贝那普利和厄贝沙坦对糖尿病大鼠早期血管病变影响

目的观察血管紧张素转换酶抑制剂（ACEI）贝那普利和血管紧张素Ⅱ（AngⅡ）1型受体拮抗剂厄贝沙坦对2型糖尿病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40只雄性SD大鼠随机分为正常对照组（A组）、2型糖尿病组（B组）、贝那普利组（C组）和厄贝沙坦组（D组）,每组10只。以高糖高脂饮食方法建立SD大鼠糖尿病模型,16周后测定总胆固醇（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;采用免疫组化法检测主动脉血管壁核转录因子（NF-κB）及细胞间黏附分子-1（ICAM-1）表达水平。结果B、C、D组TC、TG、LDL-C与BG水平较A组显著升高（F=6.18～182.56,q=3.49～28.36,P〈0.01）,但B、C、D组TC、TG、LDL-C与BG水平差异无显著意义（P〉0.05）。C、D组主动脉血管壁NF-κB及ICAM-1表达水平和浸润的单核细胞数明显少于B组（F=37.64～217.33,q=6.01～22.41,P〈0.01）,主动脉内皮损伤程度明显轻于B组。结论贝那普利和厄贝沙坦能抑制2型糖尿病大鼠血管壁NF-κB活化、ICAM-1表达和单核细胞浸润,可防止早期动脉粥样硬化形成。

EFFECTS OF BENAZEPRIL AND IRBESARTAN ON EARLY VASCULOPATHY IN RATS WITH DIABETES MELLITUS

Objective To observe the effects of benazepril and irbesartan on early vascular lesion in rats with diabetes mellitus （DM） and explore its possible mechanism. Methods Forty male SD rats were evenly randomized to control group （group A）, DM group （B）, benazepril group （C） and irbesartan group （D）. A DM model in rat was established by feeding with high glucose and high fat diet. TC, TG, LDL-C, BG and PGI were measured 16 weeks later. Immunohistochemistry was used to analyze the expression of NF-κB and ICAM-1 in the wall of aorta. Results The levels of TC, TG, LDL-C and BG in groups B, C and D were markedly increased as compared with group A （F=6.18-182.56,q=3.49-28.36,P〈0.01）, but the levels of above items between these three groups did not show statistical difference （P〉0.05）. The expressions of NF-κB and ICAM-1, and the numbers of monocyte infiltrating into the intima of the aorta in groups C and D were lower than that in group B （F=37.64- 217.33,q=6.01-22.41,P〈0.01）, and the endothelial damage of the aorta was much slighter. Conclusion Benazepril and irbesartan can prevent early atherogenesis through inhibiting NF-κB activation, ICAM-1 expression and monoeyte infilitration.