芝麻素改善自发性高血压大鼠脑海马、皮层氧化应激的机制研究

发布时间：2018-07-10 11:34

本文选题：芝麻素 + 自发性高血压大鼠　；参考：《皖南医学院》2016年硕士论文

【摘要】：目的:探讨芝麻素改善自发性高血压大鼠脑海马、皮层氧化应激的机制。方法:16周龄SHR 40只,WKY 10只,适应性喂养2周。SHR随机分为4组:Ses高剂量(160mg/kg/d,n=10)组、Ses低剂量(80mg/kg/d,n=10)组、阳性Cap(30mg/kg/d,n=10)组及SHR(0.5%羧甲基纤维素钠5ml/kg/d,n=10)组。另设WKY(0.5%羧甲基纤维素钠5ml/kg/d,n=10)为正常对照组。于每日下午5时灌胃给药,每日给药一次,连续给药12周。给药前及给药后每2周测量清醒静息状态下大鼠的尾动脉舒张压(DBP,mm Hg)。于末次给药后,禁食12小时,腹腔麻醉,用咬骨钳剥离颅骨,取出全脑制作标本。尼氏染色法观察海马、皮层神经元结构病理变化并进行细胞计数;比色法和ABTS法分别测定脑海马、皮层组织匀浆H2O2和T-AOC的含量;黄嘌呤氧化酶法和硫代巴比妥酸比色法分别测定脑海马、皮层组织匀浆SOD和MDA的含量;硝酸还原酶法分别测定脑海马、皮层组织匀浆NO的含量;免疫组织化学法观察海马、皮层n NOS阳性蛋白颗粒表达;Western Blot(免疫印迹)检测大鼠海马、皮层n NOS、NADPH氧化酶亚基p22phox及p47phox的蛋白表达。结果:(1)(1)与WKY组相比,SHR组DBP均明显升高(P0.05或P0.01;(2)与SHR组相比,芝麻素高低剂量组和卡托普利组的DBP随给药时间延长明显降低(P0.05或P0.01),芝麻素高低剂量组给药10周后血压趋于稳定。(2)(1)与正常对照组相比,自发性高血压大鼠模型组海马锥体细胞排列疏松不均,形态不规则,且细胞数量减少,细胞空染或淡染。与模型组相比,Ses 80mg/kg和160mg/kg剂量组及Cap组的空染或淡染细胞均有不同程度的减少,且神经元排列较紧密规则。(2)与正常对照组相比,自发性高血压大鼠模型组皮层锥体细胞结构稀疏紊乱,并存在细胞空泡,排列疏松不均,形态不规则,且细胞数量减少(P0.05),细胞空染或淡染。与模型组相比,Ses 80mg/kg和160mg/kg剂量组及Cap组的细胞空染程度有相应程度的减少,且神经元排列较紧密规则,组织结构较为紧密。(3)(1)与WKY组相比,SHR组海马T-AOC降低(P0.05)。与SHR组相比,Ses高剂量组和Cap组均有不同程度的上升(P0.05)。(2)与WKY组相比,SHR组皮层T-AOC显著降低(P0.01)。与SHR组相比,Ses高、低剂量组和Cap组均有不同程度的上升(P0.05或P0.01)。(3)与WKY组相比,SHR组海马中过氧化氢含量升高(P0.05)。与SHR组相比,Ses高剂量组和Cap组均有不同程度的下降(P0.05或P0.01)。(4)与WKY组相比,SHR组皮层中过氧化氢含量升高(P0.05)。与SHR组相比,Ses 160mg/kg组和Cap组均有不同程度的下降(P0.05或P0.01)。(4)(1)与WKY组相比,SHR组海马中SOD含量下降(P0.05)。与SHR组相比,Ses高、低剂量组和Cap组均有不同程度的上升(P0.05或P0.01)。(2)与WKY组相比,SHR组皮层中SOD含量明显下降(P0.01)。与SHR组相比,Ses高、低剂量组和Cap组均有不同程度的上升(P0.05或P0.01)。(3)与WKY组相比,SHR组海马中MDA水平升高(P0.05)。与SHR组相比,Ses高剂量组和Cap组均有不同程度的下降(P0.05)。(4)与WKY组相比,SHR组皮层中MDA水平明显升高(P0.01)。与SHR组相比,Ses高、低剂量组和Cap组均有不同程度的下降(P0.05或P0.01)。(5)(1)与WKY组相比,SHR组海马中NO含量上升(P0.05)。与SHR组相比,Ses 160mg/kg组和Cap组均有不同程度的下降(P0.05)。(2)与WKY组相比,SHR组皮层中NO含量上升(P0.05)。与SHR组相比,Ses160mg/kg组和Cap组均有不同程度的下降(P0.05)。(6)(1)与WKY组相比,SHR组大鼠各个区n NOS阳性神经细胞表达均明显上升,AIOD值明显增高(P0.01)。与SHR组相比,用药组大鼠各区n NOS阳性神经细胞表达均明显下降,且以DG区最为明显,其Ses高、低剂量组和Cap组n NOS阳性神经细胞表达均有不同程度的下降(P0.05或P0.01),AIOD值下降(P0.01或P0.05);与SHR组相比,CA1、CA2和CA3三个区的Ses 160mg/kg剂量组和Cap组n NOS阳性神经细胞表达均有不同程度的下降(P0.05或P0.01),AIOD值下降(P0.01或P0.05)。(2)与WKY组相比,SHR组大鼠皮层n NOS阳性神经细胞表达均明显上升,AIOD值明显增高(P0.01),与模型组相比,Ses 160mg/kg剂量组和Cap组大鼠皮层n NOS阳性神经细胞表达均明显下降(P0.01),AIOD值明显下降(P0.01)。(7)(1)与WKY组相比,SHR组海马中n NOS蛋白表达明显升高(P0.01)。与SHR组相比,Ses高剂量组和Cap组n NOS蛋白表达均有显著下降(P0.01)。(2)与WKY组相比,SHR组皮层中n NOS蛋白表达明显升高(P0.01)。与SHR组相比,Ses高、低剂量组和Cap组n NOS蛋白表达均明显下降(P0.01)。(8)(1)与WKY组相比,SHR组海马中p47phox蛋白表达明显升高(P0.01)。与SHR组相比,Ses高剂量组和Cap组p47phox蛋白表达均有显著下降(P0.01)。(2)与WKY组相比,SHR组皮层中p47phox蛋白表达明显升高(P0.01)。