摘要
目的高血糖合并高血脂在临床心血管疾病中非常普遍,文中通过观察高血糖高血脂大鼠主动脉内皮功能和Rho激酶的表达,研究Rho激酶与内皮功能的关系及Rho激酶抑制剂对其的影响。方法健康雄性Wistar大鼠随机数字表法分成空白对照组(5只)、模型组(10只)、药物组(10只)。模型组和药物组先采用经尾静脉注射链脲佐菌素加高脂饮食制备高血糖高血脂的模型,再分别给予等渗盐水、Rho激酶抑制剂法舒地尔腹腔注射治疗4周。实验结束后测定3组大鼠血糖(VBG)、三酰甘油(TG)、血清总胆固醇(TC)、血清低密度脂蛋白胆固醇(LDL)、血清高密度脂蛋白胆固醇(HDL)、一氧化氮合酶(e NOS)、内皮素(ET-1)表达水平以及肌球蛋白磷酸酶结合亚基1(MYPT-1)和Rho激酶的mRNA表达。HE染色观察内皮形态学变化。结果与空白对照组比较,模型组VBG、ET-1、MYPT-1、ROCK和Rho A mRNA水平明显升高[(6.18±1.14)mmol/L vs(26.36±3.25)mmol/L,(72.13±6.13)pg/m L vs(88.22±4.61)pg/m L,(0.54±0.08)vs(1.28±0.17),(0.16±0.20)vs(0.83±0.12),(0.40±0.18)vs(0.78±0.13),P<0.05],TG、TC、LDL亦升高(P<0.05),e NOS水平降低[(24.42±2.13)U/L vs(17.36±1.58)U/L,P<0.05]。与模型组比较,药物组VBG[(17.70±2.69)mmol/L]、ET-1[(75.03±2.50)pg/m L]、MYPT-1(0.74±0.11)、ROCK mRNA水平(0.40±0.08)和Rho AmRNA(0.25±0.07)水平减低(P<0.05),TG[(1.56±0.14)mmol/L]、TC[(6.26±0.43)mmol/L]、LDL[(4.76±0.57)mmol/L]亦降低(P<0.05),e NOS水平[(22.83±1.60)U/L]明显升高(P<0.05)。内皮形态学变化:空白对照组大鼠主动脉内皮形态正常,模型组主动脉内皮病理损伤较重,药物组主动脉内皮损伤明显改善。结论高血糖高血脂大鼠存在内皮功能障碍和Rho激酶高表达,Rho激酶抑制剂可改善其内皮功能。
Objective Hyperglycaemia and hyperlipid are common in clinical cardiovascular disease. The article was to observe the change of endothelial and the expression of Rho-kinase in the aorta of rats with hyperglycaemia and hyperlipid and the relationship between them. Methods Healthy male Wistar rats were randomly divided into 3 groups： 5 as normal control group,10 as model group and 10 as drug intervention group. The latter two groups were given high-fat diets for 5 weeks after tail vein injection of streptozocin（ STZ） to establish hyperglycaemia and hyperlipid models,then fasudil（ inhibitor of Rho-kinases） or saline were respectively given intraperitoneally for 4 weeks. Venous blood glucose（ VBG）,blood lipid levels,ET-1 and e NOS were tested,along with the expression of MYPT-1（ the protein substrates of ROCK） 、mRNA of Rho A and ROCK. Results Compared with normal control group,the levels of VBG、ET-1、MYPT-1、mRNA of ROCK and Rho A were increased in model group[（ 6. 18 ± 1. 14） mmol / L vs（ 26. 36 ±3. 25） mmol / L,（ 72. 13 ± 6. 13） pg / m L vs（ 88. 22 ± 4. 61） pg / m L,（ 0. 54 ± 0. 08） vs（ 1. 28 ± 0. 17）,（ 0. 16 ± 0. 20） vs（ 0. 83 ±0. 12）,（ 0. 40 ± 0. 18） vs（ 0. 78 ± 0. 13）,P 0. 05]. TG、TC、LDL were also higher in model group（ P 0. 05）,while e NOS level was lower in model group than in control group[（ 24. 42 ± 2. 13） U / L vs（ 17. 36 ± 1. 58） U/L,P 0. 05]. Compared with model group,the levels of VBG[（ 17. 70 ± 2. 69） mmol/L]、TG、TC、LDL,ET-1[（ 75. 03 ± 2. 50） pg/m L]、MYPT-1（ 0. 74 ± 0. 01） 、mRNA of ROCK（ 0. 40 ± 0. 08） and Rho A（ 0. 25 ± 0. 07） in drug intervention group were lower（ P 〈0. 05）,while e NOS level（ 0. 74 ± 0. 11） was higher（ P〈 0. 05） in drug intervention group than in model group.Conclusion Endothelial dysfunction and over-expression of Rho kinase can be found in hyperglycaemia and hyperlipid rat models. Fasudil could improve endothelial function.
出处
《医学研究生学报》
CAS
北大核心
2015年第11期1138-1142,共5页
Journal of Medical Postgraduates
基金
辽宁省自然科学基金(20092109)
关键词
高血糖
高血脂
RHO激酶
内皮功能
Hyperglycaemia
Hyperlipid
Rho kinase
Endothelial Function
