼠比较,木犀草素低、中、高剂量组大鼠血糖水平、晶状体浑浊度、晶状体MEK mRNA和ERK mRNA以及MEK和ERK蛋白水平显著降低(P<0.05),晶状体CAT、GSH-Px、SOD水平显著升高(P<0.05),晶状体病理学明显改善,且各指标变化与木犀草素的剂量呈依赖性。结论:木犀草素能够改善糖尿病性白内障大鼠的晶状体病理学变化,抑制晶状体氧化损伤,其机制可能与调节MEK/ERK信号通路有关。

Objective:To study the protective effect of luteolin on lens and regulation of MEK/ERK signal pathway in diabetic cataract rats.Methods:60 rats were randomly divided into normal control group,cataract group,low,middle and high dose luteolin groups,12 rats in each group.Diabetic cataract model rats were established by intraperitoneal injection of STZ solution(60mg/kg).Low,middle and high dose luteolin groups were given intragastric administration of 20mg/kg,40mg/kg,and 80mg/kgluteolin,respectively.Normal control group and cataract group were given normal saline.Blood glucose level,lens turbidity,lens catalase(CAT),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)levels were measured before and after administration.The pathological changes of rat lens were examined by hematoxylin-eosin(HE)staining.The mRNA levels of lens MEK and ERK were measured by real-time quantitative polymerase chain reaction(qPCR).The protein levels of MEK and ERK in lens were measured by Western blotting.Results:Compared with the normal control group,the levels of blood glucose,lens turbidity,mRNA and proteinlevels of MEK and ERK in cataract group were significantly increased,while CAT,GSH-Px and SOD levels were significantly decreased(P<0.05).Compared with cataract group,the levels of blood glucose,lens turbidity,mRNA and protein levels of MEK and ERK decreased significantly,but CAT,GSH-Px and SOD levels increased significantly in luteolin low,middle and high dose group(P<0.05).Lens pathology was significantly im-proved;moreover,the changes of each index were dependent on the dose of luteolin.Conclusion:Luteolin can improve the lens pathological changes and inhibit lens oxidative damage in diabetic cataract rats.The mechanism may be related to the regulation of MEK/ERK signal pathway.