白藜芦醇对糖尿病大鼠内耳损伤的保护作用及机制研究  

The Protective Effects and Its Mechanisms of Resveratrol on Inner Ear Damage in Diabetes Rats

作　　者：高海涛[1] 曲雁[1] 张勋[1] 穆俊晌[1] 张璞[1] 王欣[1] 赵秀棉 Gao Haitao;Qu Yan;Zhang Xun;Mu Junshang;Zhang Pu;Wang Xin;Zhao Xiumian(Department of Otolaryngology,the Third Hospital ofHebei Medical University,Shijiazhuang,050000,China)

机构地区：[1]河北医科大学第三医院耳鼻喉科,石家庄050000 [2]河北省平泉县医院耳鼻喉科

出　　处：《听力学及言语疾病杂志》2018年第4期409-413,共5页Journal of Audiology and Speech Pathology

基　　金：河北省卫计委科研基金项目(No:ZD20140012)

摘　　要：目的探讨白藜芦醇对糖尿病大鼠内耳损伤的保护作用及可能机制。方法健康SD大鼠60只,随机分成对照组、模型组、高剂量治疗组、低剂量治疗组,每组15只。模型组及高、低剂量治疗组大鼠先采用股静脉注射链脲佐菌素和高脂饮食建立糖尿病模型;然后高、低剂量治疗组大鼠分别给予100mg·kg^(-1)·d^(-1)、50mg·kg^(-1)·d^(-1)白藜芦醇灌胃,其余组均给予等量生理盐水灌胃,连续4个月;检测各组空腹血糖、血浆胆固醇及甘油三酯水平;检测内耳组织中超氧化物歧化酶、过氧化氢、丙二醛及过氧化氢酶等氧化应激指标水平;利用伊凡思蓝检测内耳血管通透性;免疫组化法和Western blot观察内耳组织血管内皮生长因子(vascular endothelial growth factor,VEGF)、细胞间粘附分子-1(intercellular adhesion molecule,ICAM-1)及耳蜗组织凋亡促进因子caspase-3、Bax及凋亡抑制因子Bcl-2等蛋白表达。结果与对照组比较,模型组大鼠内耳血管通透性明显增强,血糖、血脂水平显著上升,内耳组织超氧化物歧化酶和过氧化氢酶表达下降、而丙二醛及过氧化氢表达增加,VEGF、ICAM-1、caspase-3、Bax蛋白表达水平显著上调,Bcl-2表达水平明显下降,差异均有统计学意义(均为P<0.05);与模型组比较,高、低剂量治疗组大鼠经白藜芦醇干预后,血管通透性明显减弱,血糖、血脂水平明显下降,内耳组织超氧化物歧化酶和过氧化氢酶表达上升,而丙二醛及过氧化氢表达减少,VEGF、ICAM-1、caspase-3、Bax蛋白表达水平显著下调,Bcl-2表达水平则明显上升,差异均有统计学意义(均为P<0.05)。结论白藜芦醇可通过抗氧化应激、抑制VEGF和ICAM-1表达、抑制细胞凋亡等,对糖尿病大鼠内耳损伤起保护作用。Objective To study the protective effects of resveratrol on the inner ear damage in diabetes rats,and explore its possible mechanisms.Methods Sixty rats were used in our study and equally randomized into control group,model group,high-and low-dose treatment groups.Firstly,the diabetic rat model was developed using streptozotocin plus high-fat diet in model group and two treatment groups,then,rats in high-and low-dose groups were orally administered resveratrol at a dose of 100,50 mg·kg-1·d-1 respectively,the duration time of drug administration was 4 months,the other groups were orally administered isometric sterile water at the same time.The fasting blood glucose,total cholesterol and triglyceride levels were detected.The oxidative stress indexes of inner ear tissue were analyzed.The inner ear vascular permeability was measured through labeling with evans blue.Protein level of VEGF,ICAM-1 and caspase-3 in inner ear tissue were determined by immunohistochemical method and/or Western blot.Results Compared with control group,the inner ear vascular permeability,fasting blood glucose,total cholesterol and triglyceride levels and oxidative stress indexes in model group were markedly increased(all P<0.05).The protein expression level of VEGF,ICAM-1,caspase-3,Bax were significantly increased(all P<0.05),and the protein expression level of Bcl-2 were significantly decreased(P<0.05).After resveratrol intervention for 4 months,the inner ear vascular permeability,fasting blood glucose,total cholesterol and triglyceride levels and oxidative stress indexes in two treatment groups were markedly decreased(all P<0.05).Compared to the model group,the protein expression level of VEGF,ICAM-1,caspase-3,Bax were also significantly decreased(all P<0.05),and the protein expression level of Bcl-2 were significantly increased(P<0.05).Conclusion Resveratrol can play a protective role in diabetes-induced inner ear damage by relieving oxidative stress,reducing protein expression of VEGF and ICAM-1,inhibiting apoptosis of inner ear cel

关 键 词：白藜芦醇 糖尿病 内耳损伤 大鼠 

分 类 号：R764.5[医药卫生—耳鼻咽喉科]