RhoA/ROCK通路在糖尿病大鼠心肌纤维化形成中的作用研究  

The role of RhoA/ROCK pathway in the formation of myocardial fibrosis in diabetic rats

作　　者：张黎明[1] 肖婧[1] 

机构地区：[1]襄阳市中心医院内分泌科,湖北襄阳441021

出　　处：《临床和实验医学杂志》2017年第11期1048-1050,共3页Journal of Clinical and Experimental Medicine

摘　　要：目的探讨Rho A/ROCK通路在糖尿病大鼠心肌纤维化形成中的作用。方法选取清洁级雌性SD大鼠30只建立糖尿病大鼠模型,按随机数字表法分为法舒地尔组和模型组,分别给予盐酸法舒尔地尔注射液(10 mg/kg/d)和等体积生理盐水腹腔注射,再选择10只大鼠作为对照组予普通饲料喂养。24周末测量各组大鼠心脏重量、体重、心脏组织形态和心肌胶原沉积程度,测定各组心肌匀浆超氧化物歧化酶(SOD)和丙二醛(MDA),采用Western blot法检测心肌磷酸化肌球蛋白磷酸酯酶靶点亚单位1(p MYPT1)。结果模型组体重低于对照组,而心脏重量和心脏重量/体重比明显高于对照组(P<0.05);法舒地尔组体重较模型组有所上升,而心脏体重和心脏重量/体重比下降(P<0.05);模型组大鼠心肌细胞排列混乱,结构不清晰,间质中成纤维细胞增多,法舒地尔组大鼠心肌间质中成纤维细胞较模型组减少;模型组心肌间质及血管周围胶原面积为(11.34±0.74)%,心肌胶原含量为3.55±0.13 g/mg,明显较对照组增高(P<0.05);法舒地尔组胶原面积和胶原含量分别为(3.32±0.32)%和(2.35±0.18)g/mg,均较模型组降低(P<0.05);模型组心肌MDA和p-MYPT1为(2.60±0.34)nmol/mgprot和0.933±0.021,明显高于对照组(P<0.05);法舒地尔组MDA和p-MYPT1分别为(1.30±0.41)nmol/mgprot和0.501±0.017,均较模型组降低(P<0.05);模型组SOD为(174.01±17.35)U/mgprot,明显低于对照组(P<0.05),而法舒地尔组SOD为(195.23±11.28)U/mgprot,较模型组有所升高(P<0.05)。结论 Rho A/ROCK通路在糖尿病大鼠心肌纤维化中起了重要作用,ROCK抑制剂法舒地尔能有效抑制糖尿病心肌纤维化。Objective To investigate the role of RhoA/ROCK pathway in the formation of myocardial fibrosis in diabetic rats. Methods 30 SD rats which were turn into diabetic model were randomly divided into fasudil group and model group, hydrochloric acid fasudil injection （10 mg/kg/d） and equal volume normal saline were given respectively. 10 rats were selected as control group which fed with normal diet. Heart weight, body weight, the morphology of cardiac tissue, the degree of myocardial collagen deposition were measured after 24 weeks later. Superox-ide dismutase （SOD） and malondialdehyde （MDA） of myocardial homogenate were determined in all groups. Western blot method was used to d-tect phosphorylation of myosin phosphatase target subunit 1 （ pMYPTl） in cardiac muscle. Results The weight of model group was lower than that of control group, while the heart weight and heart weight/body weight were significantly higher than that of control group （ P 〈 0. 0 5 ） . Fasud-il group weight increased compared to model group and heart weight, heart weight/body weight declined compared to diabetic group （ P 〈 0. 05 ）. In model group, the cardiac muscle cells arranged in disorder, the structure was not clear and fibroblast cells increased. Fasudil group myocardial interstitial fibroblasts decreased compared to model group. Myocardial interstitial and perivascular collagen area of model group was （11.34 ±0. 74） % . The content of myocardial collagen was （3. 55 ± 0. 13） g/mg which were significantly higher than control group （ P 〈 0. 05 ） . Collagen area and collagen content of fasudil group were （3. 32 ± 0. 32） % and （2. 35 ±0.18） g/mg which decreased compared to diabetic group （ P 〈0. 05 ）. MDA and p - MYPT1 of model group were （2. 60 ± 0. 34） nmol/mgprot and 0.933 ± 0. 021 which were significantly higher than that of control group （ P 〈0.05 ）. MDA and MYPT1 of fasudil group were （1.30 ±0.41） nmol/mgprot and 0.501 ±0.017 which decreased compared to model g

关 键 词：大鼠 糖尿病 RhoA/ROCK通路 心肌纤维化 法舒地尔 

分 类 号：R542.2[医药卫生—心血管疾病] R587.2[医药卫生—内科学]