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郑辉,常宝成,葛焕琦,张春风,李雪粉.网膜素能降低糖尿病动脉硬化大鼠主动脉胶原Ⅲ含量[J].中国动脉硬化杂志,2019,(3):190~196
网膜素能降低糖尿病动脉硬化大鼠主动脉胶原Ⅲ含量
Omentin can reduce the content of collagenⅢ in aorta of diabetic atherosclerosis rats
投稿时间:2018-07-27  修订日期:2018-09-21
DOI:
中文关键词:  网膜素  糖尿病  动脉硬化  胶原  基质金属蛋白酶  氧化应激  大鼠
英文关键词:omentin  diabetes  arteriosclerosis  collagen  matrix metalloproteinase  oxidative stress  rat
基金项目:国家自然科学基金(81774043);天津市滨海新区重点支持项目(2013BWKZ006)
作者单位E-mail
郑辉 国家卫生健康委员会激素与发育重点实验室 天津市代谢性疾病重点实验室 天津医科大学代谢病医院内分泌研究所, 天津市,300070
泰达国际心血管病医院内分泌科,天津市 300457 
e-mail为zhui0123@163.com,e-mail为16464768@qq.com 
常宝成 国家卫生健康委员会激素与发育重点实验室 天津市代谢性疾病重点实验室 天津医科大学代谢病医院内分泌研究所, 天津市,300070 e-mail为zhui0123@163.com,e-mail为16464768@qq.com 
葛焕琦 泰达国际心血管病医院内分泌科,天津市 300457  
张春风 泰达国际心血管病医院内分泌科,天津市 300457  
李雪粉 泰达国际心血管病医院内分泌科,天津市 300457  
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中文摘要:
      目的 探讨过表达网膜素对糖尿病动脉硬化大鼠主动脉胶原含量的影响。方法 选用60只1月龄雄性Wistar大鼠,按随机数字表法分为正常对照组(NC组;n=8)和实验组(n=52)。实验组采用高脂高糖饲料喂养联合尾静脉注射2%链脲佐菌素(30 mg/kg),建立糖尿病大鼠模型;成模的糖尿病大鼠再灌胃给予维生素D3(70万IU/kg),继续喂养16周,建立糖尿病合并动脉硬化大鼠模型。将最终24只糖尿病动脉硬化大鼠,依随机数字表法分为糖尿病动脉硬化组(DAC组;n=8)、糖尿病动脉硬化+空病毒组(DAC+E组;n=8)和糖尿病动脉硬化+网膜素组(DAC+O组;n=8)。将150 μL携带人网膜素基因ITLN1-AAV9的腺相关病毒和携带空质粒的病毒经尾静脉分别注射至DAC+O组和DAC+E组,等量生理盐水注射至NC组和DAC组。继续高脂饲料喂养4周,处死大鼠,测定血清及肝脏网膜素、血脂水平;取主动脉进行HE染色;应用定量实时聚合酶链反应测定胶原Ⅰ、Ⅲ、基质金属蛋白酶2(MMP-2)、MMP-9 mRNA含量;Western blot测定主动脉胶原Ⅰ、Ⅲ、MMP-2、MMP-9蛋白含量;黄嘌呤氧化酶法测定主动脉超氧化物歧化酶(SOD)含量,硫代巴比妥酸缩合法测定主动脉丙二醛(MDA)水平。结果 (1)与NC组相比,糖尿病动脉硬化大鼠血清中大鼠网膜素水平显著下降。给予携带人网膜素基因的腺相关病毒静脉注射后,在DAC+O组的大鼠血清中测定人网膜素为(101.0±0.2) μg/L,肝脏中测得人网膜素为(98.3±1.9) μg/L,在其他组别的相应组织中未测出人网膜素。(2)与DAC组相比,DAC+E组和DAC+O组血清血脂谱和主动脉MDA均显著下降,SOD升高,但后2组间差异无统计学意义。(3)DAC组主动脉内膜部分脱落,平滑肌增生,局部透明变性并钙化。DAC+O组内膜完整,局部管壁增厚,平滑肌增生和钙化程度较DAC组明显改善。(4)与DAC+E组相比,DAC+O组胶原Ⅰ、Ⅲ mRNA表达显著下降,胶原Ⅲ蛋白表达显著下降。与DAC+E组相比,DAC+O组MMP-2、MMP-9的mRNA和蛋白表达差异均无统计学意义。结论 在糖尿病动脉硬化大鼠体内,过表达人网膜素能减少主动脉胶原Ⅲ的表达量,减轻动脉硬化,对氧化应激水平无明显影响。
英文摘要:
      Aim To investigate the effect of overexpression of omentin on collagen content in aorta of diabetic atherosclerosis rats. Methods 60 one-month-old male Wistar rats were randomly divided into normal control group (NC group; n=8) and experimental group (n=52). The experimental group was fed with high-fat and high-sugar diet and injected 2% streptozotocin (30 mg/kg) into tail vein to establish diabetic rat model. The diabetic rats were fed with vitamin D3 (0,0 IU/kg) for 16 weeks to establish a diabetic rat model with arteriosclerosis. 24 diabetic atherosclerosis rats were randomly divided into diabetic atherosclerosis group (DAC group; n=8), diabetic atherosclerosis plus empty virus group (DAC+E group; n=8) and diabetic atherosclerosis plus omenin group (DAC+O group; n=8). 150 μL adeno-associated virus carrying human omentin gene ITLN1-AAV9 and 150 μL virus carrying empty plasmid were injected into DAC+O group and DAC+E group via tail vein, respectively, and equivalent physiological saline was injected into NC group and DAC group. The rats were fed with high-fat diet for 4 weeks. The serum and liver omentin and blood lipid levels were measured. The aorta was taken for HE staining. Quantitative real-time polymerase chain reaction was used to determine the contents of collagen Ⅰ, Ⅲ, matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA. Protein contents of collagen Ⅰ, Ⅲ, MMP-2 and MMP-9 in aorta were determined by Western blot. The content of aortic superoxide dismutase (SOD) was determined by xanthine oxidase method. Aortic malondialdehyde (MDA) levels were measured by thiobarbituric acid condensation method. Results (1)Compared with NC group, the level of serum omentin in diabetic atherosclerosis rats decreased significantly. After intravenous injection of adeno-associated virus carrying human omentin gene, in DAC+O group, the serum and liver levels of human omentin were 101.0±0.2 and 98.3±1.9 μg/L, respectively. Human omentin was not detected in corresponding tissues of other groups. (2)Compared with DAC group, serum lipid profile and aortic MDA in DAC+E group and DAC+O group decreased significantly, while SOD increased, but there was no significant difference between the latter two groups. (3)In DAC group, aortic intima was partially exfoliated, smooth muscle was proliferated, local hyalinization and calcification were observed. In DAC+O group, the intima was intact, the local wall was thickened, the degree of smooth muscle proliferation and calcification was significantly improved compared with DAC group. (4)Compared with DAC+E group, the expressions of collagen Ⅰ and Ⅲ mRNA and collagen Ⅲ protein in DAC+O group decreased significantly. Compared with DAC+E group, there was no significant difference in the expressions of MMP-2, MMP-9 mRNA and protein in DAC+O group. Conclusion In diabetic atherosclerosis rats, overexpression of human omentin can reduce the expression of collagen Ⅲ in aorta, alleviate atherosclerosis, and has no significant effect on oxidative stress level.
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