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首页|期刊导航|中国药物经济学|金樱子滴眼液对糖尿病性白内障大鼠晶状体氧化应激及p38 MAPK信号通路的调节作用

金樱子滴眼液对糖尿病性白内障大鼠晶状体氧化应激及p38 MAPK信号通路的调节作用OA

Regulatory Effect of Rosa Laevigata Michx.Eye Drops on Oxidative Stress and p38 MAPK Signal Pathway in Lens of Diabetic Cataract Rats

中文摘要英文摘要

目的 探讨金樱子滴眼液对糖尿病性白内障大鼠晶状体氧化应激及p38 MAPK信号通路的调节作用.方法 将35只 SD 雄性大鼠随机分为对照组、糖尿病性白内障模型组以及金樱子滴眼液低剂量干预组、金樱子滴眼液中剂量干预组、金樱子滴眼液高剂量干预组,每组7 只.经腹腔注射65 mg/kg链脲佐菌素(STZ)溶液建立糖尿病性白内障模型,金樱子滴眼液干预组分别以浓度为0.01 mg/ml、0.05 mg/ml、0.1 mg/ml的金樱子滴眼液滴眼,4 次/d,连续干预12 周.每周检测大鼠体重,第 6、12 周利用裂隙灯观察晶状体混浊程度.干预结束后,收集大鼠两侧眼球晶状体,检测晶状体组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平;采用蛋白质免疫印迹法检测晶状体组织中凋亡蛋白Bcl-2、Bax,以及p38 MAPK信号通路蛋白p38 MAPK、p-p38 MAPK、MKK6 及p-MKK6 表达水平.结果 给药前各组大鼠体重比较差异无统计学意义(P>0.05);给药干预期间,模型组大鼠体重明显低于对照组(P<0.05),干预组大鼠体重高于模型组(P<0.05).模型组晶状体混浊程度高于对照组(P<0.05),干预组大鼠治疗后晶状体混浊程度低于模型组(P<0.05).模型组大鼠晶状体中MDA水平高于对照组(P<0.05),SOD和GSH-Px水平低于对照组(P<0.05);治疗后干预组MDA水平低于模型组,SOD和GSH-Px水平高于模型组,差异有统计学意义(P<0.05).模型组大鼠晶状体中凋亡蛋白 Bcl-2 表达水平低于对照组(P<0.05),Bax 蛋白表达水平高于对照组(P<0.05),Bcl-2/Bax 值小于对照组(P<0.05);治疗后干预组晶状体中凋亡蛋白Bcl-2 表达水平高于模型组(P<0.05),Bax蛋白表达水平低于模型组(P<0.05),Bcl-2/Bax值高于模型组(P<0.05).模型组大鼠晶状体中p-MKK6 和p-p38 MAPK蛋白表达水平,p-MKK6/MKK6和p-p38 MAPK/p38 MAPK高于对照组(P<0.05);治疗后干预组p-MKK6、p-p38 MAPK蛋白表达水平,p-MKK6/MKK6和p-p38 MAPK/p38 MAPK低于模型组(P<0.05).结论 金樱子滴眼液能够改善糖尿病性白内障大鼠晶状体混浊程度,保护晶状体,抑制细胞凋亡,延缓病情进展,其机制可能与抑制氧化应激介导的p38 MAPK信号通路相关.

Objective To study the regulatory effect of Rosa laevigata Michx.(RLM)eye drops on oxidative stress and p38 MAPK signal pathway in lens of diabetic cataract rats.Methods 35 male SD rats were randomly divided into the control group(CG),the diabetic cataract model group(DC),RLM low-dose group,RLM medium-dose group and RLM high-dose group,with 7 rats in each group.The diabetic cataract model was established by intraperitoneal injection of 65mg/kg streptozotocin.The RLM eye drop intervention group(IG)was treated with RLM eye drop at 0.01mg/ml,0.05 mg/ml and 0.1 mg/ml,4 times a day for 12 weeks.The weight of rats were measured weekly,and the opacity of the lens was observed by slit-lamp at the 6th and 12th week.After the intervention,the levels of malondialdehyde,superoxide dismutase and glutathione peroxidase in the lens tissues of rats were detected.The expression levels of apoptotic proteins Bcl-2 and Bax,as well as p38 MAPK,p-p38 MAPK,MKK6 and p-MKK6 signaling pathway proteins were detected by Western blot.Results There was no significant difference in body weight among all groups before administration(P>0.05).During the intervention period,the body weight of rats in the model group was significantly lower than that in the control group(P<0.05),and the body weight of rats in the intervention group was higher than that in the model group(P<0.05).The opacity of lens in the model group was higher than that in the control group(P<0.05),and the opacity of lens in the intervention group was lower than that in the model group after treatment(P<0.05).MDA levels in the lens of rats in model group were higher than those in control group(P<0.05),while SOD and GSH-Px levels were lower than those in control group(P<0.05).After treatment,the MDA level in the intervention group was lower than that in the model group,and the SOD and GSH-Px levels were higher than that in the model group,with statistical significance(P<0.05).The expression level of apoptosis protein Bcl-2 in lens of model group was lower than that of control group(P<0.05),the expression level of Bax protein was higher than that of control group(P<0.05),and the value of Bcl-2/Bax was lower than that of control group(P<0.05).After treatment,the expression level of apoptosis protein Bcl-2 in the lens of the intervention group was higher than that of the model group(P<0.05),the expression level of Bax was lower than that of the model group(P<0.05),and the value of Bcl-2/Bax was higher than that of the model group(P<0.05).The expression levels of P-MKK6 and P-P38 MAPK protein in lens of model group were higher than those of control group(P<0.05).After treatment,the expression levels of P-MKK6 and P-P38 MAPK protein in the intervention group were lower than those in the model group(P<0.05).Conclusion By inhibiting p38 MAPK signaling pathway,lens oxidative stress and apoptosis,the RLM eye drops may improve lens function and delay the progression of diabetic cataract in rats.

罗淑仪;梁燕云;刘瑶玉;黄勇梅;罗嘉莉;李霭燕;张华康

广州市番禺区妇幼保健院药剂科,广州 511400广州医科大学附属第二医院药剂科,广州 510220广州市番禺区中医院检验科,广州 511400广州市番禺区中医院药剂科,广州 511400

临床医学

金樱子糖尿病性白内障氧化应激p38 MAPK信号通路

Golden cherryDiabetic cataractOxidative stressP38 MAPK signal path

《中国药物经济学》 2024 (005)

60-65 / 6

广州市番禺区科技计划项目(2022-Z04-059)

10.12010/j.issn.1673-5846.2024.05.010

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