红景天苷调控炎症反应及氧化应激机制对慢性间歇性缺氧大鼠心功能的保护作用

Protective effects of salidroside on cardiac function in rats with chronic intermittent hypoxia by regulating inflammatory response and oxidative stress

目的探讨红景天苷调控炎症反应及氧化应激机制对慢性间歇性缺氧(CIH)大鼠心功能的保护作用。方法选取成年健康雄性SD大鼠30只,按照随机数字表法分为对照组、模型组及观察组,各10只。对照组大鼠自然环境条件下饲养,每天定时予0.9%氯化钠注射液灌胃;模型组大鼠慢性间歇性缺氧造模后,每天定时予0.9%氯化钠注射液灌胃;观察组大鼠慢性间歇性缺氧造模后,每天定时予红景天苷溶液+0.9%氯化钠注射液灌胃,均连续饲养4周。4周后,检测大鼠的左心室功能,采用酶联免疫吸附试验法检测血清肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平,采用丙二醛和超氧化物歧化酶(SOD)试剂盒检测心脏组织中丙二醛和SOD水平。采用流式细胞仪检测大鼠心肌细胞凋亡率,通过蛋白质印迹法检测B细胞淋巴瘤2(Blc-2)、Bcl-2相关X蛋白(Bax)及半胱氨酸天冬氨酸蛋白酶3表达量。结果模型组大鼠左心室射血分数(LVEF)低于对照组、左心室收缩末期内径(LVESD)大于对照组[(49±4)%比(76±10)%、(6.8±1.0)mm比(3.6±0.5)mm],而观察组LVEF[(60±7)%]高于模型组、LVESD[(5.4±0.8)mm]小于模型组,差异均有统计学意义(均P<0.05)。模型组和观察组血清TNF-α、IL-6水平均高于对照组[(56±13)、(25±8)ng/L比(15±4)ng/L,(66±13)、(26±8)ng/L比(16±4)ng/L],但观察组均低于模型组,差异均有统计学意义(均P<0.05)。模型组心脏组织中丙二醛水平高于对照组、SOD水平低于对照组,而观察组丙二醛水平低于模型组、SOD水平高于模型组,差异均有统计学意义(均P<0.05)。模型组、观察组心肌细胞凋亡率均高于对照组,但观察组低于模型组,差异均有统计学意义(均P<0.05)。模型组、观察组心脏组织中Blc-2表达量低于对照组,但观察组高于模型组,模型组、观察组Bax和半胱氨酸天冬氨酸蛋白酶3表达量均高于对照组,但观察组均低于模型组,差异均有统计学意义(均P<0.05)。结论红景天苷通过调控炎症反应、氧化应激机制及细胞凋亡分子表达来保护CIH大鼠的心功能。

Objective To explore the protective effects of salidroside on cardiac function in rats with chronic intermittent hypoxia(CIH)by regulating inflammatory response and oxidative stress.Methods Totally 30 healthy adult male SD rats were randomly divided into control group,model group and observation group,with 10 rats in each group.The control group was fed under natural environmental conditions and given 0.9%sodium chloride injection by gavage regularly every day.After CIH modeling,the model group was given 0.9%sodium chloride injection by gavage regularly every day,and the observation group was given salidroside+0.9%sodium chloride injection by gavage regularly every day and then administered by gavage for 4 weeks.After 4 weeks,the left ventricular function was detected.Enzyme linked immunosorbent assay was used to analyzed the serum levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).The levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in cardiac tissue were detected by MDA and SOD kits.The apoptosis rate of rat cardiomyocytes was detected by flow cytometry,and the expressions of B-cell lymphoma 2(Bcl-2),Bcl-2 associated X protein(Bax)and Caspase-3 in cardiac tissue were detected by western blotting.Results The left ventricular ejection fraction(LVEF)of model group was lower than that in control group,left ventricular end systolic diameter(LVESD)was greater than that in control group[(49±4)%vs(76±10)%,(6.8±1.0)mm vs(3.6±0.5)mm],while LVEF[(60±7)%]in observation group was higher than that in model group and LVESD[(5.4±0.8)mm]was less than that in model group(all P<0.05).Levels of TNF-αand interleukin-6 in serum in model group and observation group were higher than those in control group[(56±13),(25±8)ng/L vs(15±4)ng/L;(66±13),(26±8)ng/L vs(16±4)ng/L],while the levels in observation group were lower than those in model group(all P<0.05).The level of MDA in cardiac tissue in model group was higher than that in control group,the level of SOD was lower than that in control group,while the level of MDA in observation group was lower than that in model group,and the level of SOD was higher than that in model group(all P<0.05).Cardiomyocyte apoptosis rate in model group and observation group was higher than that in control group,while the rate in observation group was lower than that in model group(all P<0.05).The expression of Bcl-2 in model group and observation group was lower than that in control group,while the level in observation group was higher than that in model group;the expressions of Bax and Caspase-3 in model group and observation group were higher than those in control group,while the levels in observation group were lower than those in model group(all P<0.05).Conclusion Salidroside can protect the cardiac function of CIH rats by inhibiting inflammatory reaction,oxidative stress and apoptosis molecules expressions.