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卡托普利与坎地沙坦对1型糖尿病小鼠肺动脉结构及功能的影响

International Journal of Respiration(2022)

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Abstract
目的:探究血管紧张素转化酶抑制剂卡托普利(CAP)和血管紧张素Ⅱ受体拮抗剂坎地沙坦(CAD)对链脲佐菌素诱导的1型糖尿病(T1DM)小鼠模型中肺动脉病理形态学、血管张力、舒张功能和氧化应激水平的影响。方法:本研究为实验研究。选用6~8周龄雄性C57BL/6J小鼠,使用简单随机分组法分为T1DM模型组和正常对照(NC)组,模型组采用腹腔注射链脲佐菌素的方法造模。将成模小鼠使用简单随机分组法分为T1DM组、T1DM+CAP组和T1DM+CAD组,对后两组使用灌胃手法给予CAP(100 mg·kg -1·d -1,4 d)和CAD(100 mg·kg -1·d -1,4 d)。检测4组小鼠的血糖、体质量变化,对肺动脉进行HE染色、Masson染色及超氧化物阴离子荧光探针染色,测定肺动脉血管张力和舒张能力。 结果:4组小鼠第7天体质量比较差异有统计学意义( F=138.97, P<0.001),与NC组比较,T1DM组、T1DM+CAP组和T1DM+CAD组体质量均降低,差异均有统计学意义( P值均<0.05)。T1DM组、T1DM+CAP组和T1DM+CAD组小鼠血糖在注射STZ第4天血糖值超过11.0 mmol/L,提示T1DM模型造模成功。4组小鼠第7天血糖比较差异有统计学意义( F=21.55, P<0.001),与NC组比较,T1DM组、T1DM+CAP组和T1DM+CAD组血糖均升高,差异均有统计学意义( P值均<0.05)。4组1、10 μmol/L NE刺激下的肺动脉血管张力比较差异均有统计学意义( F值分别为8.84、14.36, P值均<0.05)。与T1DM组比较,1 μmol/L NE刺激下其余3组的肺动脉血管张力高,10 μmol/L NE刺激下其余3组的肺动脉血管张力低,差异均有统计学意义( P值均<0.05)。与T1DM组(42.67%±3.06%)比较,NC组肺动脉血管舒张比例(80.50%±5.51%)高;T1DM+CAP组(54.71%±4.56%)和T1DM+CAD组(70.07%±10.00%)的舒张比例低,差异均有统计学意义( P值均<0.05)。 结论:链脲佐菌素引起的T1DM可引起小鼠肺动脉结构损伤和功能紊乱,表现为管壁增厚、胶原纤维含量增加,氧化应激水平增强,收缩和舒张功能受损。CAP和CAD可能通过降低肺动脉氧化应激水平对糖尿病小鼠的肺动脉起到保护作用。
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Diabetes mellitus, type 1,Mice,Streptozotocin,Reactive oxygen species,Vascular ring tension
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