盐酸纳布啡对睡眠呼吸暂停综合征大鼠模型的心肌保护作用

Myocardial protective effect of naborphine hydrochloride on sleep apnea syndrome rat model

目的研究盐酸纳布啡对睡眠呼吸暂停综合征大鼠模型的心肌保护作用。方法以间歇性低氧干预的方法建立睡眠呼吸暂停综合征大鼠模型,并随机分为模型组、实验组、对照组和联合组,每组12只;另取12只置于低压氧舱内给予常氧处理,设为空白组。对照组按20 mg·kg^(-1)的剂量灌胃给予2 mg·mL^(-1)ML385,同时尾静脉注射与实验组等剂量0.9%NaCl;实验组按3 mg·kg^(-1)的剂量尾静脉注射0.3 mg·mL^(-1)盐酸纳布啡,同时灌胃给予与对照组等剂量0.9%Na Cl;联合组按20 mg·kg^(-1)的剂量灌胃给予2 mg·mL^(-1)ML385+按3mg·kg^(-1)的剂量尾静脉注射0.3 mg·mL^(-1)盐酸纳布啡;空白组和模型组均灌胃给予与对照组等剂量0.9%Na Cl+尾静脉注射与实验组等剂量0.9%Na Cl。5组大鼠每天给药1次,连续给药14 d。用酶联免疫吸附实验法检测血清肌酸同工酶(CK-MB)和心肌肌钙蛋白Ⅰ(cTnⅠ)水平,用蛋白质印迹法检测心肌组织核因子E2相关因子2(Nrf2)和Ⅰ型血红素氧合酶(HO-1)蛋白的表达情况。结果实验组、对照组、联合组、模型组和空白组的血清CK-MB分别为(1 378.27±198.46),(5 018.18±320.31),(3 902.03±238.68),(3 721.25±246.28)和(1 320.35±130.71) U·L^(-1),cTnⅠ分别为(22.39±4.27),(119.13±24.13),(75.03±15.12),(73.48±13.36)和(21.83±3.78) ng·L^(-1),心肌组织Nrf2蛋白表达量分别为0.99±0.16,0.21±0.05,0.41±0.11,0.39±0.09和1.02±0.15,心肌组织HO-1蛋白表达量分别为0.98±0.17,0.19±0.06,0.38±0.10,0.37±0.08和1.03±0.16。实验组的上述指标与模型组和联合组比较,联合组的上述指标与对照组比较,差异均有统计学意义(均P <0.05)。结论盐酸纳布啡可通过激活Nrf2/HO-1通路,进而保护睡眠呼吸暂停综合征大鼠的心肌组织。

Objective To study the myocardial protective effect of naborphine hydrochloride on sleep apnea syndrome rat model.Methods A rat model of sleep apnea syndrome was established by intermittent hypoxia intervention,and the rats were randomly divided into model,experimental,control,combined groups with 12 rats per group.Another12 rats were placed in a hypobaric oxygen chamber and given normoxic treatment,which were set as the blank group.The control group was given 2 mg·mL^(-1) ML385 by gavage at a dose of 20 mg·kg^(-1) and the same volume of 0.9% NaCl as the experimental group was given by tail vein injection at the same time.The experimental group was given 0.3 mg·mL^(-1) nalbuphine hydrochloride by tail vein injection at a dose of 3 mg·kg^(-1) and the same volume of 0.9% NaCl as the control group by gavage.The combined group was given 2 mg·mL^(-1) ML385 by gavage at a dose of 20 mg·kg^(-1) and 0.3 mg·mL^(-1) nalbuphine hydrochloride by tail vein injection at a dose of 3 mg·kg^(-1).The blank group and model group were given the same volumes of 0.9%NaCl as the control group by gavage and the same volume of 0.9% NaCl as the experimental group by tail vein injection.The five groups were administered once a day for fourteen consecutive days.Enzyme-linked immunosorbent assay was used to detect the serum levels of creatine isoenzyme(CK-MB) and troponin Ⅰ(cTn Ⅰ).The expressions of nuclear factor E2-related factor 2(Nrf2) and hemeoxygenase-1(HO-1) protein in myocardial tissue were detected by Western blot.Results The serum levels of CK-MB of experimental,control,combined,model and blank groups were(1 378.27±198.46),(5 018.18±320.31),(3 902.03±238.68),(3 721.25±246.28) and(1 320.35±130.71) U·L^(-1),the serum levels of cTn I were(22.39±4.27),(119.13±24.13),(75.03±15.12),(73.48±13.36) and(21.83±3.78) ng·L^(-1),the expressions of Nrf2 protein were0.99±0.16,0.21±0.05,0.41±0.11,0.39±0.09 and 1.02±0.15,the protein expressions of HO-1 in myocardial tissue were 0.98±0.17,0.19±0.06,0.38±0.10,0.37±0.08 and 1.03±0.16,respectively.The above indexes of the experimental group were compared with those of model and combination groups,and those of the combination group were compared with those of control group,the differences were statistically significant(all P <0.05).Conclusion Nalorphine hydrochloride can protect the myocardial tissue of sleep apnea syndrome rats by activating Nrf2/HO-1 pathway.