替米沙坦对糖尿病高血压大鼠肾内小动脉重构的影响  

Remodeling of intrarenal small arteries in rats with diabetic hypertension and influence of telmisartan on the remodeling

作　　者：黄鑫涛 洪华山[2] 李小红 李鸿雁 闫晓景 李之恒 李中原 

机构地区：[1]河南省驻马店市中心医院心血管内二科,驻马店460000 [2]福建医科大学附属协和医院干部病房科

出　　处：《中国循证心血管医学杂志》2015年第6期821-826,共6页Chinese Journal of Evidence-Based Cardiovascular Medicine

摘　　要：目的探讨糖尿病高血压大鼠（DSHR）的肾内小动脉（IRSAS）的重构及替米沙坦对IRSAs重构的影响。方法40只12周白发性高血压大鼠（SHR）随机分成4组，SHR对照组、DSHR组、高剂量治疗组、低剂量治疗组，每组10只。同时20只12周龄、性别配对的京都威斯特（WKY）大鼠随机分2组，一组为正常对照组（WKY组），一组制成DWKY组，各组均为10只。低剂量治疗组、高剂量治疗组为SHR雄性大鼠STZ建模后，分别给予替米沙坦灌胃。其余仅给予蒸馏水灌胃。DSHR组及DWKY组仅注射链脲佐菌素（STZ）建模。8周后终止实验。取左侧肾脏经苏木素-伊红（HE）、苦味酸-天狼猩红（Sirius-red）、弹力纤维和胶原纤维双重染色（P／VB法），IRSAs按血管外径大小分20-49μm组、50～99μm组、100-200μm组，计算机辅助成像系统计算各组IRSAs血管壁面积（WA）、血管壁厚（WT）、血管腔径（ID）及壁腔比（WT／ID）。各组切片以α-平滑肌肌动蛋白（α-SMA）、鼠抗人巨噬细胞单克隆抗体（ED1）、Ⅲ型胶原（COLⅢ）抗体免疫组化染色，ED1阳性细胞计数，COLⅢ光密度IOD比较。原位末端标记（TUNEL）检测IRSAs血管壁细胞凋亡、增殖细胞核抗原PCNA免疫组化评估IRSAs血管壁细胞增殖，分别计算凋亡指数（AI）和增殖指数（PI）。结果①与WKY组比较，DWKY组血管WT增加，ID明显减小，差异有统计学意义（P均〈0．05）。外径50—99μm组与100—200μm组的IRSAs重构相似，但50—99μm组WT／ID增加更为显著。与DWKY组和SHR组比较，DSHRWT、WA、WT／ID均升高，差异有统计学意义（P均〈0．05）。替米沙坦干预8周，高剂量治疗组和低剂量治疗组WT、WT／ID及WA均较DSHR组明显改善，差异有统计学意义（P均〈0．05）。②SHR组和DWKY组血管PCNA阳性率比WKY组增高；与DSHR组比较，高剂量治疗组和低剂量治疗组PI均显著降低，但二者阳性差�Objective To investigate the remodeling of intrarenal small arteries （IRSAs） in diabetic spontaneous hypertension rats （DSHR）, and the influence of telmisartan on IRSAs remodeling. Methods Male SHR rats （12 weeks old, n=40） were randomly divided into SHR group, DSHR group, high-dose group and low-dose group （each n=10）, and at the same time, WKY rats （12 weeks old, n=20） were randomly divided into normal control group （WKY group） and diabetic WKY group （DWKY group, each n=10）. The low-dose group and high-dose group were intragastrically given telmisartan, and other groups were intragastrically given distilled water after model establishment with STZ. IRSAs were divided, according to external diameters of vessels, into 20 μ m-49 μm group （20-49 group）, 50 μ m-99 μm group （50-99 group） and 100 μm-200 μm group （100-200 group）. The wall area （WA）, wall thickness （WT） and internal diameter （ID） of IRSAs and ratio of WT to ID （WT/ID） were calculated by using computer-assisted image analysis system in all groups. IRSAs sections were stained with α -SMA, ED1 and COLⅢ immunohistochemistry technique for counting ED1 positive ceils and comparing integrated optical density （IOD） of COLⅢ in all groups. The wall cell apoptosis of IRSAs was detected by using TUNEL, wall cell proliferating of IRSAs was reviewed by using PCNA immunohistochemistry technique, and apoptosis index （AI） and proliferating index （PI） were calculated respectively. Results ①Compared with WKY group, WT increased, ID decreased significantly （all P〈0.05）. IRSAs remodeling was similar in 50-99 group and 100-200 group, but increased more significantly in 50-99 group. Compared with DWKY group and SHR group, WT, WA and WT/ID increased （all P〈0.05） in DSHR group. After telmisartan intervention for 8 w, WT, WT/ID and WA were improved significantly in high-dose group and low-dose group compared with DSHR group （all P〈0.05）. ②The positive rate of PCNA increased in SH

关 键 词：糖尿病性高血压 肾内小动脉 血管重构 平滑肌细胞 替米沙坦 大鼠 

分 类 号：R587.1[医药卫生—内分泌]