与SHR组相比,Ses高、低剂量组和Cap组n NOS蛋白表达均有不同程度的下降(P0.05或P0.01)。(3)与WKY组相比,SHR组海马中p22phox蛋白表达明显升高(P0.01)。与SHR组相比,Ses高、低剂量组和Cap组n NOS蛋白表达均有不同程度的下降(P0.05或P0.01)。(4)与WKY组相比,SHR组皮层中p22phox蛋白表达明显升高(P0.01)。与SHR组相比,Ses高剂量组和Cap组p22phox蛋白表达均有显著下降(P0.01)。结论:(1)芝麻素可以有效的降低SHR血压,改善脑部海马、皮层部位神经元病理损伤。(2)芝麻素可改善海马、皮层部位的氧化应激,其机制可能是通过降低H2O2水平,提高T-AOC水平并升高海马、皮层部位SOD含量,降低海马、皮层部位MDA含量;降低海马、皮层部位NO含量;下调海马、皮层部位n NOS及p22phox、p47phox的蛋白表达并抑制它们所介导的氧化应激损伤,进而对高血压大鼠海马、皮层部位的氧化应激起到改善作用。
[Abstract]:Objective : To investigate the mechanism of sesamin to improve the oxidative stress in hippocampus and cortex of spontaneously hypertensive rats . SHR was divided into four groups : Ses high dose ( 160 mg / kg / day , n = 10 ) , low dose of Ses ( 80 mg / kg / day , n = 10 ) , positive Cap ( 30 mg / kg / d , n = 10 ) and SHR ( 0.5 % sodium carboxymethyl cellulose 5 ml / kg / d , n = 10 ) . Results : ( 1 ) Compared with the control group , the levels of SOD and MDA in hippocampus and cortex were significantly decreased ( P0.05 or P0.01 ) . Compared with the control group , the levels of NOS , NADPH oxidase subunit p22phox and p47phox in hippocampus , cortex and hippocampus were measured by colorimetry and ABTS method . ( 2 ) Compared with the WKY group , the content of SOD in the hippocampus of SHR group decreased ( P0.05 or P0.01 ) . Compared with the SHR group , the levels of SOD in the hippocampus of SHR group were significantly decreased ( P0.05 or P0.01 ) . Compared with the SHR group , the expression of NO in the cortex of SHR group increased significantly ( P0.05 ) . Compared with the SHR group , the expression of NO in the SHR group decreased significantly ( P0.05 or P0.01 ) . Compared with the SHR group , the expression of NO in the hippocampus of SHR group decreased significantly ( P0.05 or P0.01 ) . Compared with WKY group , the expression of p47phox protein in SHR group significantly decreased ( P0.01 ) . Compared with WKY group , the expression of p47phox protein in SHR group was significantly decreased ( P0.01 ) . Compared with SHR group , the expression of p47phox protein in SHR group decreased significantly ( P0.01 ) . Compared with WKY group , the expression of p22phox protein in the cortex of SHR was significantly increased ( P0.01 ) . Conclusion : ( 1 ) The expression of p22phox protein in the high dose group and Cap group decreased significantly ( P0.01 ) .
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R259

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