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

Effects of Captopril and Candesartan on structure and function of pulmonary arteries in type 1 diabetic mice

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、10μmol/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,1μmol/L NE刺激下其余3组的肺动脉血管张力高,10μmol/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。

Objective To explore the effects of Captopril(CAP),an angiotensin converting enzyme inhibitor,and Candesartan(CAD),an angiotensinⅡreceptor antagonist,on the pathophysiology,vascular tone and diastolic function of pulmonary arteries and oxidative stress levels in Streptozotocin-induced type 1 diabetes mellitus(T1DM)model in mice.Methods This is an experimental study.Male C57BL/6J mice aged at 6-8 weeks were selected and randomly divided into T1DM model group and normal control(NC)group.The mice in model group received intraperitoneal injection of Streptozotocin for modeling.Modelled mice were randomly divided into the T1DM group,T1DM+CAP group and T1DM+CAD group.The mice in the latter two groups were given administered with CAP(100 mg·kg^(-1)·d^(-1),4 days)and CAD(100 mg·kg^(-1)·d^(-1),4 days)by gavage.The blood glucose,body weight,pulmonary artery HE staining,Masson staining and dihydroethidium staining,pulmonary artery vascular tension and diastolic ability were detected.Results The difference in the body mass of mice on the 7th day among the four groups was statistically significant(F=138.97,P<0.001).The body mass of all the mice in the T1DM group,T1DM+CAP group and T1DM+CAD group dropped compared with NC group,and the differences were statistically significant(all P<0.05).The blood glucose level of mice in the T1DM group,T1DM+CAP group and T1DM+CAD group was greater than 11.0 mmol/L on the 4th day after being injected with Streptozotocin,indicating that the T1DM modeling was successfully established.The difference in the blood glucose of mice on the 7th day among the four groups was statistically significant(F=21.55,P<0.001),the blood glucose of all the mice in the T1DM group,T1DM+CAP group and the T1DM+CAD group increased when compared with NC group,the differences were statistically significant(all P<0.05).The differences in the pulmonary artery vascular tension under the stimulation of 1μmol/L and 10μmol/L NE in the four groups were statistically significant(F were8.84,14.36,all P<0.05,respectively).The pulmonary artery vascular tension of the mice in the other three groups was high under the stimulation of 1μmol/L NE when compared with T1DM group.The pulmonary artery vascular tension of the other three groups under the stimulation of 10μmol/L NE was low,and the differences were statistically significant(all P<0.05).The diastolic percent of pulmonary arteries of mice in the NC group(80.50%±5.51%)was higher;and such index of mice in the T1DM+CAP group(54.71%±4.56%)and T1DM+CAD group(70.07%±10.00%)was lower when compared with T1DM group(42.67%±3.06%),and the differences were statistically significant(all P<0.05).Conclusions Streptozotocin-induced T1DM can cause mouse pulmonary artery structural damage and functional disorder,being characterized by wall thickening,increased collagen fiber content,enhanced oxidative stress level and impaired systolic and diastolic function.CAP and CAD is capable of protecting pulmonary arteries of diabetes mice by reducing the pulmonary artery oxidative stress level.