医学RS阻断剂对糖尿病大鼠早期动脉粥样硬化形成影响.docVIP

RAS阻断剂对糖尿病大鼠早期动脉粥样硬化形成影响 作者：高伟 陈作元 王修卫 李玉山 【摘要】 目的 观察血管紧张素转换酶抑制剂贝那普利(Bena)和血管紧张素Ⅱ 1 型受体拮抗剂厄贝沙坦（Irbe）对2型糖尿病（DM）大鼠早期动脉粥样硬化形成的影响, 并探讨其可能的机制。方法将40只雄性SD大鼠随机分为正常对照(NC) 组、DM组、Bena组和Irbe组，每组10只。 以喂高糖高脂饮食方法建立SD大鼠DM模型，DM组、Bena组、Irbe组给予高糖高脂饮食1个月后腹腔注射25 mg/kg链脲佐菌素；NC组给予普通饮食，注射枸橼酸缓冲液作为对照。在此基础上，Bena组给予Bena 3 mg/（kg·d）灌胃，Irbe组给予Irbe 20 mg/（kg·d）灌胃，NC组、DM组给予生理盐水灌胃。16周后测定各组大鼠总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDLC)水平与稳态血糖（BG）、稳态胰岛素（PGI）浓度， 用酶联免疫法检测血清脂联素（APN）浓度， 用免疫组化法检测主动脉血管壁核转录因子(NFκB) 及血管细胞黏附分子1 (VCAM1) 表达水平。结果 DM组、Bena组和Irbe组TC、TG、LDLC与BG水平较NC组均显著升高(F=6.18～182.56，q=3.49～28.36，Plt;0.01)，但3组间各指标比较差异无显著性(Pgt;0.05)。 Bena组和Irbe组血清APN浓度显著高于DM组(F=65.11，q=7.37、9.41,Plt;0.01),NFκB、VCAM1 表达水平和浸润的单核细胞数明显低于DM 组(F=37.64～255.33，q=6.01～22.41，Plt;0.01), Bena组和Irbe组主动脉内皮损伤明显轻于DM 组。而Bena组和Irbe组各检测指标比较差异无显著性（Pgt;0.05）。结论 Bena 和Irbe能升高DM大鼠血清APN浓度,抑制其血管壁NFκB 活化、VCAM1表达和单核细胞浸润,防止早期动脉粥样硬化形成。 【关键词】 糖尿病,2型;动脉硬化;贝那普利;厄贝沙坦 ［ABSTRACT］ Objective To observe the effect of benazepril and irbesartan on early atherogenesis in rats with diabetes mellitus (DM) and explore its mechanism. Methods Forty male SD rats were equally randomized to four groups: control group (NC), DM group, Benazepril (Bena) group and Irbesartan (Irbe) group. High fat and high glucose diet were used to establish a DM rat model. The rats in DM, Bena, and Irbe groups were fed with highglucose and high fat diet for one month, then streptozotocin (25 mg/kg) was injected intraperitoneally, to those in NC group, full diet was offered and citrate buffer was injected. Benazepril, 3 mg/(kg·d), for Bena; Irbesartan, 20 mg/(kg·d), for Irbe; and normal saline for NC, all the medicine were given through intragastric administration for above three groups. TC, TG, LDLC, BG and PGI were measured. The serum adiponectin level was measured using enzymelinked immunosorbent assay (ELISA). Immunohistochemistry was used to analyze the expressions of NFκB and VCAM1 in aortic wall. Results The levels of TC, TG, LDLC and BG in DM, Bena and Irbe groups w